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

In the paper

“It has been estimated that one puff of cigarette smoke contains approximately 1015 free radicals of various origins (Yang et al. 2008).”

What the sources say

• Not checked yetcites Yang et al. 2008 source

In the paper

“Approximately 4–5% of oxygen in the human body is converted to ROS by biological reductants.”

What the sources say

• Not checked yetcites Bandyopadhyay et al. 1999

In the paper

“A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents.”

In the paper

“Free radicals are chemical entities containing at least one unpaired electron in the outer shell which usually gives them high reactivity.”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 2015 source

In the paper

“ROS or RNS are formed during electron transfer reactions, by losing or accepting electron(s) (Halliwell and Gutteridge 2015).”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 2015 source

In the paper

“Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids.”

In the paper

“In contrast, excessive formation of ROS is responsible for disrupted redox homeostasis which in turn leads to oxidative stress and ROS-mediated damage to all important biomolecules including DNA, proteins, and membranes (Liguori et al. 2018).”

What the sources say

• Not checked yetcites Liguori et al. 2018 source

In the paper

“Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s and Parkinson’s diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging.”

In the paper

“Singlet oxygen is a very efficient oxidizing agent in biological systems and can cause damage to all biomolecules, including DNA.”

In the paper

“Ionizing radiation may cause radiolysis of water, accompanied by the formation of hydroxyl radicals (Nuszkiewicz et al. 2020).”

What the sources say

• Not checked yetcites Nuszkiewicz et al. 2020 source

In the paper

“The efficient formation of hydroxyl radicals is achieved when stoichiometric quantities of redox metals are present and when a reducing agent (O2·−) that can recycle metal ions back to their active reduced form is present (Valko et al. 2005)8”

What the sources say

• Not checked yetcites Valko et al. 2005 source

In the paper

“Under physiological conditions, a vast majority of superoxide radical is present in the form of the radical anion (O2·−), and approximately only 0.6% exists in the protonated form as hydroperoxyl radical HOO· (pKa = 4.8); O2·− is the conjugate base of a weak acid HOO· (de Grey 2002)1”

What the sources say

• Not checked yetcites de Grey 2002 source

In the paper

“Reactive nitrogen species (RNS) are nitrogen-containing species of which the most significant representative example is nitric oxide (NO·) (Ignarro et al. 1987).”

What the sources say

• Not checked yetcites Ignarro et al. 1987 source

In the paper

“Another very important source of ROS, including hydrogen peroxide and superoxide anion radicals are dynamic and metabolically active subcellular compartments, peroxisomes (Phaniendra et al. 2015).”

What the sources say

• Not checked yetcites Phaniendra et al. 2015 source

In the paper

“The above set of reactions, resulting in the formation of superoxide radicals, has been shown to be omnipresent and a critical component in biological systems (Poole 2015; Adams et al. 1969; Davies et al. 2022).”

What the sources say

• Not checked yetcites Poole 2015 source
• Not checked yetcites Adams et al. 1969 source
• Not checked yetcites Davies et al. 2022 source

In the paper

“In the course of this reaction, in neutral pH, metals (Fe or Cu) interact with carbonate and hydroperoxides resulting in the formation of carbonate radical anion CO3·−, which may dominate over the hydroxyl radicals when the concentration of bicarbonate is higher than 100 µM.”

What the sources say

• Not checked yetcites Illes et al. 2019 source

In the paper

“Hydroxyl radical is one of the most reactive radicals occurring in biological systems and causes damage to all important biomolecules involving DNA, proteins, and membranes (Valko et al. 2007).”

What the sources say

• Not checked yetcites Valko et al. 2007 source

In the paper

“Production of ATP is tightly linked with the formation of ROS which may be involved in the pathological states of an organism or physiological cell signaling (Valko et al. 2007).”

What the sources say

• Not checked yetcites Valko et al. 2007 source

In the paper

“The endoplasmic reticulum (ER) is a complex dynamic structure possessing many functions in the cell, the most important ones include calcium storage, lipid metabolism, and protein synthesis (Cao et al. 2022).”

What the sources say

• Not checked yetcites Cao et al. 2022 source

In the paper

“Hydrogen peroxide is a strong oxidant but the kinetics of its reaction with biomolecules is rather slow and therefore it can be accumulated in cells in relatively high concentrations (Andres et al. 2022).”

What the sources say

• Not checked yetcites Andres et al. 2022 source

In the paper

“Molecular oxygen in a triplet state contains two unpaired electrons with parallel spin states (↑↑) in antibonding π* orbitals and therefore is a biradical.”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 2015 source

In the paper

“Singlet oxygen has a short half-life, about 10–6 s, depending on the media (Valko et al. 2004).”

What the sources say

• Not checked yetcites Valko et al. 2004 source

In the paper

“GI problems involve Crohn’s disease, reflux, esophagus cancer, and other disorders (Bhattacharyya et al. 2014).”

