The DOI matches its Crossref record; 150 of the 150 references it cites were found in a registry or an index; none of the 187 sources its claims cite is checked for support yet.
Antioxidant Protective Mechanisms against Reactive Oxygen Species (ROS) Generated by Mitochondrial P450 Systems in Steroidogenic Cells
Abstract
Mitochondrial P450 type enzymes catalyze central steps in steroid biosynthesis, including cholesterol conversion to pregnenolone, 11beta and 18 hydroxylation in glucocorticoid and mineralocorticoid synthesis, C-27 hydroxylation of bile acids, and 1alpha and 24 hydroxylation of 25-OH-vitamin D. These monooxygenase reactions depend on electron transfer from NADPH via FAD adrenodoxin reductase and 2Fe-2S adrenodoxin. These systems can function as a futile NADPH oxidase, oxidizing NADPH in absence of substrate, and leak electrons via adrenodoxin and P450 to O(2), producing superoxide and other reactive oxygen species (ROS). The degree of uncoupling depends on the P450 and steroid substrate. Studies with purified proteins and overexpression in cultured cells show consistently that adrenodoxin, but not reductase, is responsible for ROS production that can lead to apoptosis. In the ovary and corpus luteum, antioxidant enzyme activities superoxide dismutase, catalase, and glutathione peroxidase parallel steroidogenesis. Antioxidant beta-carotene, alpha-tocopherol, and ascorbate can protect against oxidative damages of P450 systems. In testis Leydig cells, steroidogenesis is associated with aging of the steroidogenic capacity.
Overview
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Written from the paper’s full text.
TL;DR
This review synthesizes evidence that mitochondrial P450 systems in steroidogenic cells can leak electrons to O₂, generating ROS, with adrenodoxin as a key mediator and P450c11 more uncoupled than P450scc. It describes antioxidant defenses—SOD, catalase, glutathione peroxidase, ascorbate, tocopherol, and β-carotene—that parallel steroidogenesis and can protect against oxidative damage.
Key findings
- Reconstituted bovine mitochondrial P450 components act as a futile NADPH oxidase: AdR alone had O₂ reduction <0.001 mol e⁻/min/mol AdR, but AdR + adrenodoxin increased to 149 ± 34, and AdR + adrenodoxin + P450scc increased further to 721 ± 125 mol e⁻/min/mol AdR.
- P450c11 is much more leaky than P450scc: in reconstituted systems, at most 15% of total electron flow in the P450scc system went to ROS formation, whereas 32–43% of electrons were consumed in ROS generation by P450c11.
- Adrenodoxin, not adrenodoxin reductase, appears responsible for ROS production leading to apoptosis: overexpression of human or bovine adrenodoxin decreased cell viability in all 11 cell lines tested, while an apo-mutant adrenodoxin (C46S) lacking the 2Fe-2S cluster did not cause apoptosis; AdR overexpression alone did not increase ROS or apoptosis.
- Antioxidant enzyme activities parallel steroidogenesis: in bovine corpora lutea, SOD and catalase activities peak at about day 16 of the estrous cycle and then drop in parallel with P450scc and adrenodoxin levels; ascorbate concentrations are highest in steroidogenic tissues such as adrenal cortex and corpus luteum.
Methods
- Narrative review of published studies on mitochondrial P450 systems, ROS generation, and antioxidant protection in steroidogenic cells.
- Evidence reviewed includes reconstituted systems with purified bovine mitochondrial P450 proteins, cultured-cell overexpression experiments, and animal tissue studies of adrenal cortex, ovary/corpus luteum, and testis Leydig cells.
- Main analysis is qualitative synthesis, supported by tables of electron-transfer rates, redox potentials, steroid effects on P450c11 leakage, and antioxidant levels in steroidogenic tissues.
Limitations
- The paper states that its summary points apply to the specific cases reviewed and “do not represent general rules for all mitochondrial P450 and antioxidant combinations in different systems.”
- The paper notes that there is currently no precise information on absolute concentrations of NADH and NADPH in the mitochondrial matrix where steroidogenic enzymes are located.
- Evident from the text: this is a narrative review without a systematic search or meta-analysis, and it compares findings across different species, tissues, temperatures, and cell models; the paper also acknowledges that adrenodoxin overexpression conclusions may be questioned because those studies used non-steroidogenic cells.
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Claims the paper makes
141 Not checked yet · 46 Own interpretation · 10 No basis given
None of the sources cited for this claim have been checked yet.
In the paper
“Studies with purified proteins and overexpression in cultured cells show consistently that adrenodoxin, but not reductase, is responsible for ROS production”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
- Not checked yetcites Rapoport et al., 1995
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Addition of adrenodoxin greatly stimulates the rate of NADPH oxidation and O 2 reduction.”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, even if these P450 systems leak electrons at a low rate, their total capacity for free radical generation could be high, especially in steroidogenic tissues.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“P450scc system produced less H 2 O2 during cholesterol substrate hydroxylation than that observed in the absence of substrate.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In adrenal mitochondria the concentrations of P450scc and adrenodoxin are similar”
What the sources say
- Not checked yetcites Hanukoglu and Hanukoglu, 1986
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In the paper
“ESR assays using a spin trap and other assays provided further evidence that leaking electrons react with O 2 to produce superoxide radical”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These systems can function as a futile NADPH oxidase, oxidizing NADPH in absence of substrate”
- Also stated in: § Studies with Purified Enzymes · plain
“Experiments using purified mitochondrial P450 system proteins showed that these systems can oxidize NADPH in the absence of a steroid substrate”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Studies with Purified Enzymes · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the difference between the leakage rates of these P450s would be further magnified at 37 ° C reactions for P450c11.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, P450c11 system produced more H 2 O2 during substrate deoxycorticosterone metabolism”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Addition of either of these P450s increases superoxide production significantly above that observed by reductase and adrenodoxin couple”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“While in the P450scc system at most 15% of the total electron flow was directed to ROS formation”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The degree of uncoupling depends on the P450 and steroid substrate.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and leak electrons via adrenodoxin and P450 to O 2 , producing superoxide and other reactive oxygen species (ROS).”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“These monooxygenase reactions depend on electron transfer from NADPH via FAD adrenodoxin reductase and 2Fe-2S adrenodoxin.”
