Open access peer-reviewed chapter

Thiols: Role in Oxidative Stress-Related Disorders

Written By

Abdulsamed Kükürt, Volkan Gelen, Ömer Faruk Başer, Haci Ahmet Deveci and Mahmut Karapehlivan

Submitted: 17 January 2021 Reviewed: 17 February 2021 Published: 20 March 2021

DOI: 10.5772/intechopen.96682

From the Edited Volume

Accenting Lipid Peroxidation

Edited by Pınar Atukeren

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Abstract

The effects of oxidative stress occur as a result of peroxidative damage of the macromolecule and membranes of the cells and with the disruption of metabolic activities in the components of the cells in living organisms. Organ and tissue pathologies are known to occur when oxidative stress is excessive in the body. It is known that thiols are one of the main protective mechanisms of the body against oxidative stress. Thiols have been shown to play important roles in enzymatic reactions, apoptosis, detoxification and antioxidant protection in the body. Many studies have shown changes in thiol status and thiol/disulphide homeostasis in various diseases such as digestive system, respiratory system, reproductive system, urinary system, metabolic diseases and cancer. This also shows that the thiol state is very important in the pathogenesis of oxidative stress-mediated diseases. Therefore, it is thought that interventions that can improve thiol status may contribute to the prevention or treatment of oxidative stress-related diseases.

Keywords

  • antioxidant
  • glutathione
  • oxidative stress
  • oxidative stress-mediated disorders
  • taurine
  • thiol-disulphide homeostasis
  • thioredoxin

1. Introduction

Oxygen is a potentially toxic molecule, although the aerobic organisms must survive. During biochemical reactions vital to living organisms, oxygen reduced, resulting in intermediate metabolic products known as reactive oxygen species (ROS), which cause oxidative damage to many tissues. ROS is called “oxidant” or “free radical” due to the oxidative destruction they create and form in all living organisms that metabolize molecular oxygen [1]. Free radicals are very short-lived reagents, separating other electrons around high-energy electrons and disrupting their structure. Therefore, free radicals are dangerous to the organism [2, 3].

There are many defense mechanisms in the organism to prevent ROS formation and the damage caused by them. These mechanisms are generally called “antioxidant defence systems” or “antioxidants” for shortly [4]. Antioxidants serve in the body by controlling the metabolization and levels of free radicals formed as a result of normal metabolism or pathological conditions and preventing or repairing the damage that may occur by these radicals [5, 6]. In the living organism, there is a balance between the rate of formation and elimination of free radicals. This balance is called the “oxidative balance” that prevents the body from being affected by free radicals. If the oxidative balance is disturbed in favor of free radicals, oxidative stress occurs, which is one of the factors that ultimately causes damage to cells and tissues [7, 8].

All biomolecules are subject to free radical attack. But among them, lipids are the most easily affected [9]. The membranes and cell organelles that surround the cells contain a large amount of unsaturated fatty acids (PUFA). Due to the high affinity of the oxygen molecule to PUFA in the cell membrane, there is a close relationship between the two. Oxygen binds to double ligaments in PUFA found in tissues, causing lipid peroxidation [10, 11]. Lipid peroxidation is a harmful chain reaction. It can directly damage the membrane structure or damages by producing reactive aldehydes. These compounds are either metabolized at the cell or diffuse damage from initial domains to other parts. Thus, the structure of lipids in the cell membrane is disturbed, permeability for ions increases and cell death occurs [12].

Reactive nitrogen species (RNS) are another reactive species group that is as important as ROS. Nitric oxide (NO), a free radical, is the most substantial member of this group. It has the ability to directly or indirectly affect cells and tissues. As it can directly affect itself, while indirect are mediated RNS produced the interaction of NO with superoxide radicals (O2−•) or oxygen (O2). Most of its direct physiological effects are cyclic guanosine 3′,5’monophosphate-mediated (cGMP). It can also interact with proteins containing iron and zinc or create S-nitrosothiols through nitrosylation [2, 13, 14, 15, 16, 17]. Many antioxidants work in the organism to prevent damage caused by ROS and RNS. Antioxidants, present in considerably lower concentrations than the substrate, are substances that can protect an oxidation-sensitive substrate from peroxidative damage. Biological antioxidants contain all compounds that protect cellular lipids, proteins and nucleic acids from peroxidative damage. One of these compounds is thiols. Thiols play a crucial biologic role among these compounds due to their capacity to react with free radicals and their strong reducing capabilities [18].

Thiols are a member of the class of organic compounds containing sulfhydryl group (-SH). They consist of a hydrogen atom and a sulfur atom attached to a carbon atom [19]. In the organism, in the oxidation created by ROS, excess electrons pass to thiols and disulphide bonds are formed. Due to the oxidative balance, electrons in these reversible bonds can return to thiols. The antioxidant ability of thiol-disulphide homeostasis is important in enzymatic reactions, signal transduction, detoxification, transcription, regulation of enzymatic activation, cellular signaling mechanisms and apoptosis reaction [20, 21, 22]. With these in mind, in this chapter, reactive oxygen species, nitric oxide, lipid peroxidation, oxidative stress and the role of thiols in antioxidant defense is summarized and has been explained how thiol status changes in conditions associated with oxidative stress.

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2. Biochemistry of reactive oxygen and nitrogen species

Free radicals and non-radical intermediates are commonly referred to as ROS. Species that contain unpaired electrons are free radicals. Species with unpaired electrons in their structure are free radicals, and because of this unpaired electron shell, free radicals have high reactivity. The most important sources of free radicals in biological systems are oxygen and nitrogen [23]. In the electron transfer chain, cells constantly convert small amounts of O2 to ROS. ROS can be produced in many ways in the organism, including the respiratory burst that occurs in active phagocytes [24]. Respiratory burst, also known as “oxidative burst”, is the event of a rapid release of ROS such as O2−• and hydrogen peroxide (H2O2) from different cell types. Generally, these chemicals are produced by immune system cells such as neutrophils and macrophages as a result of infection of the organism by bacteria and fungi [25, 26]. In phagocytes, the respiratory burst that occurs to break down bacteria plays an important role in the immune system. O2−• is produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a family of enzymes commonly found in many cells. In neutrophils and monocytes, myeloperoxidase is involved in combining H2O2 with CI-to produce hypochlorite, which plays a role in destroying bacteria [25].