What the sources say

• Not checked yetcites Bhattacharyya et al. 2014 source

In the paper

“There are three main forms of superoxide dismutase present in humans, Cu, Zn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) (Zelko et al. 2002).”

What the sources say

• Not checked yetcites Zelko et al. 2002 source

In the paper

“ERK plays important roles in the processes involving cell growth, cell proliferation, and cell survival (Lavoie et al. 2020).”

What the sources say

• Not checked yetcites Lavoie et al. 2020 source

In the paper

“Antioxidant enzymes represent an important defense mechanism against ROS-induced oxidative stress, causing damage to all cellular components (Mates et al. 1999).”

What the sources say

• Not checked yetcites Mates et al. 1999 source

In the paper

“Red meat contains high content of iron which may catalyze ROS formation in the colon in the process of digestion (Valko et al. 2001).”

What the sources say

• Not checked yetcites Valko et al. 2001 source

In the paper

“SOD was discovered in 1967 by Irwin Fridovich (McCord and Fridovich 1969).”

What the sources say

• Not checked yetcites McCord and Fridovich 1969 source

In the paper

“Four main MAPK cascades have been identified: ERK1/2 (extracellular signal-regulated kinases), c-Jun N-terminal kinases (JNK), p38 (p38 kinase), and the BMK1/ERK5 (big MAP kinase 1) (Schaeffer and Weber 1999).”

What the sources say

• Not checked yetcites Schaeffer and Weber 1999 source

In the paper

“SODs can be inhibited also by copper chelators such as EDTA and cuprizone (a copper‐specific chelator) (Zhu et al. 2014).”

What the sources say

• Not checked yetcites Zhu et al. 2014 source

In the paper

“Acrylamide can interact with hemoglobin and increase ROS formation (Bergmark et al. 1993).”

What the sources say

• Not checked yetcites Bergmark et al. 1993 source

In the paper

“P38 is a major pathway influencing cell proliferation, cell cycle, and apoptosis, and is activated in response to various environmental stresses, involving inflammatory cytokines, oxidative and nitrosative stress, and DNA damage (Shahab and Jamesdaniel 2022; Zhang et al. 2016).”

What the sources say

• Not checked yetcites Shahab and Jamesdaniel 2022 source
• Not checked yetcites Zhang et al. 2016 source

In the paper

“The family of NF-κB consists of five structurally similar members, involving p50/p105 (NF-κB1), p52/p100 (NF-κB2), RelA (p65), RelB, and c-Rel (Liu et al. 2017).”

What the sources say

• Not checked yetcites Liu et al. 2017

In the paper

“Cells under a higher partial pressure of oxygen are permanently exposed to attack by ROS which is balanced by the concerted action of a sophisticated antioxidant defense system (Bandyopadhyay et al. 1999).”

What the sources say

• Not checked yetcites Bandyopadhyay et al. 1999

In the paper

“A positive correlation between the high consumption of red meat and the incidence of colon cancer has been proposed (Valko et al. 2001).”

What the sources say

• Not checked yetcites Valko et al. 2001 source

In the paper

“A very large gradient (≈ 10,000) of calcium ions exists across the plasma membrane (Jomova et al. 2022).”

What the sources say

• Not checked yetcites Jomova et al. 2022 source

In the paper

“In addition, I-κB-Kinase (IKK) complex is the core component of NF-κB and is a target of ROS, affecting thus NF-κB and S-glutathionylation and inhibited IKKβ activity (Reynaert et al. 2006).”

What the sources say

• Not checked yetcites Reynaert et al. 2006 source

In the paper

“The key role of Ca2+ is ATP synthesis and mitochondrial ROS formation through oxidative phosphorylation and activation of enzymes (Lewis et al. 2014).”

What the sources say

• Not checked yetcites Lewis et al. 2014 source

In the paper

“The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) is an intracellular pathway involved in the regulation of a variety of critical cellular physiological processes involved in the cell cycle growth and proliferation and apoptosis, protein synthesis, and drug resistance in response to stimulation by growth factors, cytokines and hormones (Leslie and Downes 2002).”

What the sources say

• Not checked yetcites Leslie and Downes 2002 source

In the paper

“This enzyme catalyzes the dismutation of superoxide anion radical very effectively by a “Ping Pong” mechanism with remarkably high reaction rates according to the reaction (Zelko et al. 2002)12”

What the sources say

• Not checked yetcites Zelko et al. 2002 source

In the paper

“The nuclear factor-κB (NF-κB) is an important inducible transcription factor playing a key role in processes of the immune and inflammatory responses, cellular adhesion, differentiation, proliferation, and apoptosis (Bonizzi and Karin 2004).”