What the sources say
- Not checked yetcites Grinberg et al., 2000
- Not checked yetcites Ziegler et al., 1999
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“2. Leakage stimulatory products or analogs: C-19 and C-21 steroids with an 11 β -hydroxy and a 3-keto group and 4-ene double bond that do not appear to be a substrate for P450c11. Examples: 11 β -OH-testosterone, corticosterone, progesterone, and cortisol.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In a system with this molar ratio of the two proteins, electrons appeared to leak mainly through P450scc and not through adrenodoxin”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“in the P450c11 system 32-43% of the electrons were consumed in ROS generation”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“1. Leakage stimulatory substrates: C-21 steroids with a 3-keto group and 4-ene double bond. Examples: Deoxycortisol, deoxycorticosterone.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These results overall indicated that P450c11 catalyzed steroid hydroxylation is poorly coupled relative to the P450scc activity.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, reductase-adrenodoxin couple functions as a strong futile NADPH oxidase”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the absence of its substrate cholesterol, P450scc has been observed to be more active than adrenodoxin in reducing O 2 to superoxide, with a maximal effect at a much lower concentration (0.3 μ M vs. >7 μ M for adrenodoxin)”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In other words, the coupling of the P450scc system was greater during cholesterol metabolism”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In steroidogenic tissues, the concentrations of the mitochondrial P450 system components are as much as 10 times higher than other electron transfer chain enzymes, and microsomal P450s”
What the sources say
- Not checked yetcites Hanukoglu and Hanukoglu, 1986
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The product of P450scc, pregnenolone, had no stimulatory effect on futile NADPH oxidation by the P450scc system.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Depletion of O 2 in solution using glucose oxidase revealed that O 2 is the acceptor of the leaking electrons”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Analyses of the steroid effects on P450c11 reactions (Rapoport et al., 1995) show that steroids can be classified into four groups based on their effects and their structures”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the effects of the products in stimulating ROS production by P450c11 should not be a major problem in normal physiology.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Only in the presence of adrenodoxin AdR serves as a conduit for electrons coming from NADPH (Hanukoglu et al., 1993).”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This structural specificity of the steroids in inactivation of P450c11 in cultured cells is identical to that observed in stimulation of electron leakage from P450c11 in reconstituted systems (Table 4).”
What the sources say
- Not checked yetcites Table 4
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Overexpression of an apo-mutant of adrenodoxin (C46S) that does not have the iron-sulfur (2Fe-2S) cluster essential for electron transfer did not cause apoptosis (Derouet-Humbert et al., 2005).”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
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In the paper
“An early step in this process is the release of cytochrome c from within the inter-membrane space of the mitochondria.”
What the sources say
- Not checked yetcites Bras et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The studies reviewed previously establish that mitochondrial P450 systems produce ROS.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Overexpression of human CYP11A1 that encodes P450scc showed variable effects in 11 cell lines,”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
plaincorrelationaln = 11- Asserted: passes — The authors put it forward as true.
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In the paper
“These findings are consistent with the observation that P450c11 is much more leaky than P450scc in reconstituted systems (Rapoport et al., 1995).”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies in cultured cells show similar differences.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The results of their studies showed that overexpression of either human or bovine adrenodoxin led to a decrease in cell viability in all cell lines tested.”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
plaindirectn = 11- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, apparently endogenously expressed AdR was sufficient to allow overly-expressed adrenodoxin to function as a source of ROS in transfected cells.”
hedgeddirectn = 11- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: AdR is ubiquitously expressed in different cells.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the inactivation of P450c11 in cultured cells may directly result from its much greater propensity to generate harmful oxygen radicals.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The studies reviewed previously showed that mitochondrial P450 systems reconstituted with purified proteins can generate reactive oxygen species.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The transfer of cholesterol from the cytoplasmic vesicles to the mitochondria is tightly regulated by trophic hormone stimulated mechanisms that involve steroidogenic acute regulatory protein (StAR) in most steroidogenic cells (Jefcoate, 2002; Niswender, 2002; Strauss et al., 2003).”
What the sources say
- Not checked yetcites Jefcoate, 2002
- Not checked yetcites Niswender, 2002
- Not checked yetcites Strauss et al., 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and stable or transient overexpression of AdR did not decrease cell viability in different cell lines (Derouet-Humbert et al., 2005).”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“4. Steroids without an effect: C-19 steroids without a 3-keto group or 4-ene double bond. Examples: 5 α -androstane-3 β ,17 β -diol, 5 α -androstanedione, and 4-androstene-3 β ,17 β -diol.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies in cultured cells, reviewed in the following paragraphs, reveal major similarities between the behavior of the mitochondrial P450 system proteins in reconstituted systems and within cells in culture.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The next section on the regulation of NADPH in the mitochondria of steroidogenic cells concludes that NADPH supply is not tightly linked to steroid biosynthesis.”
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Studies using purified enzymes showed major differences in the capacity of different mitochondrial P450s to generate and be affected by ROS (see previous sections).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Formation of ROS within mitochondria is one of the major internal triggers for apoptotic cell death (Bras et al., 2005).”
What the sources say
- Not checked yetcites Bras et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, 11 α -hydroxylated steroids or 11-ketosteroids did not affect 11 β -hydroxylase activity (Hornsby, 1980).”
What the sources say
- Not checked yetcites Hornsby, 1980
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The substrate cholesterol apparently stabilizes P450scc-O 2 complex, saving it for reduction by the second electron (Hanukoglu et al., 1993).”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“P450c11 is more susceptible to degradation during NADPH-dependent lipid peroxidation in bovine adrenal cortex mitochondria (Klimek et al., 1983).”
What the sources say
- Not checked yetcites Klimek et al., 1983
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In order to function as an 'electron gun,' adrenodoxin is dependent on adrenodoxin reductase (AdR) to receive reducing equivalents from NADPH, which are then donated to O 2 (Hanukoglu et al., 1993).”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“According to the in vitro studies, if NADPH is constantly available to the mitochondrial P450 systems then these oxidize NADPH in a futile cycle, generating harmful oxyradicals without coupling to steroid metabolism.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, induction of AdR expression failed to show any effect on cell proliferation (Liu and Chen, 2002),”
What the sources say
- Not checked yetcites Liu and Chen, 2002
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“3. Leakage inhibitory steroids: C-19 and C-21 steroids with an 11 α -hydroxy or an 11-keto group, a 3-keto group and 4-ene double bond. Examples: 11 α -OH-testosterone and 11 α -OH-cortisol.”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, production of ROS by mitochondrial P450 systems in steroidogenic cells appears to be an inevitable phenomenon.”