Reactive oxygen species formation, as natural result of aerobic metabolism, has an important role in maintaining tissue oxygen homeostasis. O2−•, H2O2 and hydroxyl (OH) radicals are produced in mitochondria as normal metabolic by-products. Other important intracellular sources of ROS are peroxisomal enzymes, flavoprotein oxidases and microsomal cytochrome P450 enzymes [27]. ROS also play an important role in various physiological processes such as the functioning of normal vascular cells and maintenance of vessel diameter regulation [28]. It is stated that in biological systems, ROS participate in differentiation, proliferation, growth, apoptosis, cytoskeleton, migration and contraction regulation and play a role in the control of inflammatory response by stimulation of growth factor [29, 30].

Mitochondria are the main source of the O2−• anion most commonly found under physiological conditions [31]. The O2−• anion is formed by adding an electron to dioxygen. However, it is unstable because it can react spontaneously in aqueous solutions and convert into H2O2 and O2 [32]. In the respiratory chain, in particular, the O2−• anion is formed by the leakage of electrons from complex I and III into O2. The rate of formation depends on the number of electrons and increases with hyperoxia and high glucose concentration. The decrease in oxygen availability, acting as the final electron acceptor for complex IV, causes the accumulation of electrons. Because the O2−• anion is charged, it cannot pass through the membrane and remains in the mitochondrial matrix [23]. O2−• anion can convert to O2 by reducing Fe3+ ion to Fe2+. O2−• is detoxified with superoxide dismutase (SOD) enzymes and converted into H2O2 [32, 33].

Hydrogen peroxide is not a free radical, but it is mentioned in ROS because it is closely related to the detoxification or generation of free radicals [32]. It is not polar, so it can easily pass through the membranes of cells and organelles and therefore acts as a secondary messenger in a wide range of signal transduction pathways. It is detoxified into the water by catalase (CAT) and glutathione peroxidase (GPx). Imbalances in O2−• and H2O2 levels can result in the formation of OH radicals, which are far more dangerous than them [4]. The main source of the OH radical is metal-catalyzed Haber-weiss reaction [34] and the second source is the Fenton-type reaction [35]. It has been reported that the OH radical can react with any biological molecule in its immediate vicinity and there is no known scavenger because it is very reactive [23].

2.1 Nitric oxide

Nitric oxide is produced during the reaction which arginine is converted to citrulline catalyzed by nitric oxide synthase (NOS) which is NADPH-dependent enzyme [36, 37]. There are three isoforms of NOS: neuronal (nNOS) endothelial (eNOS) and inducible (iNOS) and it is known to be present in every cell component [17, 38]. NO is an uncharged lipophilic molecule containing unpaired electron. Although NO is not a highly reactive radical, it is important in that it can form other reactive intermediates that have an impact on protein function and the function of all organisms, as well as trigger nitrosative damage in biomolecules [39]. Therefore; it can function as an antioxidant or as an oxidant. NO, blood pressure regulator and a neurotransmitter, can produce powerful oxidants during pathological conditions [28].

The interaction of excessive amounts of O2−• anion with NO leads to the formation of the peroxynitrite anion (ONOO). ONOO, a cytotoxic radical, causes tissue damage and oxidizes low-density lipoproteins (LDL) [4, 40, 41]. It can also directly cause protein oxidation and DNA oxidation. ONOO can form prooxidant nitrogen dioxide (NO2) and OH by self-decomposition [42]. It is suggested that NO can increase the production of reactive oxygen and nitrogen species and inhibit cytochrome C oxidase in mitochondria, which can alter the activity of various processes such as respiration, mitochondrial biogenesis and oxidative stress [37]. It plays a critical role in inflammation-related carcinogenesis by activating the redox-sensitive transcription factor with nitrosative stress caused by NO, which has an important regulatory role for cellular functions. It is stated that by increasing the level of NO in plasma, it can reduce the concentration of uric acid and ascorbic acid and cause lipid peroxidation [28].

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3. Lipid peroxidation

Reactive oxygen species, produced in mitochondria and extramitochondrial regions, react with polyunsaturated fatty acids (PUFA) found in complex lipids and lipoproteins, such as phospholipids found in cellular membranes, which are highly sensitive to oxidative changes. The process that causes degradation of PUFAs by chemically modified by ROS is called lipid peroxidation [43].

Lipid peroxidation in membranes is initiated by the contribution of ROS or separation of the hydrogen atom by ROS from the methylene group located between two double bonds in the PUFA. Conjugated dienes made up of PUFA react with oxygen present in the membranes at a very high rate and form a peroxyl radical (ROO). Since ROO radicals are particularly highly reactive to neighboring PUFA chains, they spread the lipid peroxidation process by removing hydrogen from them. In this reaction, carbon centred radicals and lipid hydroperoxide are formed. Lipid peroxides can react with transition metal ions (iron, copper ions) to form alkoxyl radicals (RO) [4, 44]. Metal ions can cause the lipid peroxide molecule to become unstable, leading to its degradation into smaller products. These products range from simple hydrocarbons to various ketones and aldehydes. The decomposition products of lipid peroxides are aldehydes such as malondialdehyde (MDA), acrolein, 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) [43, 45]. Commonly used lipid peroxidation markers are MDA and HNE. HNE is formed as a peroxidation product of omega-6 unsaturated fatty acids, while MDA is essentially a PUFA peroxidation product with more than two double bonds such as arachidonic acid [4].