What the sources say

• Not checked yetcites Bonizzi and Karin 2004 source

In the paper

“The reaction proceeds in two steps; the first step involves the reduction of the first molecule of H2O2 accompanied by the formation of oxyferryl species (FeIVO) and in the course of the second step, the FeIVO complex is reduced by the second molecule of H2O2 to O2, and H2O molecules and free enzyme (Lardinois 1995; Nandi et al. 2019)14and15”

What the sources say

• Not checked yetcites Lardinois 1995 source
• Not checked yetcites Nandi et al. 2019 source

In the paper

“The abundance of GSH is unusually high, the cytosol concentration is ca 1–11 mM, mitochondria contain 6–10 mM, and nuclei 3–15 mM of GSH.”

What the sources say

• Not checked yetcites Lushchak 2012 source
• Not checked yetcites Valko et al. 2006 source

In the paper

“Vitamin C (ascorbic acid) is a water-soluble antioxidant present in the diet, supplements, and preservatives (Kazmierczak-Baranska et al. 2020).”

What the sources say

• Not checked yetcites Kazmierczak-Baranska et al. 2020 source

In the paper

“Manganese is a transition metal capable of oscillating between several oxidation states which makes it suitable for the accommodation of superoxide radical anion and the design of SOD mimetic compounds (Vincent et al. 2021).”

What the sources say

• Not checked yetcites Vincent et al. 2021 source

In the paper

“Prooxidant properties of vitamin C in the presence of redox-active metal ions and oxygen have been confirmed predominantly under in vitro conditions, occurrence under in vivo conditions has not been convincingly documented (Halliwell 1996).”

What the sources say

• Not checked yetcites Halliwell 1996 source

In the paper

“The most representative examples of small molecular antioxidants involve vitamins C, E, and A, polyphenols of which about half are flavonoids, carotenoids, glutathione, curcumin, melatonin, and others (Niki 2016).”

What the sources say

• Not checked yetcites Niki 2016 source

In the paper

“Catalase breaks down two molecules of hydrogen peroxide into two water molecules and one molecule of oxygen (Nandi et al. 2019)13”

What the sources say

• Not checked yetcites Nandi et al. 2019 source

In the paper

“GPx-1 acts in the intracellular environment and maintains the physiological level of hydrogen peroxide, which is important in mitochondrial function, thiol redox homeostasis, and signal transduction (Brigelius-Flohé and Maiorino 2013).”

What the sources say

• Not checked yetcites Brigelius-Flohé and Maiorino 2013 source

In the paper

“Compounds containing sulfur are usually good antioxidants able to accommodate unpaired electron(s), which in turn result in the formation of thiyl radicals (GS·), whose lifetime is rather high and therefore damage to biological molecules is very mild (Karoui et al. 1996)22”

What the sources say

• Not checked yetcites Karoui et al. 1996 source

In the paper

“This compound and its modified analog BXT-51072 were able to delay neurological deficits, and acute ischemic stroke, inhibit the inflammatory response, suppress oxidative damage, and other beneficial oxidative stress-reducing properties (Forman and Zhang 2021).”

What the sources say

• Not checked yetcites Forman and Zhang 2021 source

In the paper

“GPx reduces lipid hydroperoxides to alcohols and hydrogen peroxide to water (Lubos et al. 2011).”

What the sources say

• Not checked yetcites Lubos et al. 2011 source

In the paper

“Deficiency of Vitamin E is related to neurological problems (National Institutes of Health 2021).”

What the sources say

• Not checked yetcites National Institutes of Health 2021

In the paper

“These involve among others, the Se-based organic compound ebselen, possessing a wide substrate specificity (Sies 1993a).”

What the sources say

• Not checked yetcites Sies 1993a

In the paper

“A linear correlation between the reduction potentials of flavonoids and their antioxidant potential has been reported (Lindgerg Madsen et al. 2000).”

What the sources say

• Not checked yetcites Lindgerg Madsen et al. 2000

In the paper

“ERG reacts fast with hydroxyl radicals, and its reaction with hydrogen peroxide and superoxide radical anion is somewhat slower (Fahey 2001).”

What the sources say

• Not checked yetcites Fahey 2001 source

In the paper

“A low incidence of cardiovascular diseases has been linked to the consumption of red wine containing a high concentration of resveratrol, a multipurpose molecule possessing various beneficial and health-protecting properties, involving antioxidant, and antitumor properties.”

What the sources say

• Not checked yetcites Catalgol et al. 2012 source

In the paper

“In addition, flavonoids can activate the synthesis of antioxidant enzymes and regenerate vitamins with higher electron reduction potential of the corresponding couples, such as vitamin E (Fig. 12) (Simunkova et al. 2019a, b).”

What the sources say

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

In the paper

“Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant (Nakamichi et al. 2016) and neuroprotective (Yang et al. 2012) activities in mice.”

What the sources say

• Not checked yetcites Nakamichi et al. 2016 source
• Not checked yetcites Yang et al. 2012 source

In the paper

“Melatonin is found in various tissues other than the pineal gland, involving the pancreas, liver, brain, lens, thyroid, and others (Mahmood 2019).”

