Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

In the paper

“The damaging properties of singlet oxygen can be effectively used in photo-dynamic therapy (PDT), used for example in cancer treatment, in which singlet oxygen is formed by the light-induced excitation of a suitable photosensitizer (Gunaydin et al. 2021).”

What the sources say

• Supported

  The Therapeutic Applications section explains that light excites the photosensitizer, which then transfers energy to molecular oxygen to produce singlet oxygen. It also states that the resulting molecules can damage vital cellular components and that PDT can kill tumor cells by generating singlet oxygen. (LLM, conf=0.94)

  cites Gunaydin et al. 2021 source

In the paper

“Since the production of melatonin with age is gradually decreasing, such an event may to some extent correlate with the development of many chronic diseases (Hardeland 2012).”

What the sources say

• Supported

  Section 2 reports that the nocturnal melatonin peak regularly decreases during aging. Sections 2 and 5 link low melatonin levels with multiple diseases and suggest that deficiency might increase the likelihood of age-related diseases, while noting that direct evidence for the latter relationship remains insufficient. The citing sentence's tentative wording is consistent with those qualifications. (LLM, conf=0.90)

  cites Hardeland 2012 source

In the paper

“Vitamin C has been found to reduce the cholesterol level in patients with hypercholesterolemia (Rossig et al. 2001)”

What the sources say

• ?Could not verify

  The sections on vitamin C therapy in patients with congestive heart failure report reduced endothelial-cell apoptosis and apoptotic microparticles; the section on oxidative-stress markers reports reduced TBARS. Searches for hypercholesterolemia and cholesterol levels found no passage stating that vitamin C reduced cholesterol in patients with hypercholesterolemia. (LLM, conf=0.76)

  cites Rossig et al. 2001 sourceExperimental — accuracy not yet measured

In the paper

“ROS can oxidize MAPK and hyper-activate MAPK/ERK pro-proliferative signaling (Son et al. 2011).”

What the sources say

• Partly supported

  Section 5 (page unavailable) reports that ROS can activate the ERK pathway, and Section 3 (page unavailable) links sustained MAPK activation to possible uncontrolled proliferation. But Section 5 says the precise molecular targets of ROS are unknown; it does not establish that ROS directly oxidizes MAPK or that the ROS-induced ERK activation is necessarily pro-proliferative. (LLM, conf=0.88)

  cites Son et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“In contrast with this study, NOX4-derived hydrogen peroxide exhibited anti-atherosclerotic effects by smooth muscle cell regulation in diabetic mice (Di Marco et al. 2016; Cortinovis et al. 2022).”

What the sources say

• Supported

  The Introduction identifies NOX4 as a hydrogen peroxide-producing enzyme and describes its protective role in diabetes-associated atherosclerosis. Discussion §4.4 links NOX4-dependent hydrogen peroxide to suppression of smooth muscle cell proliferation and fibrosis—changes associated with accelerated atherosclerosis in diabetes. The study includes diabetic Apoe−/− mice and complementary smooth muscle cell experiments. (LLM, conf=0.89)

  cites Di Marco et al. 2016 source
• Not checked yetcites Cortinovis et al. 2022 source

In the paper

“SOD is another agent which, when present in the reaction mixture, diminished DNA cleavage (Nandi et al. 2019).”

What the sources say

• Not checked yetcites Nandi et al. 2019 source

In the paper

“Recent results using various cell types confirmed the “stochastic and transient” formation of superoxide radicals, termed “mitochondrial” flash from either a single or restricted clusters of interconnected mitochondria (O-Uchi et al. 2018).”

What the sources say

• Not checked yetcites O-Uchi et al. 2018

In the paper

“Interestingly, it has recently been reported that the hydroxyl radicals originating from the Fenton reaction might not be the main product when a physiological concentration of bicarbonate is present in the system (Illes et al. 2019).”

What the sources say

• Not checked yetcites Illes et al. 2019 source

In the paper

“It has been reported that ROS stimulated the oxidation of thioredoxin and its dissociation from ASK1 (Matsukawa et al. 2004).”

What the sources say

• Not checked yetcites Matsukawa et al. 2004 source

In the paper

“For example, hydrogen peroxide was able to regulate the phosphorylation of 512 and 523 tyrosine residues of protein kinase C (Aicart-Ramos et al. 2014).”