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“The half-life of P450c11 in cultured adrenocortical cells is drastically shortened by substrates of P450c11 or 11 β -hydroxylated steroids, including products of P450c11 (Hornsby, 1980).”
What the sources say
- Not checked yetcites Hornsby, 1980
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The stereospecificity of the effects in both systems (e.g., harmless 11 α -OH-testosterone vs. harmful 11 β -OH-testosterone) establish unequivocally that the results in cultured cells are specifically a result of the interaction of the steroids with the enzyme P450c11 itself, stimulating production of ROS by P450c11 during the process of electron transfer.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As noted previously, AdR by itself does not significantly oxidize NADPH.”
What the sources say
- Not checked yetcites Hanukoglu et al., 1993
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In cultured adrenocortical cells the activity of P450c11 decreases rapidly as a result of oxidative damage (Hornsby and Crivello, 1983; Hornsby, 1980, 1989).”
What the sources say
- Not checked yetcites Hornsby and Crivello, 1983
- Not checked yetcites Hornsby, 1980, 1989
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In contrast, the substrates of P450c11 stimulate the autooxidation of P450c11-O 2 complex, releasing superoxide.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This control experiment further strengthens the conclusion that the cause of apoptosis is the superoxide production by adrenodoxin.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies established that the supply of NADPH can be enhanced to meet the demands of trophic hormone stimulated steroidogenesis.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ACTH was shown to induce the expression of mitochondrial mRNAs encoding subunits of oxidative phosphorylation system enzymes, in parallel with the induction of steroidogenic enzyme genes in adrenocortical cells in culture (Raikhinstein and Hanukoglu, 1993, 1994).”
What the sources say
- Not checked yetcites Raikhinstein and Hanukoglu, 1993, 1994
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An important conclusion that can be derived from the adrenodoxin overexpression studies reviewed previously is that, apparently NADPH in the mitochondrial matrix is directly being oxidized by the AdR-adrenodoxin couple even in the absence of a P450 that could receive the electrons channeled via adrenodoxin.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A study that examined the redox state of adrenodoxin by ESR spectroscopy concluded that adrenodoxin remains fully reduced in hypophysectomized rat adrenals with or without ACTH treatment (Williams-Smith et al., 1976).”
What the sources say
- Not checked yetcites Williams-Smith et al., 1976
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Combining the previous observations, the general strategy of NADPH regulation in mitochondria appears to be maintenance of low basal levels that are augmented in bursts in response to steroidogenic trigger signals initiated by trophic hormones.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In other words, NADPH supply does not appear to be a rate-limiting factor for the AdR-adrenodoxin couple to function as an artificial NADPH oxidase generated by the adrenodoxin overexpression.”
hedged- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In bovine adrenal cortex cells in culture, P450c11, but not P450scc, undergoes rapid degradation in the absence of antioxidants and this degradation can be prevented by the addition of ascorbic acid and α -tocopherol (Hanukoglu et al., 1990a; Hornsby et al., 1985; Hornsby, 1989).”
What the sources say
- Not checked yetcites Hanukoglu et al., 1990a
- Not checked yetcites Hornsby et al., 1985
- Not checked yetcites Hornsby, 1989
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The major source of free radicals, such as superoxide and other types of ROS, in the cell, is the electron transfer reactions of the mitochondrial oxidative phosphorylation chain (Andreyev et al., 2005; Turrens, 2003).”
What the sources say
- Not checked yetcites Andreyev et al., 2005
- Not checked yetcites Turrens, 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The intra-mitochondrial levels of NADPH are co-regulated with NADH generated by the Krebs cycle, fatty acid β -oxidation and other redox reactions inside the mitochondria.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the consistent effect of adrenodoxin overexpression in 11 different cell types probably reflects a general status.”
hedged- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Mitochondrial P450 system electron transfer proteins are ubiquitously expressed in different tissues.
In the paper
“The requirement for antioxidants for P450c11 stability (but not for P450scc) in cultured cells is consistent with the observations in reconstituted systems that P450c11 leaks electrons much more than P450scc (Rapoport et al., 1995).”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The studies reviewed previously have indicated that in steroidogenic tissues, the mitochondrial P450 systems can represent an additional burden over the common oxidative stress of the respiratory chain.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Studies in reconstituted systems for both P450scc and P450c11 demonstrated that the magnitude of electron leak from these systems depends on the concentration of NADPH even in the micromolar range (Rapoport et al., 1995).”
What the sources say
- Not checked yetcites Rapoport et al., 1995
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Mn-SOD is induced by ACTH in bovine adrenocortical cells (Chinn et al., 2002).”
What the sources say
- Not checked yetcites Chinn et al., 2002
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“NADPH that supplies electrons to the mitochondrial P450 systems may be generated by several alternative routes (Hanukoglu and Rapoport, 1995).”
What the sources say
- Not checked yetcites Hanukoglu and Rapoport, 1995
hedged- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The enzyme nicotinamide nucleotide transhydrogenase catalyzes the interconversion of NADH and NADPH according to the reaction (Hatefi and Yamaguchi, 1996; Jackson, 2003):”
What the sources say
- Not checked yetcites Hatefi and Yamaguchi, 1996
- Not checked yetcites Jackson, 2003
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, continuous maintenance of a basal level of NADPH in the mitochondrial matrix is essential for normal function.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, because of its coupling to the proton electrochemical gradient across the inner mitochondrial membrane, the transhydrogenase activity (consequently NADPH production) is linked to the functioning of oxidative phosphorylation chain.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In mouse ovary, the activities of isocitrate dehydrogenase and other enzymes of glucose metabolism vary in parallel with the steroidogenic capacity of the ovary (Chapman et al., 1992).”
What the sources say
- Not checked yetcites Chapman et al., 1992
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In rat adrenals, measurement of the total SOD activity and the activity of the mitochondrial manganese superoxide dismutase (Mn-SOD) indicated that Mn-SOD encoded by the SOD2 gene accounts for all the SOD activity (Raza et al., 2005).”
What the sources say
- Not checked yetcites Raza et al., 2005
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In steroidogenic cells, the supply of cholesterol to mitochondria can be tightly coupled with trophic hormonal signals, because the supplied cholesterol is uniquely used in steroid biosynthesis.”