What the sources say

• Not checked yetcites Mahmood 2019 source

In the paper

“Se is an essential component of many proteins, called selenoproteins (Zhang et al. 2020).”

What the sources say

• Not checked yetcites Zhang et al. 2020 source

In the paper

“Melatonin acts together with vitamin D as “light sensors” to meet the requirements for light and dark (Minich et al. 2022).”

What the sources say

• Not checked yetcites Minich et al. 2022 source

In the paper

“ERG occurs in two tautomeric thione and thiol forms, the thione form being more abundant at physiological pH (Borodina et al. 2020).”

What the sources say

• Not checked yetcites Borodina et al. 2020 source

In the paper

“Resveratrol has been associated with the so-called “French paradox”, which has been reported in 1992, based on epidemiological data from the French population known for the low incidence of cardiovascular diseases despite the consumption of a high-fat diet (Catalgol et al. 2012).”

What the sources say

• Not checked yetcites Catalgol et al. 2012 source

In the paper

“ERG ameliorates oxidative stress at the sites of injuries and has been classified as an “adaptive antioxidant” because it does not interfere with the physiological function of ROS (Halliwell et al. 2016).”

What the sources say

• Not checked yetcites Halliwell et al. 2016 source

In the paper

“Supplements containing Se help to boost the immune system, Se is sometimes combined with vitamins C and E (Shakoor et al. 2021).”

What the sources say

• Not checked yetcites Shakoor et al. 2021 source

In the paper

“ERG has been found to be an effective antioxidant in cardiovascular diseases (Servillo et al. 2017), chronic pulmonary diseases (Rahman 2012), lung inflammatory diseases (Repine and Elkins 2012), and other pathologies.”

What the sources say

• Not checked yetcites Servillo et al. 2017 source
• Not checked yetcites Rahman 2012 source
• Not checked yetcites Repine and Elkins 2012 source

In the paper

“Ergothioneine (ERG) is a sulfur-histidine betaine amino acid possessing antioxidant properties (Fig. 14) (Borodina et al. 2020).”

What the sources say

• Not checked yetcites Borodina et al. 2020 source

In the paper

“Thus carotenoids behave under normal conditions as antioxidants, however, under a high partial pressure of oxygen (and high concentration) they may lose their antioxidant properties and behave as prooxidants.”

In the paper

“Since the thyroid gland contains a high amount of selenium, it has been expected that supplementation by Se may help to improve thyroid function. However, the results were not straightforward (Winther et al. 2015).”

What the sources say

• Not checked yetcites Winther et al. 2015 source

In the paper

“The concept of oxidative stress in greater detail has been for the first time defined by Prof. Sies in 1985 (Sies 1985, 2018, 2020a).”

What the sources say

• Not checked yetcites Sies 1985
• Not checked yetcites Sies 2018 source
• Not checked yetcites Sies 2020a

In the paper

“Myeloperoxidase (MPO) is a heme-containing peroxidase released mainly by neutrophils (Davies and Hawkins 2020).”

What the sources say

• Not checked yetcites Davies and Hawkins 2020 source

In the paper

“In view of this, a more complex definition of oxidative stress, based on the disruption of redox signaling has been proposed (Jones 2006).”

What the sources say

• Not checked yetcites Jones 2006 source

In the paper

“Xanthine oxidase catalyzes the oxidation of xanthine to uric acid (antioxidant) accompanied by the formation of superoxide radical anion, O2·−, and hydrogen peroxide (McCord 1985).”

What the sources say

• Not checked yetcites McCord 1985 source

In the paper

“There are many assays, which can be applied in the “quantification” of oxidative stress, however, whether oxidative stress is a consequence or cause of the diseases is impossible to conclude.”

In the paper

“Contrary to expectations, additional supplementation with vitamin C did not increase the level of vitamin E, which documents, that the in vitro redox recycling of vitamin E by vitamin C does not work in humans.”

What the sources say

• Not checked yetcites Salonen et al. 2000 source

In the paper

“Since the enhanced antioxidant status has not been shown to be effective in the alleviation of oxidative stress, a new approach based on the thiol redox pool has been proposed (Jones 2006).”

What the sources say

• Not checked yetcites Jones 2006 source

In the paper

“These products are structurally stable and suitable for chemical detection (Stadtman 2004).”

What the sources say

• Not checked yetcites Stadtman 2004 source

In the paper

“Melatonin occurs in mitochondria in higher abundance compared to blood. This is due to the higher requirements for an antioxidant pool in mitochondria containing electron transport chain (Tan et al. 2015).”

What the sources say

• Not checked yetcites Tan et al. 2015 source

In the paper

“Many natural antioxidants taken from diet or from supplements have very limited bioavailability and their in vitro antioxidant activity and ability to regenerate themselves have not been confirmed in cells or tissues (Jomova et al. 2019).”