What the sources say

• Not checked yetcites Aicart-Ramos et al. 2014 source

In the paper

“The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others).”

In the paper

“A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear”

In the paper

“Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator.”

• Also stated in: § Introduction · plain

  “Oxidative stress, characterized by a shifted equilibrium between the formation and elimination of free radicals toward the formation, is a common denominator of the pathogenesis of chronic diseases and aging (Harman 1956; Valko et al. 2007).”

What the sources say

• Not checked yetcites Harman 1956 source
• Not checked yetcites Valko et al. 2007 source

In the paper

“The most frequently occurring free radicals and reactive molecules in biological systems are derived from oxygen (reactive oxygen species, ROS) and nitrogen (Reactive Nitrogen Species, RNS).”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 2015 source

In the paper

“Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress (“bad stress”).”

In the paper

“Dysregulation of peroxynitrite has been linked with cardiovascular, neurological, and cancer diseases (Gulcin 2020).”

What the sources say

• Not checked yetcites Gulcin 2020 source

In the paper

“Exogenous sources of ROS also involve the consumption of smoked meat and intake of metal-containing drugs (cyclosporine, bleomycin, gentamycin, and others) (Bhattacharyya et al. 2014).”

What the sources say

• Not checked yetcites Bhattacharyya et al. 2014 source

In the paper

“Alternatively, CO3·− can be formed via the reaction between nitric oxide, NO·, and superoxide radical anion, O2·−, forming peroxynitrite reacting further with CO2 (see Fig. 2) (Fleming and Burrows 2020; Samuni et al. 2022).”

What the sources say

• Not checked yetcites Fleming and Burrows 2020 source
• Not checked yetcites Samuni et al. 2022 source

In the paper

“A complex antioxidant defense system, including both endogenous and exogenous antioxidants, protect cells from ROS-induced toxicity (Finkel and Holbrook 2000).”

What the sources say

• Not checked yetcites Finkel and Holbrook 2000 source

In the paper

“In addition, peroxynitrite can modify proteins by nitration or oxidation of amino acids, involving cysteine, tyrosine, and methionine (Bartesaghi and Radi 2018).”

What the sources say

• Not checked yetcites Bartesaghi and Radi 2018 source

In the paper

“Damaging properties of singlet oxygen, 1O2 (both electrons paired, S = 0, multiplicity 2.S + 1 = 2.0 + 1 = 1) can be effectively used in anticancer therapy, involving photodynamic therapy (PDT) (Maharjan and Bhattarai 2022).”

What the sources say

• Not checked yetcites Maharjan and Bhattarai 2022 source

In the paper

“Since chemical bonds of biomolecules are formed by two antiparallel electrons (↑↓), their interaction (oxidation) with molecular dioxygen (containing two parallel electrons) is spin restricted and therefore rather slow.”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 2015 source

In the paper

“The superoxide anion radicals can be formed in biological systems as a consequence of thiol-mediated repair of radicals (R·) by thiols (RSH), resulting in the formation of thiyl radicals (RS·) (Valko et al. 2006)4”

What the sources say

• Not checked yetcites Valko et al. 2006 source

In the paper

“Under the conditions of disturbed redox metal homeostasis (e.g. Alzheimer’s diseases and some cancers), free (unbound) metal ions can catalyze heterolytic cleavage of hydrogen peroxide (formed by the SOD-catalyzed dismutation reaction), resulting in the formation of hydroxyl radicals (·OH) and OH−. This reaction is termed the Fenton reaction (Valko et al. 2005; Gates 1999)7”

What the sources say

• Not checked yetcites Valko et al. 2005 source
• Not checked yetcites Gates 1999 source

In the paper

“If the transfer of one oxygen to a substrate molecule escapes control mechanisms, uncoupling in the ROS formation and subsequent damage to biomolecules may occur. (Mortezaee 2018).”

What the sources say

• Not checked yetcites Mortezaee 2018 source

In the paper

“The superoxide radical is considered a primary ROS produced in mitochondria by electron leakage from the electron transport chain to molecular oxygen in the course of oxidative phosphorylation (Valko et al. 2004).”