Biomolecules undergo a lipoxidation reaction by lipid peroxidation end products such as MDA, 4-HNE and acrolein. Irreversible nonenzymatic modifications occur when these products react with lysyl (ε-NH2), histidyl (imidazole) and cysteinyl (-SH) groups in the polypeptide chain. MDA-lysine and HNE-protein compounds formed by lipoxidation are called advanced lipoxidation end-products (ALE) [46, 47, 48].

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4. Antioxidant defense system

Antioxidants, when present in low concentrations, are generally defined as substances that significantly inhibit or delay oxidative processes while they oxidize themselves, in relation to oxidizable substrates [49]. They neutralize free radicals and oxidize themselves by accepting highly reactive unpaired electrons [4]. Various transcription factors in the human body are activated or inhibited depending on the relative oxidant/antioxidant ratio. Thus, many signal paths are controlled by redox balance. The endogenous defense system consists of antioxidant compounds and specific enzymes that catalyze their antioxidant activities. There are a wide variety of powerful antioxidants that cells use, such as vitamins (C, E, A) and enzymes (CAT, GPx, SOD and thioredoxin reductase). Other non-enzymatic antioxidants available to cells include GSH, α-lipoic acid, taurine and coenzyme Q10, carotenoids and polyphenols. Especially GSH and taurine, which are thiol antioxidants, are of great importance in maintaining the redox balance [50, 51, 52, 53].

4.1 Thiols and some of the important thiol antioxidants

Thiols are biological mercaptans (R-SH), while biological mercaptans are called biothiols. Biothiols can be classified as low molecular weight free thiols and large molecular weight protein thiols. Thiols found in biological systems play a role in the coordination of antioxidant defense systems [54]. It contains protein thiols in plasma, protein sulfhydryl groups and protein mix disulphides consisting of cysteine, cysteinylglycine, homocysteine and GSH. These thiols are also available in the form of low molecular mass disulphides, homocystine, cystinylglycine, cystine and GSSG [19]. While GSH/GSSG, especially in reduced form, consists of the low molecular weight sulfhydryl/disulphide pool inside the cell, cysteine/cystine in the form of disulphide in plasma and outside the cell as a whole [55]. It has been reported that dynamic thiol disulphide balance plays a crucial role in antioxidant system [20]. Total thiol (TT), especially protein thiol (-SH) groups in the body are considered as the main plasma antioxidants of the living organism. Most of these thiol (-SH) groups are found in albumin and constitute the major reducing groups found in body fluids [56].

Thiols play important physiological roles in processes requiring sulfur and are highly reactive, the -SH groups are readily oxidized or reduced in the presence of a catalyst [57, 58, 59]. Thiols can act as electron acceptors, reducing unstable free radicals by oxidizing, so they are powerful antioxidants. Despite their high reactivity, thiols’ antioxidant potential depends on environmental, structural and catalytic factors [60, 61, 62].

Cysteine can be synthesized endogenously from methionine. Methionine, an essential amino acid in the diet, is endogenously metabolized to homocysteine and then to cysteine; Its conversion is rate limited by a few enzymes [63]. As an amino acid, cysteine has important structural roles and can bind thiol side chains to metals such as zinc, copper and iron, which are crucial for enzymatic functions. The thiol side chain of cysteine also allows it to be included in the tri-peptide thiol antioxidant GSH. Besides, cysteine metabolism through the cysteine-sulfinic acid pathway can generate taurine, although enzymatically the rate is limited, this pathway is much more complex than that of GSH [64, 65]. Both GSH and taurine are formed from cysteine with bioactive thiol groups. Although intermediate levels of cysteine are important for cellular signaling pathways, high plasma levels have been associated with cardiovascular and neurological diseases [66, 67, 68]. Additionally, high intracellular levels can increase oxidative DNA damage through the Fenton reaction [69].

4.1.1 Thioredoxin system

Thioredoxin (Trx) was first discovered in E.coli in 1964 [70]. Trx’s are proteins that act as regulators in redox reactions and are found in all eukaryotic and prokaryotic organisms [71]. The Cys-Gly-Pro-Cys division is located in its active region [72]. Cytosolic thioredoxin-1 (Trx1) and mitochondrial thioredoxin-2 (Trx2) are part of the thioredoxin system, an essential and important antioxidant system for the maintenance of intracellular redox state, and play an important role in cellular redox balance and normal cell and tumor cell signaling [73, 74]. Trx exerts its antioxidant effects primarily by acting as an electron donor for peroxiredoxins. Trx is a small molecular weight protein that functions as an antioxidant by facilitating the reduction of other proteins containing the thiol (-SH) group via cysteine thiol-disulphide (-S-S-) exchange, and ribonucleotide reductase, an essential enzyme in the replication of deoxyribonucleic acid (DNA) for a hydrogen donor [75].

Thioredoxin reductases (TrxR) is a member of the flavoprotein family of pyridine nucleotide-disulphide oxidoreductases such as glutathione reductase (GSR), lipoamide dehydrogenase, mercury ion reductases [75, 76]. Members of this family include the active site in each monomer comprising the FAD, NADPH binding site and redox-active disulphide. It has a selenocysteine residue in its active site [73]. The disulphides in the active part of the TrxR reduce the substrate by catalyzing the electron transfer from NADPH to FAD. TrxRs reduce the thioredoxin protein containing two different cysteine amino acids (Trx1; Cys32 and Cys35, Trx2; Cys31 and Cys34) in its catalytic region. TrxRs have been reported to be associated with lipoic acid, lipid hydroperoxidase, cytotoxic and antibacterial polypeptide NK-lysin, dehydroascorbic acid, vitamin K, ascorbyl free radical, tumor suppressor protein p53 as well as Trx protein [71, 76, 77, 78, 79, 80]. It has been stated that mammalian thioredoxin reductase has three different isoenzymes, cytosolic TrxR1, mitochondrial TrxR2 and TrxR3, which is specific to testicles containing glutaredoxin region in the N terminal region [81].