What the sources say

• Not checked yetcites Jomova et al. 2019 source

In the paper

“Many in vitro experiments under different experimental conditions confirmed the good antioxidant activity of melatonin, however, levels of melatonin in certain body organs might not be high enough to exhibit antioxidant properties (Sanchez-Barcelo et al. 2010).”

What the sources say

• Not checked yetcites Sanchez-Barcelo et al. 2010 source

In the paper

“Cu, Zn-SOD is known to be increased as a response to certain therapies or in some diseases therefore determination of activities of different SODs is necessary (Crapo et al. 1992).”

What the sources say

• Not checked yetcites Crapo et al. 1992 source

In the paper

“Further studies documented the oxidation of vitamin E after the attack of ROS, however, the oxidation of vitamin E has not provided protection against lipids or damage to other biomolecules associated with chronic diseases (Niki and Noguchi 2021).”

What the sources say

• Not checked yetcites Niki and Noguchi 2021 source

In the paper

“XDH can be converted to XO by the oxidation of thiols (Fig. 19) (Enroth et al. 2000).”

What the sources say

• Not checked yetcites Enroth et al. 2000 source

In the paper

“The term oxidative stress in relation to biological systems appeared for the first time in the scientific literature in the early 70’s (Azzi 2022).”

What the sources say

• Not checked yetcites Azzi 2022 source

In the paper

“Various disease states are characterized by disturbed metal homeostasis, such as hemochromatosis (iron overload) and flavonoids in the presence of iron (or other redox metals) behave as prooxidants, increasing the total amount of ROS (Valko et al. 2005).”

What the sources say

• Not checked yetcites Valko et al. 2005 source

In the paper

“Thus, XO is one of the most important ROS-generating enzymes and can be used as a sensitive biomarker of oxidative stress.”

In the paper

“While EGCG is a good antioxidant in various radical scavenging assays, in plasma is its antioxidant activity limited (Rasaei et al. 2021).”

What the sources say

• Not checked yetcites Rasaei et al. 2021 source

In the paper

“Interestingly, in 2020–2021, during the COVID-19 pandemic period, melatonin was the most sought-after supplement to optimize levels of cytokines linked with disturbed sleeping (Minich et al. 2022).”

What the sources say

• Not checked yetcites Minich et al. 2022 source

In the paper

“Thus, the catalase activity in the studied system is conversely proportional to the obtained signal (Hadwan 2018).”

What the sources say

• Not checked yetcites Hadwan 2018 source

In the paper

“Melatonin and vitamin D act synergistically in skin protection (Wacker and Holick 2013).”

What the sources say

• Not checked yetcites Wacker and Holick 2013 source

In the paper

“MPO converts hydrogen peroxide and chloride anions to hypochlorous acid and protects the organism against toxins and pathogens.”

What the sources say

• Not checked yetcites Davies and Hawkins 2020 source

In the paper

“Oxidative eustress means “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 (Forman et al. 2010).”

What the sources say

• Not checked yetcites Forman et al. 2010 source

In the paper

“The presented results indicate, that in man, supplementation with high doses of antioxidants does not always ameliorate the oxidative stress component of various disease states of an organism or oxidative stress is not the only cause of the diseases.”

In the paper

“Heterogenous molecules originating from the nonenzymatic reaction of glucose or other saccharides with proteins or lipids are termed advanced glycation end products (AGEs) (Perrone et al. 2020).”

What the sources say

• Not checked yetcites Perrone et al. 2020 source

In the paper

“MPO-derived oxidant 3-Cl-Tyr is occurring in high-density lipoprotein (HDL) and therefore is a good biomarker of cardiovascular diseases (Bergt et al. 2004)”

What the sources say

• Not checked yetcites Bergt et al. 2004 source

In the paper

“Protein carbonyls, [C=O], (aldehydes or ketones) are protein modifications, formed on side chains of proteins following the oxidation of proline, arginine, lysine, and threonine.”

What the sources say

• Not checked yetcites Stadtman 2004 source

In the paper

“The concept of “total antioxidant capacity” has serious limitations and cannot be simply transferred to in vivo conditions (Sies 2007).”

What the sources say

• Not checked yetcites Sies 2007 source

In the paper

“Melatonin interferes with inflammatory processes by interacting with cyclooxygenase (COX2), which is a key mediator of inflammatory processes and promotes apoptosis in malignant cells (Favero et al. 2017; Chitimus et al. 2020).”

What the sources say

• Not checked yetcites Favero et al. 2017 source
• Not checked yetcites Chitimus et al. 2020 source

In the paper

“To date, more than 100 DNA adducts with ROS have been detected and the methods of their quantification have been well established (Dizdaroglu et al. 2002).”

What the sources say

• Not checked yetcites Dizdaroglu et al. 2002 source

In the paper

“Increased oxidative stress causes modifications of all subcellular organelles, including oxidation of endoplasmic reticulum Ca2+-ATPase and contractile proteins (actin and myosin being the most important) resulting in contractile dysfunction (Steinberg 2013).”