What the sources say

• Not checked yetcites Valko et al. 2004 source

In the paper

“Cells have evolved a complex antioxidant system, formed by enzymatic antioxidants, such as superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidases (GPXs), thioredoxin (Trx) as well as low molecular antioxidants, whose concerted action is balancing the level of oxidative stress (Halliwell 2022).”

What the sources say

• Not checked yetcites Halliwell 2022 source

In the paper

“This can be explained by the fact, that superoxide radical is necessary to achieve redox cycling of metal ions (Halliwell and Gutteridge 1990).”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 1990 source

In the paper

“Drugs inducing high levels of ROS involve camptothecins, anthracyclines (doxorubicin, daunorubicin), Pt-based drugs, and others (Brezova et al. 2003).”

What the sources say

• Not checked yetcites Brezova et al. 2003 source

In the paper

“Liver diseases related to alcohol consumption are partly due to the ROS formation from ethanol (Wu and Cederbaum 2009).”

What the sources say

• Not checked yetcites Wu and Cederbaum 2009 source

In the paper

“ROS oxidize -SH groups of cysteine residues in protein kinases A, C, and D, receptor tyrosine kinase (RTK), and Ca/calmodulin independent protein kinase II, which in turn phosphorylate target proteins participating in various signaling mechanisms (Kruk et al. 2013).”

What the sources say

• Not checked yetcites Kruk et al. 2013 source

In the paper

“Some enzymes, such as superoxide dismutase, glutathione peroxidase and catalase act in a mutually supporting defense action against ROS (Krishnamurthy and Wadhwani 2012).”

What the sources say

• Not checked yetcites Krishnamurthy and Wadhwani 2012

In the paper

“Mitochondrial Ca2+ activates three dehydrogenases of the citric acid cycle resulting in increased ROS formation (Hatano et al. 2013).”

What the sources say

• Not checked yetcites Hatano et al. 2013 source

In the paper

“NF-κB translocated into the nucleus activates the transcription of target genes (Basak and Hoffmann 2008).”

What the sources say

• Not checked yetcites Basak and Hoffmann 2008 source

In the paper

“Ca2+ signaling is important in secretion, metabolism, cell survival, and death (Tarasov et al. 2012).”

What the sources say

• Not checked yetcites Tarasov et al. 2012 source

In the paper

“Low levels of ROS may oxidize the –S–S– bridges of Akt/PKB, promoting the interaction of Akt/PKB with PP2A. (Lee et al. 2002).”

What the sources say

• Not checked yetcites Lee et al. 2002

In the paper

“Ca2+-regulated extramitochondrial enzymes, such as NADPH oxidases and nitric oxide synthase (NOS) under both physiological and pathological conditions, stimulate ROS formation (Roe et al. 2013).”

What the sources say

• Not checked yetcites Roe et al. 2013 source

In the paper

“L-type channels are linked with the oxidation of thiol groups resulting in changed entry of calcium in the cytoplasm (Nishida et al. 2013).”

What the sources say

• Not checked yetcites Nishida et al. 2013 source

In the paper

“It has been confirmed that hydrogen peroxide may influence the BMK1 pathway through the direct activation of MEKK2 and MEKK3 (Zhang et al. 2016).”

What the sources say

• Not checked yetcites Zhang et al. 2016 source

In the paper

“The canonical activation pathway is triggered through the site-specific phosphorylation by an IκB-kinase (IKK) complex in response to microbes, and proinflammatory cytokines.”

What the sources say

• Not checked yetcites Basak and Hoffmann 2008 source

In the paper

“Ubiquitination plays a key role in the regulation of the NF-κB pathway (Chen and Chen 2013).”

What the sources say

• Not checked yetcites Chen and Chen 2013 source

In the paper

“As outlined above, ROS have origin from two main sources: mitochondrial oxidative metabolism and processes of cellular response to xenobiotics, bacteria, and cytokines during which ROS are formed as a part of either signal transduction pathways or a cellular defense mechanism (Finkel 2011).”

What the sources say

• Not checked yetcites Finkel 2011 source

In the paper

“Ca2+ can directly activate antioxidant enzymes such as GSH reductase and catalase and SOD through which ROS clearance is mediated (Thompson et al. 2014).”