Thioredoxin system has various roles in organisms and reflects the importance of the -SH group together with disulphide (-S-S-) in many reactions that are crucial in cell regulation [82]. It was previously thought that Trx was mainly involved in protecting against oxidative stress, scavenging ROS through its interaction with peroxiredoxin and working to control cellular redox balance. As a result of the studies, it has been shown that Trx contributes to redox-dependent cellular processes such as signal transduction, gene expression, apoptosis and cell growth [83, 84]. The reduced Trx binds apoptosis signal kinase-1 (ASK-1) and stops apoptosis [85]. Trx is released in response to oxidative stress and extracellular Trx exerts cytoprotective effects in inflammatory and oxidative conditions [86].

4.1.2 Glutathione system

Glutathione (GSH = γ-glutamylcysteinylglycine) is abundant in the human body. It is a tripeptide synthesized from three amino acids (cysteine, glycine and glutamate). It is a low molecular weight intracellular thiol compound and is mostly synthesized in the liver and is found in all cell types. As the regulator of intracellular redox homeostasis, most of it is stored in reduced form in the nucleus, endoplasmic reticulum, and mitochondria. The thiol group (-SH) of glutathione reduces the number of free radicals by binding to the un-shared electrons of free radicals formed as a result of oxidative stress. There are two forms in the organism: reduced (GSH) and oxidized (GSSG). The thiol-containing cysteine molecule in GSH, which is predominantly in the cell, allows ROS to take part in antioxidant roles by taking part in both degradation and removal [87, 88, 89].

The glutathione system acts as a leading cellular defense mechanism against oxidants. GSH is not only a direct ROS scavenger but also an antioxidant that has an important act in the regulation of intracellular redox status. The system consists of GPx, GSR and GSH. GSH retains its antioxidant ability in its reduced form. GPx catalyzes the reduction of H2O2 to water using GSH as a cosubstrate. GSSG is then reduced to GSH by GSR using NADPH. The cycle between these two states aids in free radical and toxic substance metabolism. The GSH/GSSG ratio is considered a sign of the redox state and relative oxidative stress level. The capability of organisms to regenerate GSH (through the synthesis of GSH or through reduction of GSSG) means the cell’s success to withstand oxidative stress [90, 91].

The ability of GSH to act as an antioxidant is due to the thiol-containing cysteine part. GSH is located on both the first and second lines of ROS defense and requires GPx enzymes to catalyze the breakdown of H2O2 through the reduction of GSH to GSSG. GPx (GPx1), selenium-dependent, is found in the kidneys and mitochondria [92, 93]. Four other GSH peroxidases (GPx2-GPx5) have also been discovered, along with evidence of antioxidant properties in vivo [94]. Detoxified metabolites resulting from GPx defense are excreted from the cell via a glutathione S-conjugate transporter [87]. It has been reported that administration of a GSH enzyme inhibitor in rats reduces vitamin C levels in the kidney, liver, brain and lung [95]. It has been noted that GSH administration increases both vitamins C and E [96]. It is stated that vitamin C deficiency significantly decreases GSH levels in the blood [97], while vitamin C supplementation contributes to the formation of GSH [98].

4.1.3 Taurine

Cysteine can be metabolized to taurine, intracellular sulfonic acid, via cysteine-sulfinic acid. Taurine or 2-aminoethanesulfonic acid is abundant in the human body. Since there is not a carboxyl group in its structure, it is not an amino acid in theory, but it is usually referred to as proteins [99, 100]. As a result of this condition, it is released in the plasma of mammals and inside the cell [101]. Taurine is most often found where reduced O2 molecules are produced and in locations where potentially toxic substances such as xenobiotics, retinoids and bile acids are found [102]. It is also found in high levels in white blood cells and platelets [103].

Although the mechanisms of taurine’s antioxidant effects are not fully explained, possible mechanisms include regeneration of thiol groups, interfering with ROS activity and scavenging ROS [104]. It has been reported that Taurine suppresses superoxide production in mitochondria [105]. In general, taurine causes a significant reduction in ROS formation through its stimulatory effect on SOD, CAT and GPx enzyme activity [106, 107, 108]. Besides, taurine also contributes to the regulation of GSH concentrations [109]. It is thought that taurine has limited or no direct scavenging and reaction ability with ROS, and shows its antioxidant effect by increasing the activities of antioxidant enzymes such as GPx and SOD [110, 111]. It has been recorded that taurine indirectly increases endogenous GSH levels [112]. Studies have shown that taurine supplementation reduces lipid peroxidation and maintains GSH levels [113, 114].

Taurine can also inhibit free radical generation. Taurine’s amino group is the direct scavenger of hypochlorous acid (HOCl) [105]. In the presence of myeloperoxidase, taurine reacts with the acid to form a less toxic oxidant, taurine chloramine (TauCl). Since neutrophils contain high levels of taurine, TauCl formation can continue as long as there is enough taurine [115]. TauCl not only plays a role in antioxidant systems by lowering HOCl levels but also inhibits O2 production and proinflammatory mediators in neutrophils and macrophages [115, 116].

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5. Thiol status in oxidative stress-related various diseases

Thiol state and thiol-disulphide balance, which is an antioxidant defense system, may change due to oxidative stress in some diseases that may occur in various systems, organs and tissues in the organism.

5.1 Thiol status in digestive system diseases

In diseases of the digestive system, significant changes are observed in thiol state. For example, ROS formation in the liver increases due to alcohol intake. In this situation, serum protein thiol levels of alcohol drinkers decrease [117, 118]. It has also been determined that the level of thiol in the gallbladder increases in various gastrointestinal diseases [119]. A study showed that serum -SH levels of patients with helicobacter pylorus were significantly decreased [120]. Some studies have shown that native thiol (NT) and total thiol (TT) levels decrease and disulphide levels increase in celiac disease, acute pancreatitis, and inflammatory bowel disease [121, 122, 123]. In addition, the serum free thiol level has determined that non - alcoholic fatty liver disease (NAFLD) is associated with death from all causes in people with suspected NAFLD [124]. Impaired thiol-disulphide homeostasis has been reported in patients with hepatitis-B-induced chronic hepatitis and liver cirrhosis [125]. Again, in liver damage caused by pesticides, the thiol level was decreased, whereas black tea extract was found to improve thiol level in the liver tissue [126]. In experimental gastric damage induced by indomethacin, a non-steroidal anti-inflammatory drug, it was observed that ellagic acid treatment increased GSH levels and played a role in protecting against the harmful effects of indomethacin by reducing oxidative stress [127].