What the sources say

• Not checked yetcites Steinberg 2013 source

In the paper

“About 20 various AGEs have been detected in blood and tissues, as well as in foods.”

What the sources say

• Not checked yetcites Singh et al. 2001 source

In the paper

“Oxidative stress has been related to many pathological states of an organism (Halliwell and Gutteridge 2015).”

What the sources say

• Not checked yetcites Halliwell and Gutteridge 2015 source

In the paper

“Both peroxyl radicals and alkoxyl radicals are further cyclized and dependent on the type of polyunsaturated fatty acid, degraded into reactive aldehydes such as 4-hydroxynonenal (4-HNE) or malondialdehyde (MDA) (Fig. 21) (Ramana et al. 2014).”

What the sources say

• Not checked yetcites Ramana et al. 2014 source

In the paper

“In addition, JNKs (c-Jun N-terminal kinase) play an important role in insulin resistance, and p38 MAPK (p38 mitogen-activated protein kinase) has been shown to stimulate the uptake of glucose (Bennett and Lawan 2020).”

What the sources say

• Not checked yetcites Bennett and Lawan 2020 source

In the paper

“In the cells, the GSH/GSS ratio is greater than 30, and in the serum is about 10 times lower (Hwang et al. 1992).”

What the sources say

• Not checked yetcites Hwang et al. 1992 source

In the paper

“Lipid hydroperoxides react fast with Fe2+ to form alkoxyl radicals (LO·), and reaction with Fe3+ results in the formation of lipid peroxyl radicals (LOO·), however, the latter reaction is slower (Valko et al. 2006).”

What the sources say

• Not checked yetcites Valko et al. 2006 source

In the paper

“PRX2 has been found to be secreted by inflammatory cells and is elevated in synovial fluids and serum in patients with rheumatoid arthritis (Szabo-Taylor et al. 2012).”

What the sources say

• Not checked yetcites Szabo-Taylor et al. 2012 source

In the paper

“It has been proposed that glutathionylated hemoglobin detected in erythrocytes by Mass spectrometry (MS) is a good marker of oxidative stress under various conditions, such as renal diseases, diabetes, or hyperlipidemia (Ghezzi 2013).”

What the sources say

• Not checked yetcites Ghezzi 2013 source

In the paper

“Uncoupling of NOs results in a switch from nitric oxide to superoxide radical and peroxynitrite and suppressed bioavailability of nitric oxide and vasoconstriction (Santillo et al. 2015).”

What the sources say

• Not checked yetcites Santillo et al. 2015 source

In the paper

“In addition, stimulated AngII produces ROS which in turn causes mitochondrial dysfunction, mitochondrial DNA lesions, heart failure, fibrosis, and cardiac hypertrophy (Dai et al. 2016).”

What the sources say

• Not checked yetcites Dai et al. 2016 source

In the paper

“Cardiovascular diseases (CVD) have multifactorial origins and according to WHO are the major cause of death worldwide (Benjamin et al. 2017).”

What the sources say

• Not checked yetcites Benjamin et al. 2017 source

In the paper

“Vascular NOXs are regulated by a peptide-hormone, Angiotensin II (AngII) that stimulates the formation of NOX-dependent ROS which in turn activate Angiotensin II receptor type 1 (AT1) with a self-strengthening effect (Santillo et al. 2015).”

What the sources say

• Not checked yetcites Santillo et al. 2015 source

In the paper

“It has been proposed that the secretion of TRX is a response to increased oxidative stress which can be inhibited by the antioxidants (Kondo et al. 2004).”

What the sources say

• Not checked yetcites Kondo et al. 2004 source

In the paper

“Isoprostanes are specific prostaglandin-like molecules formed by the non-enzymatic ROS-mediated peroxidation of PUFAs, involving for example arachidonic acid (Milne et al. 2015).”

What the sources say

• Not checked yetcites Milne et al. 2015 source

In the paper

“The most abundant non-fluorescence AGEs involve carboxymethyl-lysine (CML), and carboxyethyl-lysine (CEL). Fluorescence AGEs involve methylglyoxal-lysine and pentosidine (Singh et al. 2001).”

What the sources say

• Not checked yetcites Singh et al. 2001 source

In the paper

“Elevated levels of cysteinylated albumin detected by MS have been associated with kidney diseases and diabetes, and in addition, hepatic diseases (Nagumo et al. 2014).”

What the sources say

• Not checked yetcites Nagumo et al. 2014 source

In the paper

“NOX activity has been found to be increased in patients with metabolic syndrome and increased plasma levels of oxidized LDL and nitrotyrosine (Fortuno et al. 2006).”

What the sources say

• Not checked yetcites Fortuno et al. 2006 source

In the paper

“Vitamin C can reduce apoptosis in vascular smooth muscle cells and prevent the instability of plaques (Lehr et al. 1994).”