What the sources say

• Not checked yetcites Thompson et al. 2014 source

In the paper

“GSH scavenges a wide range of ROS (·OH, H2O2, 1O2), and due to the very low value of electron reduction potential of the GSSG/GSH redox couple (EΘ = − 264 mV at pH = 7.4) is GSH able to regenerate several important antioxidants, such as radicals of vitamins E and C back to their active non-radical forms (Jones 2002) (Fig. 9).”

What the sources say

• Not checked yetcites Jones 2002 source

In the paper

“The key factor affecting the switch from antioxidant to prooxidant properties of carotenoids has been attributed to the partial pressure of oxygen, typically high in the lungs.”

What the sources say

• Not checked yetcites Young and Lowe 2001 source
• Not checked yetcites Shin et al. 2020 source

In the paper

“Excessive depletion of oxidants may result in the induction of reductive stress, characterized by declined physiological functions, such as suppressed mitochondrial function, cell proliferation, the occurrence of cardiomyopathies, and other pathologies (Rajasekaran et al. 2007).”

What the sources say

• Not checked yetcites Rajasekaran et al. 2007 source

In the paper

“The first who proposed prooxidant properties of carotenoids were Burton and Ingold (Burton and Ingold 1984).”

What the sources say

• Not checked yetcites Burton and Ingold 1984 source

In the paper

“The antioxidant properties of carotenoids are related to conjugated double bonds which can accommodate unpaired electrons and extensively delocalize them over the conjugated system of double bonds (Mortensen et al. 2001).”

What the sources say

• Not checked yetcites Mortensen et al. 2001 source

In the paper

“These two oxidized products can be reduced back to Protein-SH by the effect of GSH via the intermediate formation of S-glutathiolated protein (Protein-SSG).”

What the sources say

• Not checked yetcites Valko et al. 2006 source

In the paper

“However, under certain conditions, in the presence of free (unbound) redox metals, such as iron or copper, resulting from metal dyshomeostasis, vitamin C may exhibit prooxidant properties171819”

What the sources say

• Not checked yetcites 171819

In the paper

“Several Mn(II)-based cyclic polyamine and Mn(III) porphyrins have entered several clinical trials (Batinic-Haberle and Tome 2019).”

What the sources say

• Not checked yetcites Batinic-Haberle and Tome 2019 source

In the paper

“The most frequent involve (a) hydrogen abstraction from the carotenoid molecule, (b) electron transfer reaction, and (c) radical addition to carotenoid structure (El-Agamey et al. 2004).”

What the sources say

• Not checked yetcites El-Agamey et al. 2004 source

In the paper

“Concerning to the control group, there was an 18% increased incidence of lung cancer among those taking β-carotene supplements.”

What the sources say

• Not checked yetcites ATBC Trial 1996

In the paper

“Two thiyl radicals can combine and form a non-radical oxidized glutathione (GSSG)23”

What the sources say

• Not checked yetcites [23] source

In the paper

“Catalase plays an important role in oxidative stress-related conditions, involving inflammation, mutagenesis, and apoptosis suppression (Sandstrom and Buttke 1993).”

What the sources say

• Not checked yetcites Sandstrom and Buttke 1993 source

In the paper

“EC-SOD and glutathione peroxidase represent an important first line of defense against oxidants (Rahman and Biswas 2006).”

What the sources say

• Not checked yetcites Rahman and Biswas 2006

In the paper

“GSH scavenges a wide range of ROS (·OH, H2O2, 1O2), and due to the very low value of electron reduction potential of the GSSG/GSH redox couple (EΘ = − 264 mV at pH = 7.4) is GSH able to regenerate several important antioxidants, such as radicals of vitamins E and C back to their active non-radical forms (Jones 2002) (Fig. 9).”

What the sources say

• Not checked yetcites Jones 2002 source

In the paper

“For example, the Mn-salen complex (EUK-8) exhibits both SOD and catalase mimetic properties and has been found to ameliorate sepsis- or lipopolysaccharide-induced pulmonary dysfunction (Gonzales et al. 1995).”

What the sources say

• Not checked yetcites Gonzales et al. 1995

In the paper

“For example, the Mn-salen complex (EUK-8) exhibits both SOD and catalase mimetic properties and has been found to ameliorate sepsis- or lipopolysaccharide-induced pulmonary dysfunction (Gonzales et al. 1995).”