5.2 Thiol status in cardiovascular system diseases

Another situation in which thiol status changes is cardiovascular diseases. For example, in a study in preeclamptic patients characterized by high blood pressure, it was determined that the buffering function of SNO-albumin was impaired in patients in which the thiol of albumin acts as a scavenger for NO [128]. It was also observed that serum NT and TT levels of patients who had a heart attack decreased [129, 130]. In a study, it was determined that the level of mitochondria-specific thioredoxin increased, which increases NO bioavailability and reduces oxidative stress, thus protecting vascular endothelial cell function and preventing the development of atherosclerosis [131]. In rabbits, after experimental ischemia–reperfusion, it has been reported that thiol redox balance is impaired in myocardial cells and this causes abnormalities in cell function [132]. It has been reported that in case of cardiac damage caused by cyclophosphamide, thiol level decreases, but lupeol and its esters increase thiol level [133]. In sheep babesiosis, a tick-borne hemiparasitic disease, the parasite settles in the erythrocytes and causes a decrease in GSH levels in the blood. Therefore, the decrease in GSH levels indicates that excessive amounts of ROS are formed in cells [134].

5.3 Thiol status in nervous system diseases

In Parkinson’s disease, oxidative stress plays an important role in the degeneration of dopaminergic neurons in the substantia nigra (SN) of patients. It was determined that the thiol antioxidant glutathione (GSH) significantly decreased in the neurons present in Substantia nigra and mitochondrial damage occurred as a result of this decrease [135, 136]. It has been observed that plasma GSH, C-SH and CG-SH levels decrease in patients with schizophrenia. However, it has been observed that Curcumin administration caused a significant increase in GSH level [137, 138]. It has been determined that TT and NT concentrations are decreased in Alzheimer’s patients [139]. In the experimental Parkinson model with 6-hydroxydopamine, it was observed that the thiol level in the brain tissue decreased and the application of biarum carduchrum extract increased the thiol level [140]. In another study, hesperidin administration in 6-hydroxydopamine-induced Parkinson’s model was reported to improve thiol level in brain tissue [141].

5.4 Thiol status in urinary system diseases

Studies have shown that thiol status changes in excretory system diseases. A decrease in thiol status has been reported in chronic kidney disease [142, 143]. There was a negative correlation between serum creatine level and protein thiol level. This is an indicator that serum protein thiol level will decrease in case of renal failure [144]. It has been reported that plasma protein thiol level decreases in nephrotic syndrome [145]. In another study, it was revealed that the thiol-sulphide balance decreased and this balance shifted towards disulphide in patients with acute renal failure, and the decrease in total and native thiol concentrations was associated with the severity of the disease [146]. In renal damage induced by dimethylnitrosamine, thiol level in kidney tissue decreased, whereas Simvastatin (SMN) administration improved thiol level in kidney tissue, while Thymoquinone administration was found to have no effect on thiol level [147].

5.5 Thiol status in reproductive system diseases

In polycystic ovary syndrome study, it has been observed that native thiol, total thiol, disulphide levels in the ovary tissues of patients with polycystic ovary syndrome do not change compared to the control group [148]. It has been determined that arsenic and imidocarb reduce the total thiol level in the testicular tissue of rats with testicular damage [149]. In a study, it was concluded that chemotherapeutic agents cause ovarian damage in women and that the reduction of thiol level is very important in the mechanism of this damage [150].

5.6 Thiol status in metabolic diseases

In gestational diabetes, it was determined that pregnant women with gestational diabetes have higher disulphide/natural thiol and disulphide/total thiol levels compared to healthy pregnant women [151]. In addition, in a study, in the case of diabetic nephropathy, natural thiol and total thiol levels decreased [152]. In the pathogenesis of diabetic ketoacidosis, thiol/disulphide balance changed in favor of thiol and significant decreases in disulphide level were observed [153]. Diabetic cats have been reported to have lower erythrocyte membrane thiol level than control [154]. It has been determined that thiol/disulphide homeostasis is impaired in obesity [155].

5.7 Thiol status in respiratory system diseases

In experimental asthma disease, it was determined that inflammation in the lung tissue of rats with experimental asthma increased and thiol level decreased, On the other hand, it was determined that the application of Hydro-Ethanolic Extract of Portulaca oleracea increased thiol level [156]. It has been reported that oxidative stress occurs during acute pulmonary inflammation induced experimentally in rats and is associated with systemic thiol homeostasis [157].

5.8 Thiol status in cancer

A study in Norway shows that thiols play a preventive role against the development of the most common breast, lung, colorectal and prostate cancers [158]. It has been determined that thiol/disulphide homeostasis plays a crucial role in the pathogenesis of cervical cancer [159]. In one study, it was reported that disruption of thiol disulphide balance is likely to contribute to the etiopathogenesis of endometrial cancer [160]. In addition, it has been stated that irregularities in thiol/disulphide homeostasis may act a part in the pathogenesis of gastric cancer, and a higher oxidative stress level may cause advanced disease to become widespread and aggressive [161].

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6. Conclusion

As a result, oxidative stress can cause serious damage to the cell. Thiol is a very important antioxidant in preventing oxidative stress-induced damage and protects the cell against oxidative stress. Glutathione and taurine are among the important thiols. It is observed that thiol status changes in various diseases and thiol/disulphide homeostasis is very important in the pathogenesis of various diseases such as digestive system, respiratory system, reproductive system, urinary system, metabolic diseases and cancer. This also shows that thiol state is very important in the pathogenesis of oxidative stress-mediated diseases. Therefore, it is thought that interventions that can improve thiol status may contribute to the prevention or treatment of oxidative stress-related diseases.