What the sources say

• Not checked yetcites Lehr et al. 1994 source

In the paper

“Vitamin D alone but more convincingly in combination with vitamin E decreased oxidative stress in cardiomyocytes, reduced inflammatory markers, and suppressed apoptosis, hypertrophy, and other ailments in obese rats (Farhangi et al. 2017).”

What the sources say

• Not checked yetcites Farhangi et al. 2017 source

In the paper

“Mice supplemented with resveratrol exhibit prolonged survival, less frequently occurring cardiac fibrosis, and improved diastolic function (Sung et al. 2015).”

What the sources say

• Not checked yetcites Sung et al. 2015 source

In the paper

“In a clinical trial, it has been reported that subjects drinking three cups of green tea for a period of four months have restored endothelial dysfunction and reduced 8-iso-prostoglandin-F2α, a useful oxidative stress marker.”

What the sources say

• Not checked yetcites Oyama et al. 2010 source

In the paper

“Intake of strawberries for 30 days can decrease levels of LDL cholesterol and triglycerides and provide partial protection against cardiovascular diseases (Alvarez-Suarez et al. 2014).”

What the sources say

• Not checked yetcites Alvarez-Suarez et al. 2014 source

In the paper

“CHAOS trial demonstrated that α-tocopherol is able to reduce the incidence of myocardial infarction, however, failed to reduce the mortality in cardiovascular diseases (Stephens et al. 1996).”

What the sources say

• Not checked yetcites Stephens et al. 1996 source

In the paper

“High levels of ROS have been shown to trigger cell cycle arrest and cancer cell death (Moon et al. 2010).”

What the sources say

• Not checked yetcites Moon et al. 2010 source

In the paper

“ROS can either (i) promote protumorigenic signaling supporting the proliferation and survival of cancer cells or (ii) conversely promote antitumorigenic signaling and oxidative stress-induced cancer cell death (Reczek and Chandel 2017).”

What the sources say

• Not checked yetcites Reczek and Chandel 2017 source

In the paper

“Vitamin C has the ability to prevent LDL oxidation and consequently slows down the peroxidation of lipids (Maeda et al. 2000).”

What the sources say

• Not checked yetcites Maeda et al. 2000 source

In the paper

“Thus, dysregulation of the PI3K/Akt pathway by excessive ROS production in various cancers is well established and is a critical target in anticancer therapy.”

In the paper

“Delphinidin, an anthocyanin, a primary plant pigment, containing 6 hydroxyl groups in its structure possesses ROS scavenging properties and is able to prevent apoptosis of endothelial cells under in vitro conditions via interference with NO-signaling pathways (Martin et al. 2003).”

What the sources say

• Not checked yetcites Martin et al. 2003 source

In the paper

“CRP is a good marker of inflammation and has been found to be reduced by vitamin E (Patrick et al. 2001).”

What the sources say

• Not checked yetcites Patrick et al. 2001

In the paper

“Compare to healthy cells, cancer cells are characterized by increased formation of ROS and therefore to avoid ROS-induced cell death, cancer cells restore their ROS homeostasis by increasing their antioxidant capacity (Valko et al. 2006).”

What the sources say

• Not checked yetcites Valko et al. 2006 source

In the paper

“Oral administration of 2 g of vitamin C in healthy populations helped to reduce aggregation platelet and arterial stiffness, however, the exact mechanism has not been fully explored (Wilkinson et al. 1999).”

What the sources say

• Not checked yetcites Wilkinson et al. 1999 source

In the paper

“Activated mutations within this pathway represent the most frequent oncogenic factor for many cancers (Khotskaya et al. 2017).”

What the sources say

• Not checked yetcites Khotskaya et al. 2017 source

In the paper

“Vitamin E inhibits the protein kinase C pathway, NF-kappa B, and IkappaB degradation, all activated by oxidized low-density lipoprotein (LDL) (Goya et al. 2006).”

What the sources say

• Not checked yetcites Goya et al. 2006 source

In the paper

“Resveratrol has also been found to activate eNOS which may prevent hypertension in obese mice (Huang et al. 2018).”

What the sources say

• Not checked yetcites Huang et al. 2018 source

In the paper

“A diet enriched with fruits and vegetables or antioxidants in the form of supplements lowered the risk of incidence and mortality in patients suffering from cancer (Genkinger et al. 2004).”

What the sources say

• Not checked yetcites Genkinger et al. 2004 source

In the paper

“Vitamin E has been reported to decrease monocyte recruitment as a result of suppressed formation of foam cells and reduce expression of scavenger receptors (SRs) on macrophages (Zapolska-Downar et al. 2000).”

What the sources say

• Not checked yetcites Zapolska-Downar et al. 2000 source

In the paper

“Conversely, expressed mutant Parkin results in increased levels of carbonyls, peroxidation of lipids, and nitrated proteins (Hyun et al. 2002).”

What the sources say

• Not checked yetcites Hyun et al. 2002 source

In the paper

“Increased levels of iron have been confirmed in the PD midbrain, which in turn results in iron-induced oxidative stress and neurodegeneration (Chinta and Andresen 2008).”