What the sources say

• Not checked yetcites Gonzales et al. 1995

In the paper

“Low molecular weight antioxidants represent an important line of cellular defense mechanisms against oxidants (Pinchuk et al. 2021).”

What the sources say

• Not checked yetcites Pinchuk et al. 2021 source

In the paper

“An effect of one electron oxidation by oxidants may result in the modification of protein-SH groups and consequently the formation of thiyl radicals (Protein-S·) and protein sulfenic acid (Protein-SOH) (Valko et al. 2006).”

What the sources say

• Not checked yetcites Valko et al. 2006 source

In the paper

“Since the standard one-electron reduction potential of (α-TO·/α-TOH) couple is about 500 mV and (Asc·−/AscH−) couple is 280 mV, vitamin C can regenerate vitamin E (α-TOH) from its radical form (α-TO·) according to the reaction2021”

What the sources say

• Not checked yetcites [2021]

In the paper

“This hypothesis has been confirmed later by the Alpha-Tocopherol/Beta-Carotene (ATBC) trial in Finland organized by the National Cancer Institute NIH (ATBC Trial 1996).”

What the sources say

• Not checked yetcites ATBC Trial 1996

In the paper

“The GSH/GSSG ratio is a good marker of oxidative stress of an organism (Hwang et al. 1992).”

What the sources say

• Not checked yetcites Hwang et al. 1992 source

In the paper

“Observational studies revealed that both high and low intake of Se is associated with an increased risk of cardiovascular disease (Rayman 2012).”

What the sources say

• Not checked yetcites Rayman 2012 source

In the paper

“Under conditions of high partial pressure of oxygen, radicals of carotenoids, Car·, originating from the reaction of ROS with a carotenoid molecule by hydrogen abstraction may further react with dioxygen according to the reaction (Young and Lowe 2001; Shin et al. 2020)24”

What the sources say

• Not checked yetcites Young and Lowe 2001 source
• Not checked yetcites Shin et al. 2020 source

In the paper

“Due to the lack of conjugation, flavanones usually have lower antioxidant activity (Jomova et al. 2019).”

What the sources say

• Not checked yetcites Jomova et al. 2019 source

In the paper

“However, it has been reported that the aryloxyl radicals are sometimes unstable showing a prooxidant behavior (Bors et al. 1995).”

What the sources say

• Not checked yetcites Bors et al. 1995 source

In the paper

“Cochrane Reviews reported a 30% reduced risk of cancer within the group with a high intake of Se (Vinceti et al. 2018).”

What the sources say

• Not checked yetcites Vinceti et al. 2018 source

In the paper

“Recently obtained results indicate that mitochondria play an important role in the production, metabolism, and activity of melatonin (Tan et al. 2016; Tan and Reiter 2019).”

What the sources say

• Not checked yetcites Tan et al. 2016 source
• Not checked yetcites Tan and Reiter 2019 source

In the paper

“ERG is a very good cytoprotecting agent against various cellular insults (Borodina et al. 2020).”

What the sources say

• Not checked yetcites Borodina et al. 2020 source

In the paper

“Antioxidant properties of flavonoids predominantly depend on the number and position of hydroxyl groups and their metal-chelating ability (Fig. 12) (Lomozova et al. 2022; Simunkova et al. 2021).”

What the sources say

• Not checked yetcites Lomozova et al. 2022 source
• Not checked yetcites Simunkova et al. 2021 source

In the paper

“The health-beneficial effects of flavonoids in the prevention of chronic diseases are predominantly related to their antioxidant properties manifested by the ability to terminate free radicals and effectively chelate redox metal ions.”

What the sources say

• Not checked yetcites Simunkova et al. 2019a, b

In the paper

“A positive correlation between ERG and its antidepressant properties has been reported (Nakamichi et al. 2016)”

What the sources say

• Not checked yetcites Nakamichi et al. 2016 source

In the paper

“The metal chelating activity of flavonoids results either (i) in the formation of metal-chelates which have lower catalytic efficiency in Fenton reaction than pure flavonoids (decreased number of metal binding sites is usually associated with lower catalytic activity) or (ii) metal flavonoid chelates can intercalate into DNA of cancer cells, triggering cell death (Simunkova et al. 2021).”