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In addition to their function as antioxidants, molecules such as ascorbic acid and β -carotene fulfill biological roles independent of interaction with oxygen radicals.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“ACTH administration, together with antioxidant vitamin E or DMSO, inhibited ACTH induction of Mn-SOD (Suwa et al., 2000).”
What the sources say
- Not checked yetcites Suwa et al., 2000
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recent findings indicate that mitochondrial ROS activate a mitochondrion-to-nucleus signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-kappaB transcription factor, leading to induction of SOD2 expression (Storz et al., 2005).”
What the sources say
- Not checked yetcites Storz et al., 2005
hedgeddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In bovine adrenal cortex cells in culture, P450c11, but not P450scc, undergoes rapid degradation in the absence of antioxidants and this degradation can be prevented by the addition of ascorbic acid and α -tocopherol (Hanukoglu et al., 1990a; Hornsby et al., 1985; Hornsby, 1989).”
What the sources say
- Not checked yetcites Hanukoglu et al., 1990a
- Not checked yetcites Hornsby et al., 1985
- Not checked yetcites Hornsby, 1989
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In contrast to cholesterol, the delivery of NADPH cannot be uniquely coupled to steroid hormone biosynthesis because, in addition to serving as an electron donor for P450 systems, NADPH is also used by a multitude of reactions within the mitochondria (Berger et al., 2004; Di Lisa and Ziegler, 2001; Hanukoglu and Rapoport, 1995; Hoek and Rydstrom, 1988; Kirsch and De Groot, 2001).”
What the sources say
- Not checked yetcites Berger et al., 2004
- Not checked yetcites Di Lisa and Ziegler, 2001
- Not checked yetcites Hanukoglu and Rapoport, 1995
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, even in the presence of low levels of NADPH the systems would be expected to leak electrons.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This enzyme also functions as a proton pump in the inner mitochondrial membrane.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The ROS generated by the respiratory chain can damage proteins, lipids, and DNA.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“To prevent the harmful effects of ROS, mitochondria have a rich repertoire of enzymes (e.g., manganese superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase, and glutathione reductase) and small antioxidant molecules (e.g., ascorbic acid, α -tocopherol, β -carotene) that can neutralize or scavenge superoxide and other ROS (Andreyev et al., 2005).”
What the sources say
- Not checked yetcites Andreyev et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“The induced decrease in CYP11B2 mRNA level was recovered with co-administration of vitamin E or DMSO possibly through their antioxidant actions (Suwa et al., 2000).”
What the sources say
- Not checked yetcites Suwa et al., 2000
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“There are several lines of evidence that these changes, but especially damage to the mitochondrial DNA (mtDNA), are responsible for the process of aging (Barja, 2004; Melov, 2004; Vina et al., 2005).”
What the sources say
- Not checked yetcites Barja, 2004
- Not checked yetcites Melov, 2004
- Not checked yetcites Vina et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Studies using single cell fluorimetric technique revealed that in rat adrenal glomerulosa cells, angiotensin II and cytoplasmic signal Ca 2+ evoke an increase in the level of reduced mitochondrial pyridine nucleotides (Spat and Hunyady, 2004; Spat and Pitter, 2004).”
What the sources say
- Not checked yetcites Spat and Hunyady, 2004
- Not checked yetcites Spat and Pitter, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, steroidogenic tissues would be expected to have a strong dependence on antioxidants as a defense mechanism.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, the studies reviewed next indicate that the normal function of steroidogenic tissues is dependent on antioxidants.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, retinoid derivatives of β -carotene regulate gene transcription in cells by binding to nuclear retinoid receptor (Lane and Bailey, 2005).”
What the sources say
- Not checked yetcites Lane and Bailey, 2005
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Ascorbate depletion prevents aldosterone stimulation by sodium deficiency in the guinea pig (Redmann et al., 1995).”
What the sources say
- Not checked yetcites Redmann et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings emphasize the role of Mn-SOD in coping with ROS generated in the mitochondria.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Studies in reconstituted systems using purified proteins do not provide evidence for the involvement of exogenous ROS in the biosynthetic reactions catalyzed by the mitochondrial P450s.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Prolactin that functions as a luteotropic hormone in the rat also stimulates Cu-Zn-SOD and Mn-SOD mRNA expression in rat luteal cells (Sugino et al., 1998).”
What the sources say
- Not checked yetcites Sugino et al., 1998
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“In rat luteal cells, stimulation with luteinizing hormone (LH) or luteolytic factor, prostaglandin (PG) F 2 α rapidly causes depletion of ascorbic acid (Musicki et al., 1996).”
What the sources say
- Not checked yetcites Musicki et al., 1996
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Pretreatment of the culture with antioxidants, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT), drastically reduced lipid hyperperoxide production (Crivello, 1988).”
What the sources say
- Not checked yetcites Crivello, 1988
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, superoxide production is probably stimulated by LH, as a side-reaction, a sbyproduct, of the LH stimulation of steroidogenesis.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, LH probably enhances NADPH levels in luteal cells.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There are several independent lines of evidence that trophic hormones that are involved in the stimulation of corpus luteum steroidogenesis are also involved in inducing antioxidant enzymes.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, in the guinea pig adrenal cortex, actions of ascorbate were shown to be related to the mitochondrial tocopherol content in the different zones of the cortex (Staats and Colby, 1989).”
What the sources say
- Not checked yetcites Staats and Colby, 1989
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Treatment of rat corpus luteum cells with LH that stimulates progesterone secretion has been observed also to increase superoxide generation in a dose-dependent manner (Sawada and Carlson, 1996).”
What the sources say
- Not checked yetcites Sawada and Carlson, 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Determination of the activities of the antioxidant enzymes, SOD and catalase, showed that these are correlated with the plasma progesterone levels during the bovine estrus cycle (Rapoport et al., 1998).”
What the sources say
- Not checked yetcites Rapoport et al., 1998
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As a consequence of LHstimulated steroidogenesis, superoxide production would be expected to increase as well.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In Chinese hamster ovary cells, overexpression of mitochondrial peroxiredoxin 5 showed significant protective effect on mtDNA against lesions caused by exogenously added hydrogen peroxide (Banmeyer et al., 2005).”