What the sources say

• Not checked yetcites Chinta and Andresen 2008

In the paper

“In conclusion, although various antioxidants have been shown to be effective in ameliorating symptoms of AD, available data from pre-clinical studies are not very convincing to be applied in further studies.”

In the paper

“Knocked down PINK1 in SHSY5Y cells results in inhibition of mDNA synthesis, disruption of key indicators of mitochondrial activity, mitochondrial membrane potential, and suppressed production of ATP (Gegg et al. 2009).”

What the sources say

• Not checked yetcites Gegg et al. 2009 source

In the paper

“α-Synuclein has been reported to cause dysfunction of mitochondrial complex I in PD which in turn increases levels of ROS and consequently ROS-induced oxidative stress (Winklhofer and Haass 2010).”

What the sources say

• Not checked yetcites Winklhofer and Haass 2010 source

In the paper

“Aminochrome is a highly reactive molecule capable of forming adducts with α-synuclein and ROS such as superoxide radical anion and depleting NADPH (Norris et al. 2005).”

What the sources say

• Not checked yetcites Norris et al. 2005 source

In the paper

“This cell line with overexpressing wild-type and mutant Parkin exhibits decreased levels of ROS and resistance to apoptosis induced by 6-hydroxydopamine (Jiang et al. 2004).”

What the sources say

• Not checked yetcites Jiang et al. 2004 source

In the paper

“DJ-1 is expressed in neurons and glial cells and acts as a ROS scavenger and transcriptional co-activator and molecular chaperon (Yokota et al. 2003).”

What the sources say

• Not checked yetcites Yokota et al. 2003 source

In the paper

“DJ-1 exposed to oxidative stress undergoes oxidation of Cysteine106 and translocates from cytoplasm to mitochondria or to the nucleus (Junn et al. 2009).”

What the sources say

• Not checked yetcites Junn et al. 2009 source

In the paper

“The above-described biochemical disturbances result in dopamine oxidation to dopamine-quinones or 6-hydroxydopamine, both involved in neurodegeneration (Hastings 2009).”

What the sources say

• Not checked yetcites Hastings 2009 source

In the paper

“Increased levels of redox metals act catalytically and contribute to the formation of damaging ROS and the occurrence of oxidative stress in the brain via the Fenton reaction (Valko et al. 2005)”

What the sources say

• Not checked yetcites Valko et al. 2005 source

In the paper

“ROS levels directly influence synaptic efficiency, characterized as the most important origin of neuronal dysfunction in PD.”

In the paper

“Significantly decreased levels of CoQ10 have been detected in the cortex of post-mortem brain tissues of Parkinson’s brains. In addition, the level of the oxidized form of ubiquinone has been found to be increased compared to healthy subjects (Sohmiya et al. 2004).”

What the sources say

• Not checked yetcites Sohmiya et al. 2004 source

In the paper

“Alzheimer’s disease (AD) is a multifactorial disease characterized by the degeneration of the cells in the brain (Knopman et al. 2021).”

What the sources say

• Not checked yetcites Knopman et al. 2021 source

In the paper

“For example, nigral neurons are less abundant with the L-type Ca2+ channels and are characterized by low oscillations of Ca2+, more expressed calcium-binding proteins calbindins, and therefore exhibit lower susceptibility to damage in PD (Khaliq and Bean 2010).”

What the sources say

• Not checked yetcites Khaliq and Bean 2010 source

In the paper

“Its location close to the membranes protects them from free radicals-induced damage and prevents peroxidation of lipids and DNA damage (Crane 2001).”

What the sources say

• Not checked yetcites Crane 2001 source

In the paper

“It has been declared, that neurotoxic 6-hydroxydopamine (and also superoxide radical) is able to release “free iron” from ferritin which in turn may participate in Fenton chemistry, forming ROS and initiating lipid peroxidation (Monteiro and Winterbourn 1989).”

What the sources say

• Not checked yetcites Monteiro and Winterbourn 1989 source

In the paper

“PINK1 mutations disturb kinase functions and neuroprotection.”

In the paper

“GSH therapy improved the performance of patients, with nearly half a decline in disability of patients which lasted for about three months after interrupted therapy.”

What the sources say

• Not checked yetcites Sechi et al. 1996 source

In the paper

“Of 500 genes on chromosome 21, 18 genes influence gene expression, and more than 20 genes are involved in metabolic functioning (Sturgeon and Gardiner 2011).”

What the sources say

• Not checked yetcites Sturgeon and Gardiner 2011 source

In the paper

“Although supplementation with antioxidants in patients with Down syndrome improves oxidative stress biomarkers and the overall antioxidant status of an organism. However, no improvements in cognitive performance or retardation of cognitive decline have been observed (Rueda Revilla et al. 2020).”

What the sources say

• Not checked yetcites Rueda Revilla et al. 2020 source