What the sources say

• Not checked yetcites Simunkova et al. 2021 source

In the paper

“Intake of ERG has been linked with longevity (Beelman et al. 2019).”

What the sources say

• Not checked yetcites Beelman et al. 2019 source

In the paper

“The metal chelating activity of flavonoids results either (i) in the formation of metal-chelates which have lower catalytic efficiency in Fenton reaction than pure flavonoids (decreased number of metal binding sites is usually associated with lower catalytic activity) or (ii) metal flavonoid chelates can intercalate into DNA of cancer cells, triggering cell death (Simunkova et al. 2021).”

What the sources say

• Not checked yetcites Simunkova et al. 2021 source

In the paper

“The antioxidant activity of flavonoids depends on the availability of the donation of phenolic hydrogens (Rice-Evans et al. 1996).”

What the sources say

• Not checked yetcites Rice-Evans et al. 1996 source

In the paper

“Car-OO· may behave as a prooxidant by further reaction with unsaturated lipids25”

What the sources say

• Not checked yetcites [25] source

In the paper

“However, over the years, large-scale clinical trials proved only limited health benefits of taking antioxidants (Halliwell 2022).”

What the sources say

• Not checked yetcites Halliwell 2022 source

In the paper

“In a 3 years randomized trial of the effect of vitamins E and C in atherogenic prevention has been shown that the subjects with a predisposition to atherosclerosis supplemented with vitamin E have increased plasma concentration of this vitamin (Salonen et al. 2000).”

What the sources say

• Not checked yetcites Salonen et al. 2000 source

In the paper

“Protein carbonyls have been found to be elevated in Alzheimer’s diseases, diabetes, renal diseases, and other disorders (Gil et al. 2006).”

What the sources say

• Not checked yetcites Gil et al. 2006 source

In the paper

“However, the double-edged sword of oxidative distress may involve a desirable mechanism of apoptosis, especially in cancer cells, either by natural causes or by anticancer drugs (Simunkova et al. 2019a, b).”

What the sources say

• Not checked yetcites Simunkova et al. 2019a, b

In the paper

“There are many examples of efficient antioxidants under in vitro conditions that undergo a switch from antioxidant to prooxidant behavior, or partly or completely lose their antioxidant properties under in vivo conditions (Simunkova et al. 2021).”

What the sources say

• Not checked yetcites Simunkova et al. 2021 source

In the paper

“Superoxide radical anion, generated from the enzyme xanthine oxidase (XO) plays an important role in the pathogenesis of ischemia-induced tissue injury (Vickenson and George 2020).”

What the sources say

• Not checked yetcites Vickenson and George 2020

In the paper

“Experiments using laboratory animals revealed that heart failure is also accompanied by increased superoxide radical formation by NOs in vessels leading to cardiomyopathy (Umar and Laarse 2010; Munzel et al. 2015).”

What the sources say

• Not checked yetcites Umar and Laarse 2010 source
• Not checked yetcites Munzel et al. 2015 source

In the paper

“Increased formation of ROS in mitochondria is a typical phenomenon in diabetic patients with cardiovascular diseases, typically with left ventricular hypertrophy and diastolic dysfunction (Jeong et al. 2016).”

What the sources say

• Not checked yetcites Jeong et al. 2016 source

In the paper

“Oxidized low-density lipoprotein is linked with the occurrence of atherosclerosis (Lara-Guzman et al. 2018).”

What the sources say

• Not checked yetcites Lara-Guzman et al. 2018 source

In the paper

“One of the most important is H2O2-activated Ca/calmodulin-dependent kinase II (CAMKII) responsible for excitation–contraction coupling.”

What the sources say

• Not checked yetcites Bennett and Lawan 2020 source

In the paper

“Various signs of increased oxidative stress have been reported in various cardiovascular-related diagnoses such as heart failure (Dai et al. 2012), ventricular hypertrophy (Dai et al. 2011), myocardial infarction (Merabet et al. 2012), diabetes (Anderson et al. 2009) and other conditions.”