References

  1. 1. Porter NA. Chemistry of lipid peroxidation. Methods Enzymol., 1984, p. 273-82. https://doi.org/10.1016/S0076-6879(84)05035-7.
  2. 2. Ozcan A, Ogun M. Biochemistry of Reactive Oxygen and Nitrogen Species. Basic Princ. Clin. Significance Oxidative Stress, InTech; 2015. https://doi.org/10.5772/61193.
  3. 3. Kara A, Gedikli S, Sengul E, Gelen V, Ozkanlar S. Oxidative Stress and Autophagy. Free Radicals Dis., 2016. https://doi.org/10.5772/64569.
  4. 4. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. 2015. https://doi.org/10.1093/acprof:oso/9780198717478.001.0001.
  5. 5. Young IS. Antioxidants in health and disease. J Clin Pathol 2001;54:176-186. https://doi.org/10.1136/jcp.54.3.176.
  6. 6. Kükürt A. Doğal bir antioksidan olarak propolis tedavisinin koruyucu etkileri. In: Evereklioğlu C, editor. Sağlık Bilim. Teor. ve Araştırmalar II, Gece Kitaplığı; 2020, p. 501-15.
  7. 7. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative Stress and Antioxidant Defense. World Allergy Organ J 2012;5:9-19. https://doi.org/10.1097/WOX.0b013e3182439613.
  8. 8. Czerska M, Mikołajewska K, Zieliński M, Gromadzińska J, Wąsowicz W. Today’s oxidative stress markers. Med Pr 2015;66:393-405. https://doi.org/10.13075/mp.5893.00137.
  9. 9. Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull 1993;49:481-493. https://doi.org/10.1093/oxfordjournals.bmb.a072625.
  10. 10. Ayala A, Muñoz MF, Argüelles S. Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxid Med Cell Longev 2014;2014:1-31. https://doi.org/10.1155/2014/360438.
  11. 11. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun 2017;482:419-425. https://doi.org/10.1016/j.bbrc.2016.10.086.
  12. 12. Romero FJ, Bosch-Morell F, Romero MJ, Jareño EJ, Romero B, Marín N, et al. Lipid peroxidation products and antioxidants in human disease. Environ Health Perspect 1998;106:1229-1234. https://doi.org/10.1289/ehp.98106s51229.
  13. 13. Davis KL, Martin E, Turko I V, Murad F. Novel effects of nitric oxide. Annu Rev Pharmacol Toxicol 2001;41:203-36.:203-36.
  14. 14. Murad F. Discovery of some of the biological effects of nitric oxide and its role in cell signaling. Biosci. Rep., vol. 24, 2004, p. 452-474. https://doi.org/10.1007/s10540-005-2741-8.
  15. 15. Hogg N. The Biochemistry and Physiology of S-nitrosothiols. Annu Rev Pharmacol Toxicol 2002;42:585-600. https://doi.org/10.1146/annurev.pharmtox.42.092501.104328.
  16. 16. Kükürt A, Kuru M, Karapehlivan M. Nitrik Oksit, Nitrik Oksit Sentaz ve Dişi Üreme Sistemindeki Rolleri. In: Evereklioğlu C, editor. Sağlık Bilim. Alanında Akad. Çalışmalar - II, Gece Kitaplığı; 2020, p. 113-23.
  17. 17. Atakisi E, Merhan O. Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities. Nitric Oxide Synthase - Simple Enzym. Roles, InTech; 2017. https://doi.org/10.5772/intechopen.68494.
  18. 18. Włodek L. Beneficial and harmful effects of thiols. Pol J Pharmacol 2002;54:215-223.
  19. 19. Rossi R, Giustarini D, Milzani A, Dalle-Donne I. Cysteinylation and homocysteinylation of plasma protein thiols during ageing of healthy human beings. J Cell Mol Med 2009;13:3131-3140. https://doi.org/10.1111/j.1582-4934.2008.00417.x.
  20. 20. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem 2014;47:326-332. https://doi.org/10.1016/j.clinbiochem.2014.09.026.
  21. 21. Turell L, Radi R, Alvarez B. The thiol pool in human plasma: The central contribution of albumin to redox processes. Free Radic Biol Med 2013;65:244-253. https://doi.org/10.1016/j.freeradbiomed.2013.05.050.
  22. 22. Cremers CM, Jakob U. Oxidant Sensing by Reversible Disulfide Bond Formation. J Biol Chem 2013;288:26489-26496. https://doi.org/10.1074/jbc.R113.462929.
  23. 23. Burton GJ, Jauniaux E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol 2011;25:287-299. https://doi.org/10.1016/j.bpobgyn.2010.10.016.
  24. 24. Alfadda AA, Sallam RM. Reactive Oxygen Species in Health and Disease. J Biomed Biotechnol 2012;2012:1-14. https://doi.org/10.1155/2012/936486.
  25. 25. Yang P, Huang S, Xu A. The Oxidative Burst System in Amphioxus. Amphioxus Immun., Elsevier; 2016, p. 153-65. https://doi.org/10.1016/B978-0-12-849903-0.00008-7.
  26. 26. Çenesiz S. The Role of Oxidant and Antioxidant Parameters in the Infectious Diseases: A Systematic Literature Review. Kafkas Univ Vet Fak Derg 2020;26:849-858. https://doi.org/10.9775/kvfd.2020.24618.
  27. 27. Seifried HE, Anderson DE, Fisher EI, Milner JA. A review of the interaction among dietary antioxidants and reactive oxygen species. J Nutr Biochem 2007;18:567-579. https://doi.org/10.1016/j.jnutbio.2006.10.007.
  28. 28. Salman KA, Ashraf S. Reactive Oxygen Species: A link between chronic inflammation and cancer. AsPac J Mol Biol Biotechnol React Oxyg Species Cancer AsPac J Mol Biol Biotechnol 2013;21:42-49.