What the sources say
- Not checked yetcites Banmeyer et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the initial phase of development and cell proliferation with enhanced progesterone synthesis, ROS generated by the mitochondrial P450scc system represent a harmful byproduct of steroidogenesis.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“On the contrary, exogenous ROS are detrimental to the function of the P450 system proteins.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“An important action of ascorbate as an antioxidant is the recycling of α -tocopheryl radical (Buettner, 1993; May, 1999; Rose and Bode, 1993).”
What the sources say
- Not checked yetcites Buettner, 1993
- Not checked yetcites May, 1999
- Not checked yetcites Rose and Bode, 1993
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reactive oxygen species (ROS) and antioxidants appear to have two contrasting effects in the development and regression of the corpus luteum.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, as a defense against these ROS, antioxidants would be expected to rise in parallel with the steroidogenic capacity of the cells.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In bovine corpora lutea, the activities of SOD and catalase rise and reach a peak at about day 16 of the cycle and then drop in parallel with the levels of P450scc and adrenodoxin (Rapoport et al., 1998).”
What the sources say
- Not checked yetcites Rapoport et al., 1998
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Lutropin (human luteinizing hormone, LH) that stimulates follicle development, ovulation, and corpus luteum formation was shown to induce SOD in rat ovary (Laloraya et al., 1988).”
What the sources say
- Not checked yetcites Laloraya et al., 1988
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Similarly, in cultured luteal cells, high levels of superoxide are associated with inhibition of progesterone secretion (Sawada and Carlson, 1996).”
What the sources say
- Not checked yetcites Sawada and Carlson, 1996
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“During the human menstrual cycle, the activity of Mn-SOD, as well as the levels of its mRNA, were shown to increase during late luteal phase, indicating that increased enzyme activity is a result of enhanced expression of the SOD2 gene (Sugino et al., 2000).”
What the sources say
- Not checked yetcites Sugino et al., 2000
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Among the small molecule antioxidants, ascorbate is present at highest concentrations in corpora lutea, similar to the high levels observed in the adrenal cortex (Table 5).”
What the sources say
- Not checked yetcites Table 5
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The addition of an antioxidant drug, silibinin, at a low dose, potentiated ACTH-stimulated secretion of corticosteroids in hyperplastic adrenocortical cells, leading the authors to conclude that the effect of silibinin is presumably due to the antioxidant property of the drug (Racz et al., 1990).”
What the sources say
- Not checked yetcites Racz et al., 1990
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The final stage of corpus luteum regression is characterized by a decrease in the levels of the P450scc system proteins (Devoto et al., 2002; Hanukoglu, 1992; Rapoport et al., 1998; Rodgers et al., 1987).”
What the sources say
- Not checked yetcites Devoto et al., 2002
- Not checked yetcites Hanukoglu, 1992
- Not checked yetcites Rapoport et al., 1998
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In bovine kidney proximal tubule cells in primary culture, mitochondrial vitamin D hydroxylase activities were found to be inversely proportional to the increase in mitochondrial membrane lipid hyperperoxide production (Crivello, 1988).”
What the sources say
- Not checked yetcites Crivello, 1988
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Among all organs in the body, the concentration of ascorbic acid is highest in the steroidogenic tissues, adrenal cortex, and corpus luteum (Hornig, 1975; Mahan et al., 2004; Rapoport et al., 1998).”
What the sources say
- Not checked yetcites Hornig, 1975
- Not checked yetcites Mahan et al., 2004
- Not checked yetcites Rapoport et al., 1998
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The in vitro effect of β -carotene most probably reflects the function of the antioxidants to prevent oxidative damage in situ as well.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In the corpus luteum of the pseudopregnant rat, acute treatment with PGF 2 α decreased luteal vitamin C levels coincident with transient lipid peroxidation and a fall in serum progesterone levels (Aten et al., 1992).”
What the sources say
- Not checked yetcites Aten et al., 1992
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Compared to control rats of the same age, the testosterone production capacity of the rats that had the long-term suppression was higher (Chen and Zirkin, 1999).”
What the sources say
- Not checked yetcites Chen and Zirkin, 1999
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The expression of some antioxidant enzymes are activated by trophic hormones that stimulate steroidogenesis.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Examination of 43 corpora lutea from non-pregnant cows representing four stages of the ovarian cycle showed that β -carotene and α -tocopherol continuously increased from stage I to stage IV (Schweigert, 2003).”
What the sources say
- Not checked yetcites Schweigert, 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Depletion of specific antioxidants can lead to loss of activity of 'sensitive' mitochondrial P450s.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In rats, testosterone treatment for 8 days decreased catalase, glutathione peroxidase, and glutathione transferase activities in the interstitial tissue (Peltola et al., 1996).”
What the sources say
- Not checked yetcites Peltola et al., 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Similar to the findings in adrenocortical cells (see previous sections), culturing Leydig cells with vitamin E, or administering vitamin E to rats, showed protective effects on steroidogenic function (Chen et al., 2005).”
What the sources say
- Not checked yetcites Chen et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest differential sensitivity of different parts of the steroidogenic machinery to ROS effects.”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Addition of antioxidants can prevent or reverse oxidative damage effects induced by the P450 system proteins.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased activity or expression of adrenodoxin or mitochondrial P450s is associated with increased ROS production and oxidative damage.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Two other studies have independently reported that bovine corpus luteum β -carotene levels are positively correlated with plasma progesterone levels (Haliloglu et al., 2002; Rapoport et al., 1998).”
What the sources say
- Not checked yetcites Haliloglu et al., 2002
- Not checked yetcites Rapoport et al., 1998
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“As in other steroidogenic tissues, testis has the usual complement of antioxidant enzymes, including SOD, catalase, glutathione peroxidase, and glutathione transferase (Kukucka and Misra, 1993; Peltola et al., 1996)”
What the sources say
- Not checked yetcites Kukucka and Misra, 1993
- Not checked yetcites Peltola et al., 1996
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“As in the ovary, stimulation of the testicular interstitial tissue increases the activities of antioxidant enzyme glutathione peroxidase (Peltola et al., 1996).”
What the sources say
- Not checked yetcites Peltola et al., 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In rat granulosa cells in culture, gonadotropic hormone FSH and insulin-like growth factor I (IGF-I) stimulate uptake of ascorbic acid (Behrman et al., 1996).”
What the sources say
- Not checked yetcites Behrman et al., 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Studies in bovine luteal cells in culture showed that β -carotene depletion caused inactivation of P450scc and its crosslinking to adrenodoxin.”