What the sources say

• Not checked yetcites Dai et al. 2012 source
• Not checked yetcites Dai et al. 2011 source
• Not checked yetcites Merabet et al. 2012 source

In the paper

“With respect to antioxidant interventions, apart from vitamin E, other antioxidants such as carotenoids, ascorbic acid, and flavonoids have been shown to have a very mild effect on preventing oxidative damage (Halliwell 2020; Forman and Zhang 2021; Mangione et al. 2022).”

What the sources say

• Not checked yetcites Halliwell 2020 source
• Not checked yetcites Forman and Zhang 2021 source
• Not checked yetcites Mangione et al. 2022 source

In the paper

“Increased amounts of F2-IsoPs are detected in cardiovascular diseases and other clinical conditions (Milne et al. 2015).”

What the sources say

• Not checked yetcites Milne et al. 2015 source

In the paper

“The direct assessment of MDA and 4-HNE is not very sensitive, since the major portion of these reactive aldehydes is attached to proteins or other biomolecules and therefore before analysis, should be released, otherwise, they remain undetected (Esterbauer et al. 1991).”

What the sources say

• Not checked yetcites Esterbauer et al. 1991 source

In the paper

“It has been reported that the myocardial infarction increases NOX2-derived ROS that activated apoptotic pathways such as Apoptosis signal-regulating kinase 1-p38 pathway ((ASK-1)-p38MAPK) and Ca2+/calmodulin-dependent protein kinase II (CAMKII).”

What the sources say

• Not checked yetcites Erickson et al. 2008 source

In the paper

“In patients with very high BMI has been observed increased apoptosis in right atrial cardiomyocytes (Nieman et al. 2011).”

What the sources say

• Not checked yetcites Nieman et al. 2011

In the paper

“PRX4 has been proposed as a suitable biomarker of oxidative stress in diabetes (Abbasi et al. 2014).”

What the sources say

• Not checked yetcites Abbasi et al. 2014 source

In the paper

“A significant amount of ROS formed during mitochondrial dysfunction significantly contributes to the incidence of cardiovascular diseases (Bhatti et al. 2017).”

What the sources say

• Not checked yetcites Bhatti et al. 2017 source

In the paper

“Endothelial dysfunction precedes the development of atherosclerosis and hypertension, the main risk factors for myocardial infarction and heart failure (Scioli et al. 2020).”

What the sources say

• Not checked yetcites Scioli et al. 2020 source

In the paper

“The level of glutathionylated proteins reflects increased oxidative stress (Valko et al. 2006).”

What the sources say

• Not checked yetcites Valko et al. 2006 source

In the paper

“Transcription factor Nrf2 is activated in response to ROS-induced oxidative stress and triggers the expression of its target genes through binding to antioxidant response elements (Ma 2013).”

What the sources say

• Not checked yetcites Ma 2013

In the paper

“Severe oxidation of DNA is a precursor for the risk of some cancers, in particular, breast and lung cancers (Loft et al. 2013).”

What the sources say

• Not checked yetcites Loft et al. 2013 source

In the paper

“However, the problem is the poor reproducibility of quantitative methods, and therefore the application of oxLDL as a marker of oxidative stress in the prediction of cardiovascular diseases is doubtful.”

In the paper

“ROS are known to hyperactivate PI3K/Akt/mTOR (Phosphoinositide 3-Kinases/Protein kinase B/mammalian Target Of Rapamycin), an intracellular pathway playing an important role in cell cycle regulation, specifically proliferation, cancer, and longevity (King et al. 2015).”

What the sources say

• Not checked yetcites King et al. 2015 source

In the paper

“Vitamin C has anti-inflammatory properties by preventing adhesion and aggregation of leukocytes to the endothelium (Padayatty et al. 2003).”

What the sources say

• Not checked yetcites Padayatty et al. 2003

In the paper

“Recent results confirmed that Nrf2 has an inconsistent role in cancer.”

In the paper

“Hyperactivation of PI3K/Akt/mTOR oxidizes and inactivates the phosphatases PTEN and PTP1B (Salmeen et al. 2003).”

What the sources say

• Not checked yetcites Salmeen et al. 2003 source

In the paper

“Apoptosis mediated by inflammatory cytokines and oxidized low-density lipoproteins (LDL) can be attenuated by vitamin C (Rayment et al. 2003).”

What the sources say

• Not checked yetcites Rayment et al. 2003 source