  29. 29. Brieger K, Schiavone S, Miller J, Krause K. Reactive oxygen species: from health to disease. Swiss Med Wkly 2012;142. https://doi.org/10.4414/smw.2012.13659.
  30. 30. Kuru M, Kükürt A, Oral H, Öğün M. Clinical Use of Progesterone and Its Relation to Oxidative Stress in Ruminants. In: Drevenšek G, editor. Sex Horm. Neurodegener. Process. Dis., InTech; 2018, p. 303-27. https://doi.org/10.5772/intechopen.73311.
  31. 31. Cadenas E, Davies KJA. Mitochondrial free radical generation, oxidative stress, and aging11This article is dedicated to the memory of our dear friend, colleague, and mentor Lars Ernster (1920-1998), in gratitude for all he gave to us. Free Radic Biol Med 2000;29:222-230. https://doi.org/10.1016/S0891-5849(00)00317-8.
  32. 32. Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol 2018;16:80. https://doi.org/10.1186/s12958-018-0391-5.
  33. 33. Tu BP, Weissman JS. Oxidative protein folding in eukaryotes. J Cell Biol 2004;164:341-346. https://doi.org/10.1083/jcb.200311055.
  34. 34. Kehrer JP. The Haber–Weiss reaction and mechanisms of toxicity. Toxicology 2000;149:43-50. https://doi.org/10.1016/S0300-483X(00)00231-6.
  35. 35. Liochev SI. The Mechanism of “Fenton-Like” Reactions and Their Importance for Biological Systems. A Biologist’s View. Met. Ions Biol. Syst., Routledge; 2018, p. 1-39. https://doi.org/10.1201/9780203747605-1.
  36. 36. Moncada S, Palmer RMJ, Higgs EA. Biosynthesis of nitric oxide from l-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 1989;38:1709-1715. https://doi.org/10.1016/0006-2952(89)90403-6.
  37. 37. Bolisetty S, Jaimes E. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology. Int J Mol Sci 2013;14:6306-6344. https://doi.org/10.3390/ijms14036306.
  38. 38. Förstermann U, Sessa WC. Nitric oxide synthases: Regulation and function. Eur Heart J 2012;33. https://doi.org/10.1093/eurheartj/ehr304.
  39. 39. Drew B, Leeuwenburgh C. Aging and the Role of Reactive Nitrogen Species. Ann N Y Acad Sci 2002;959:66-81. https://doi.org/10.1111/j.1749-6632.2002.tb02084.x.
  40. 40. Kükürt A, Kuru M, Faruk Başer Ö, Karapehlivan M. Kisspeptin: Role in Female Infertility. Sex Horm. [Working Title], IntechOpen; 2020. https://doi.org/10.5772/intechopen.94925.
  41. 41. Başer ÖF, Kükürt A, Karapehlivan M. Oksidatif stresin azaltılmasında anjiyotensin dönüştürücü enzimin rolü. In: Evereklioğlu C, editor. Sağlık Bilim. Teor. ve Araştırmalar II, Gece Kitaplığı; 2020, p. 243-53.
  42. 42. Pacher P, Beckman JS, Liaudet L. Nitric Oxide and Peroxynitrite in Health and Disease. Physiol Rev 2007;87:315-424. https://doi.org/10.1152/physrev.00029.2006.
  43. 43. Van Kuijk FJGM, Holte LL, Dratz EA. 4-Hydroxyhexenal: A lipid peroxidation product derived from oxidized docosahexaenoic acid. Biochim Biophys Acta - Lipids Lipid Metab 1990;1043:116-118. https://doi.org/10.1016/0005-2760(90)90118-H.
  44. 44. Reed TT. Lipid peroxidation and neurodegenerative disease. Free Radic Biol Med 2011;51:1302-1319. https://doi.org/10.1016/j.freeradbiomed.2011.06.027.
  45. 45. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81-128. https://doi.org/10.1016/0891-5849(91)90192-6.
  46. 46. Lyons TJ. Glycation, Carbonyl Stress, EAGLEs, and the Vascular Complications of Diabetes. Semin Vasc Med 2002;2:175-190. https://doi.org/10.1055/s-2002-32041.
  47. 47. Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br J Pharmacol 2008;153:6-20. https://doi.org/10.1038/sj.bjp.0707395.
  48. 48. Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A. Protein carbonylation in human diseases. Trends Mol Med 2003;9:169-176. https://doi.org/10.1016/S1471-4914(03)00031-5.
  49. 49. Vaya J, Aviram M. Nutritional Antioxidants Mechanisms of Action, Analyses of Activities and Medical Applications. Curr Med Chem Endocr Metab Agents 2001;1:99-117. https://doi.org/10.2174/1568013013359168.
  50. 50. Biswas SK, Newby DE, Rahman I, Megson IL. Depressed glutathione synthesis precedes oxidative stress and atherogenesis in Apo-E−/− mice. Biochem Biophys Res Commun 2005;338:1368-1373. https://doi.org/10.1016/j.bbrc.2005.10.098.
  51. 51. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227-250. https://doi.org/10.1016/0891-5849(95)00017-R.
  52. 52. Ernster L, Forsmark-Andree P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig 1993;71:60-65. https://doi.org/10.1007/BF00226842.
  53. 53. Hanschmann E-M, Godoy JR, Berndt C, Hudemann C, Lillig CH. Thioredoxins, Glutaredoxins, and Peroxiredoxins—Molecular Mechanisms and Health Significance: from Cofactors to Antioxidants to Redox Signaling. Antioxid Redox Signal 2013;19:1539-1605. https://doi.org/10.1089/ars.2012.4599.
  54. 54. Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000;72:653-669. https://doi.org/10.1093/ajcn/72.2.653S.