What the sources say
- Not checked yetcites Young et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Similar to the findings in adrenocortical cells (see previous sections), culturing Leydig cells with vitamin E, or administering vitamin E to rats, showed protective effects on steroidogenic function (Chen et al., 2005).”
What the sources say
- Not checked yetcites Chen et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Steroidogenic capacity correlates with the levels of antioxidant enzymes.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Thus, after removal of the blockade, the testis started functioning at the levels observed for young rats.”
What the sources say
- Not checked yetcites Chen and Zirkin, 1999
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 33
- Probably not a substantial claim. 26
None of the sources cited for this claim have been checked yet.
In the paper
“In aerobic solution, adrenodoxin reductase that is reduced by NADPH remains reduced and does not readily oxidize by itself”
What the sources say
- Not checked yetcites Chu and Kimura, 1973
- Not checked yetcites Hanukoglu et al., 1993
- Not checked yetcites Sugiyama et al., 1979
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In contrast, 11 β -hydroxylated products of P450c11, and other steroids with a strict stereo-specificity, strongly stimulated electron leakage from P450c11, but not from P450scc”
What the sources say
- Not checked yetcites Rapoport et al., 1995
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mitochondrial P450 type enzymes catalyze central steps in steroid biosynthesis, including cholesterol conversion to pregnenolone, 11 β and 18 hydroxylation in glucocorticoid and mineralocorticoid synthesis, C-27 hydroxylation of bile acids, and 1 α and 24 hydroxylation of 25-OH-vitamin D.”
What the sources say
- Not checked yetcites Hanukoglu, 1992
- Not checked yetcites Miller, 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A study that examined ROS formation in reconstituted mitochondrial P450 systems revealed that both P450scc and P450c11 generate ROS during their catalytic function of steroid hydroxylation”
What the sources say
- Not checked yetcites Rapoport et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Adrenodoxin expression enhanced oxidation of dihydroethidium to ethidium, providing evidence for the generation of ROS in the cell lines.”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
plaindirectn = 11- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In steroidogenic cells there are no major vesicular stores of steroid products, as steroids are rapidly secreted into the blood stream after synthesis.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Cytochrome c aggregates with apoptosis-protease-activating factor 1 (Apaf-1), and procaspase-9 forming apoptosomes. Caspase-9 is cleaved and activated by the apoptosomes and then it activates downstream effector caspases (caspase-3 and -7), spreading a cascade of proteolytic activity that leads to digestion of structural proteins in the cytoplasm and eventual phagocytosis of the cell (Bras et al.”
What the sources say
- Not checked yetcites Bras et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The first step of steroid hormone biosynthesis in all steroidogenic tissues is the cleavage of the side-chain of cholesterol by P450scc that produces pregnenolone (Hanukoglu, 1992; Miller, 2005; Payne and Hales, 2004).”
What the sources say
- Not checked yetcites Hanukoglu, 1992
- Not checked yetcites Miller, 2005
- Not checked yetcites Payne and Hales, 2004
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The addition of this steroid derivative induces apoptosis in human breast cancer MCF-7 cells by disruption of mitochondrial function, associated with cytochrome c release, and production of reactive oxygen species (Narvaez and Welsh, 2001; Narvaez et al., 2003).”
What the sources say
- Not checked yetcites Narvaez and Welsh, 2001
- Not checked yetcites Narvaez et al., 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, experimental observations noted previously raise a caveat that steroidal drugs may have similar effects stimulating ROS production by steroid metabolizing enzymes.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Consistent with these findings, AdR over-expression by itself is not associated with increased ROS formation or ROS triggered apoptosis (Derouet-Humbert et al., 2005).”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In other P450 systems, various substrates and substrate analogs show wide variation in their effects on the coupling of the electron transfer process”
What the sources say
- Not checked yetcites Jung et al., 2002
- Not checked yetcites Shertzer et al., 2004a, 2004b
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Consistent with the process of apoptosis, overexpression of adrenodoxin was shown to disrupt mitochondrial transmembrane potential, indicating breakdown of the outer mitochondrial membrane and increased caspase activity in the cell (Derouet-Humbert et al., 2005).”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The steroids that have no effect on electron leakage may not enter into the substrate pocket of P450, or simply not affect the heme-O 2 interaction in the active site.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“leading the authors to conclude that 'difference in the availability of mitochondrial cholesterol might contribute to the observed tissue specificity of CYP11A1induced apoptosis' (Derouet-Humbert et al., 2005).”
What the sources say
- Not checked yetcites Derouet-Humbert et al., 2005
hedgedconditionaln = 11- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The loss of the activity of P450c11 is not accompanied by loss of steroid synthesis, indicating that P450scc continues to function with little or no damage under the same conditions.”
What the sources say
- Not checked yetcites Hornsby and Crivello, 1983
- Not checked yetcites Hornsby, 1980, 1989
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While cholesterol supply is regulated by 'on-off' switch type mechanisms, NADPH synthesis is regulated by mechanisms that function as a graded rheostat.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In bovine corpora lutea, a low but significant correlation was observed between mitochondrial P450 system enzymes and a cytochrome oxidase subunit (Hanukoglu and Hanukoglu, 1986).”
What the sources say
- Not checked yetcites Hanukoglu and Hanukoglu, 1986
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The rate of mitochondrial ROS generation is related to the level of oxidative damage to mtDNA and is inversely correlated with maximum longevity in higher vertebrates (Barja, 2004).”
What the sources say
- Not checked yetcites Barja, 2004
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the placenta, a different START protein (MLN64) is involved in the transport of cholesterol to the mitochondria (Tuckey, 2005).”
What the sources say
- Not checked yetcites Tuckey, 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If these findings reflect normal physiological status, then adrenodoxin may be a source of ROS in absence of steroid metabolism.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Cellular metabolism could have changed within minutes after induction of anesthesia and prior to removal of the adrenal.
None of the sources cited for this claim have been checked yet.
In the paper
“Chronic in vivo administration of ACTH in rats was observed to reduce plasma aldosterone, down-regulate CYP11B2 mRNA, and reduce P450aldo activity (Lehoux et al., 1998; Suwa et al., 2000).”
What the sources say
- Not checked yetcites Lehoux et al., 1998
- Not checked yetcites Suwa et al., 2000
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chronic ACTH administration in rats increased Mn-SOD expression, but decreased glutathione peroxidase mRNA in the adrenal capsules (Raza et al., 2005; Suwa et al., 2000).”
What the sources say
- Not checked yetcites Raza et al., 2005
- Not checked yetcites Suwa et al., 2000
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In sheep corpora lutea, cytosolic Cu-Zn-SOD, mitochondrial Mn-SOD, and glutathione peroxidase activities rise while nitric oxide synthase (NOS) decreases during the luteal phase (Al-Gubory et al., 2005).”
What the sources say
- Not checked yetcites Al-Gubory et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The addition of an antioxidant drug, silibinin, at a low dose, potentiated ACTH-stimulated secretion of corticosteroids in hyperplastic adrenocortical cells, leading the authors to conclude that the effect of silibinin is presumably due to the antioxidant property of the drug (Racz et al., 1990).”
What the sources say
- Not checked yetcites Racz et al., 1990
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, at the stage of luteolysis, free radicals could play a functional role in apoptotic cell death and contribute to regression of corpus luteum (Behrman et al., 2001; Foyouzi et al., 2005; Niswender et al., 2000).”
What the sources say
- Not checked yetcites Behrman et al., 2001
- Not checked yetcites Foyouzi et al., 2005
- Not checked yetcites Niswender et al., 2000
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In cultured ovarian cancer cells, ROS stress induced Mn-SOD expression; suppression of Mn-SOD expression by siRNA caused an increase in superoxide and promoted cell proliferation in vitro and tumor growth in vivo (Hu et al., 2005).”
What the sources say
- Not checked yetcites Hu et al., 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“During the luteal phase, the increase in progesterone secretion reflects proliferation of steroidogenic cells and a major increase in the expression of the steroidogenic enzymes, primarily mitochondrial cholesterol side-chain cleavage P450scc.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In rats, vitamin A depletion causes a secondary deficiency of ascorbic acid in the adrenal, leading to adrenocortical degeneration, and ascorbate supplement prevents degeneration (Gruber et al., 1976).”
What the sources say
- Not checked yetcites Gruber et al., 1976
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ACTH stimulated cortisol secretion from the guinea pig adrenal is accompanied by a decrease in the levels of ascorbate in the adrenal, but not in other tissues or plasma (Laney et al., 1990).”
What the sources say
- Not checked yetcites Laney et al., 1990
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“If there is no pregnancy, then corpus luteum regresses by an apoptotic process (McCracken et al., 1999; Niswender, 2002; Tilly, 1996; Zheng et al., 1994).”
What the sources say
- Not checked yetcites McCracken et al., 1999
- Not checked yetcites Niswender, 2002
- Not checked yetcites Tilly, 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, at the final stage of corpus luteum, antioxidant levels would be expected to decrease, allowing ROS to contribute to apoptosis and regression of the corpus luteum.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The findings for the small antioxidant molecules show that the levels of these antioxidants change significantly during corpus luteum development, yet there does not appear to be a consistent pattern indicating complex functional and regulatory roles for these.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The findings reviewed in the following paragraphs for the antioxidant enzymes SOD, catalase, and glutathione peroxidase are, in general, consistent with these expected trends.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, while Cu-Zn-SOD activity and mRNA dropped during luteal regression, Mn-SOD activity and mRNA showed further increases, suggesting that these two enzymes play different roles in regulating luteal function (Sugino et al., 2000).”
What the sources say
- Not checked yetcites Sugino et al., 2000
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“After ovulation, the follicle enters the luteal phase, during which granulosa and theca cells of the follicle proliferate to form corpus luteum, and synthesize and secrete progesterone at high levels (nmol/L range) to prepare the uterus for implantation.”
What the sources say
- Not checked yetcites McCracken et al., 1999
- Not checked yetcites Niswender, 2002
- Not checked yetcites Tilly, 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“In bovine corpus luteum, the levels of ascorbate increase during the luteal phase and then drop during regression (Rapoport et al., 1998).”
What the sources say
- Not checked yetcites Rapoport et al., 1998
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In rat ovary, follicular development was associated with an increase in vitamin A and luteal regression was associated with an increase in both vitamins A and E (Aten et al., 1992).”
What the sources say
- Not checked yetcites Aten et al., 1992
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“With aging in males, the capacity for testosterone biosynthesis declines as a consequence of multiple alterations in the hypothalamic-pituitary axis and Leydig cell steroidogenic system (Wang and Stocco, 2005; Zirkin and Chen, 2000).”
What the sources say
- Not checked yetcites Wang and Stocco, 2005
- Not checked yetcites Zirkin and Chen, 2000
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Exogenously added H 2 O2 was observed to inhibit both cAMP-stimulated progesterone production and StAR protein expression in MA-10 tumor Leydig cells, but did not effect P450scc enzyme levels (Diemer et al., 2003).”
What the sources say
- Not checked yetcites Diemer et al., 2003
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The Leydig cells develop and reach their full steroidogenic potential after puberty (Cummings and Kavlock, 2004).”
What the sources say
- Not checked yetcites Cummings and Kavlock, 2004
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Steroidogenic cells have a full spectrum of antioxidant molecules, which in some tissues reach the highest level in the body.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“| Vitamin A | Bovine | C. luteum | 3.5-5.5 μ g/g tissue | (Haliloglu et al., 2002) |”
What the sources say
- Not checked yetcites Haliloglu et al., 2002
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“| α -tocopherol | Rat | Adrenal | 30-50 μ g/g tissue | (Burczynski et al., 2001) |”
What the sources say
- Not checked yetcites Burczynski et al., 2001
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The findings of some studies provide evidence for the hypothesis that ROS produced as a by-product of steroidogenesis may be responsible for age-related decline in testosterone production by the Leydig cells (Chen and Zirkin, 1999; Zirkin and Chen, 2000).”
What the sources say
- Not checked yetcites Chen and Zirkin, 1999
- Not checked yetcites Zirkin and Chen, 2000
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“| Ascorbate | Rat | Adrenal | 2.5-5 mg/g tissue | (Mitani et al., 2005) |”
What the sources say
- Not checked yetcites Mitani et al., 2005
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Vitamin C is taken up into the cell by specific transporter proteins SVCT1 and SVCT2 (Wilson, 2005).”
What the sources say
- Not checked yetcites Wilson, 2005
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“| α -tocopherol | Bovine | C. luteum | 1-132 μ g/g tissue | (Rapoport et al., 1998) (Schweigert, 2003) |”
What the sources say
- Not checked yetcites Rapoport et al., 1998
- Not checked yetcites Schweigert, 2003
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The Leydig cells in the interstitium, located in between the seminiferous tubules of the testis, are the major source of androgenic steroids (Payne and Hales, 2004; Zirkin and Chen, 2000).”
What the sources say
- Not checked yetcites Payne and Hales, 2004
- Not checked yetcites Zirkin and Chen, 2000
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The fact that both adrenodoxin and P450 are metal carrying proteins that generate free radicals during electron transfer make these proteins prone to metal-catalyzed oxidation and crosslinking reactions (Liu et al., 2004; Stadtman, 1993).”
What the sources say
- Not checked yetcites Liu et al., 2004
- Not checked yetcites Stadtman, 1993
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“| Ascorbate | Bovine | C. luteum | 4-10 mg/g tissue | (Rapoport et al., 1998) |”
What the sources say
- Not checked yetcites Rapoport et al., 1998
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The addition of β -carotene at levels found in bovine serum, but not α -tocopherol or ascorbic acid, inhibited the cross-linking (Young et al., 1995).”
What the sources say
- Not checked yetcites Young et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“| β -carotene | Bovine | C. luteum | 6-216 μ g/g tissue | (Arikan and Rodway, 2001) (Haliloglu et al., 2002) |”
What the sources say
- Not checked yetcites Arikan and Rodway, 2001
- Not checked yetcites Haliloglu et al., 2002
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“and small antioxidants (Chen et al., 2005; Livera et al., 2002).”
What the sources say
- Not checked yetcites Chen et al., 2005
- Not checked yetcites Livera et al., 2002
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
AdR is ubiquitously expressed in different cells.
“AdR is ubiquitously expressed in different cells.”
The paper relies on this without support.
Mitochondrial P450 system electron transfer proteins are ubiquitously expressed in different tissues.
“Yet, the mitochondrial P450 system electron transfer proteins are ubiquitously expressed in different tissues.”
The paper relies on this without support.
The cells used in adrenodoxin overexpression studies are non-steroidogenic cells.
“This conclusion may be questioned, noting that the cells used in overexpression studies are non-steroidogenic cells.”
The paper relies on this without support.
Cellular metabolism could have changed within minutes after induction of anesthesia and prior to removal of the adrenal.
“This interpretation requires a caveat that cellular metabolism could have changed within minutes after induction of anesthesia and prior to the removal of the adrenal.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This electron transfer forms a high-affinity complex between the proteins17.”
From Impairing the interaction between Erg11 and cytochrome P450 reductase Ncp1 enhances azoles’ antifungal activities (2025) · cites this paper as [17]
Experimental — accuracy not yet measured
Citations
Cites
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084
Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587
Oxidative DNA damage: mechanisms, mutation, and disease
Cooke, M. S., Evans, M. D., Dizdaroglu, M., & Lunec, J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0752rev · Cited by 3,245
P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature
Nelson, D. R., Koymans, L. M. H., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., et al. (1996) · Pharmacogenetics · doi:10.1097/00008571-199602000-00002 · Cited by 2,946
The Pecking Order of Free Radicals and Antioxidants: Lipid Peroxidation, α-Tocopherol, and Ascorbate
Buettner, G. R. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1074 · Cited by 2,417 · cited 1×
“An important action of ascorbate as an antioxidant is the recycling of α-tocopheryl radical (Buettner, 1993; May, 1999; Rose and Bode, 1993).”
BackgroundOverview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones
Payne, A. H., & Hales, D. B. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0030 · Cited by 1,766
Topology of superoxide production from different sites in the mitochondrial electron transport chain
St-Pierre, J., Buckingham, J. A., Roebuck, S. J., & Brand, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207217200 · Cited by 1,545
Stadtman, E. R. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.004053 · Cited by 1,408
Mitochondrial metabolism of reactive oxygen species
Andreyev, A. Y., Kushnareva, Y. E., & Starkov, A. A. (2005) · Biochemistry (Moscow) · doi:10.1007/s10541-005-0102-7 · Cited by 1,336
Mechanisms Controlling the Function and Life Span of the Corpus Luteum
NISWENDER, G. D., Juengel, J. L., Silva, P. J., Rollyson, M. K., & McIntush, E. W. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.1.1 · Cited by 1,076
Cited by
Sorted by citations
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Snezhkina, A. V., Kudryavtseva, A. V., Kardymon, O. L., Savvateeva, M. V., Melnikova, N. V., Krasnov, G. S., & Dmitriev, A. A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6175804 · Cited by 934
Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives
Hajam, Y. A., Rani, R., Ganie, S. Y., Sheikh, T. A., Javaid, D., Qadri, S. S., Pramodh, S., Alsulimani, A., Alkhanani, M. F., Harakeh, S., et al. (2022) · Cells · doi:10.3390/cells11030552 · Cited by 915
Azad, M. B., Chen, Y., & Gibson, S. B. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2270 · Cited by 764
Metadata
- Authors
- Hanukoglu, I.
- Affiliations
- Ariel University (IL)
- Corresponding author
- Hanukoglu, Israel
- ORCID
- Hanukoglu, Israel
- Venue
- Drug Metabolism Reviews
- Publisher
- Informa UK Limited
- Published
- 2006-01
- Volume
- 38
- Issue
- 1-2
- Pages
- 171-196
- ISSN
- 0360-2532 (ISSN-L)
- 1097-9883
- OpenAlex
- W2038758189
- Semantic Scholar
- e47d7fe29aa2374a673ae5d2f21edb3fbd816884
- Cited by
- 293
- References
- 150
- Citations by year
- 2026: 15 · 2025: 16 · 2024: 18 · 2023: 18 · 2022: 14 · 2021: 20 · 2020: 16 · 2019: 10 · 2018: 11 · 2017: 17 · 2016: 12 · 2015: 13 · 2014: 18 · 2013: 11 · 2012: 22
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- mitochondrial cytochrome P450, steroidogenesis, reactive oxygen species, oxidative stress, adrenodoxin, adrenodoxin reductase, superoxide production, antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase, beta-carotene, alpha-tocopherol, vitamin C, Leydig cells, corpus luteum, ovary, steroidogenic cells
- MeSH terms
- Adrenodoxin, Animals, Antioxidants, Cytochrome P-450 Enzyme System, Electron Transport, Endocrine Glands, Humans, Mitochondria, NADP, Steroids, Reactive Oxygen Species
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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