  55. 55. Dalle–Donne I, Milzani A, Gagliano N, Colombo R, Giustarini D, Rossi R. Molecular Mechanisms and Potential Clinical Significance of S -Glutathionylation. Antioxid Redox Signal 2008;10:445-474. https://doi.org/10.1089/ars.2007.1716.
  56. 56. Prakash M, Shetty MS, Tilak P, Anwar N. Total Thiols : Biomedical Importance And Their Alteration In Various Disorders. Online J Heal Allied Sci 2009;8:1-9.
  57. 57. Dhakshinamoorthy A, Alvaro M, Garcia H. Aerobic oxidation of thiols to disulfides using iron metal–organic frameworks as solid redox catalysts. Chem Commun 2010;46:6476. https://doi.org/10.1039/c0cc02210a.
  58. 58. Giles NM, Watts AB, Giles GI, Fry FH, Littlechild JA, Jacob C. Metal and Redox Modulation of Cysteine Protein Function. Chem Biol 2003;10:677-693. https://doi.org/10.1016/S1074-5521(03)00174-1.
  59. 59. Kachur A V., Koch CJ, Biaglow JE. Mechanism of Copper-Catalyzed Oxidation of Glutathione. Free Radic Res 1998;28:259-269. https://doi.org/10.3109/10715769809069278.
  60. 60. Barron ESG. Thiol Groups of Biological Importance. Adv. Enzymol. Relat. Areas Mol. Biol., 2006, p. 201-66. https://doi.org/10.1002/9780470122563.ch4.
  61. 61. Conte M Lo, Carroll KS. The Chemistry of Thiol Oxidation and Detection. Oxidative Stress Redox Regul., Dordrecht: Springer Netherlands; 2013, p. 1-42. https://doi.org/10.1007/978-94-007-5787-5_1.
  62. 62. Winterbourn CC, Metodiewa D. Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide. Free Radic Biol Med 1999;27:322-328. https://doi.org/10.1016/S0891-5849(99)00051-9.
  63. 63. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015;14:6. https://doi.org/10.1186/1475-2891-14-6.
  64. 64. Bella DL, Hahn C, Stipanuk MH. Effects of nonsulfur and sulfur amino acids on the regulation of hepatic enzymes of cysteine metabolism. Am J Physiol Metab 1999;277:E144–E153. https://doi.org/10.1152/ajpendo.1999.277.1.E144.
  65. 65. Lee J-I, Londono M, Hirschberger LL, Stipanuk MH. Regulation of cysteine dioxygenase and γ-glutamylcysteine synthetase is associated with hepatic cysteine level. J Nutr Biochem 2004;15:112-122. https://doi.org/10.1016/j.jnutbio.2003.10.005.
  66. 66. El-Khairy L, Ueland PM, Nygård O, Refsum H, Vollset SE. Lifestyle and cardiovascular disease risk factors as determinants of total cysteine in plasma: the Hordaland Homocysteine Study. Am J Clin Nutr 1999;70:1016-1024. https://doi.org/10.1093/ajcn/70.6.1016.
  67. 67. Özkan Y, Özkan E, Şimşek B. Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease. Int J Cardiol 2002;82:269-277. https://doi.org/10.1016/S0167-5273(02)00010-4.
  68. 68. Heafield MT, Fearn S, Steventon GB, Waring RH, Williams AC, Sturman SG. Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson’s and Alzheimer’s disease. Neurosci Lett 1990;110:216-220. https://doi.org/10.1016/0304-3940(90)90814-P.
  69. 69. Park S, Imlay JA. High Levels of Intracellular Cysteine Promote Oxidative DNA Damage by Driving the Fenton Reaction. J Bacteriol 2003;185:1942-1950. https://doi.org/10.1128/JB.185.6.1942-1950.2003.
  70. 70. Laurent TC, Moore EC, Reichard P. Enzymatic Synthesis of Deoxyribonucleotides. J Biol Chem 1964;239:3436-3444. https://doi.org/10.1016/S0021-9258(18)97742-2.
  71. 71. Arnér ESJ, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000;267:6102-6109. https://doi.org/10.1046/j.1432-1327.2000.01701.x.
  72. 72. Takagi Y, Mitsui A, Nishiyama A, Nozaki K, Sono H, Gon Y, et al. Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage. Proc Natl Acad Sci 1999;96:4131-4136. https://doi.org/10.1073/pnas.96.7.4131.
  73. 73. Mustacich D, Powis G. Thioredoxin reductase. Biochem J 2000;346:1. https://doi.org/10.1042/0264-6021:3460001.
  74. 74. Monteiro HP, Ogata FT, Stern A. Thioredoxin promotes survival signaling events under nitrosative/oxidative stress associated with cancer development. Biomed J 2017;40:189-199. https://doi.org/10.1016/j.bj.2017.06.002.
  75. 75. Holmgren A. Thioredoxin and Glutaredoxin Systems. J Biol Chem 1989;264:13963-13966. https://doi.org/10.1016/S0021-9258(18)71625-6.
  76. 76. Nordberg J, Arnér ESJ. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 2001;31:1287-1312. https://doi.org/10.1016/S0891-5849(01)00724-9.
  77. 77. Arnér ESJ, Nordberg J, Holmgren A. Efficient Reduction of Lipoamide and Lipoic Acid by Mammalian Thioredoxin Reductase. Biochem Biophys Res Commun 1996;225:268-274. https://doi.org/10.1006/bbrc.1996.1165.
  78. 78. Andersson M, Holmgren A, Spyrou G. NK-lysin, a Disulfide-containing Effector Peptide of T-lymphocytes, Is Reduced and Inactivated by Human Thioredoxin Reductase. J Biol Chem 1996;271:10116-10120. https://doi.org/10.1074/jbc.271.17.10116.
  79. 79. May JM, Mendiratta S, Hill KE, Burk RF. Reduction of Dehydroascorbate to Ascorbate by the Selenoenzyme Thioredoxin Reductase. J Biol Chem 1997;272:22607-22610. https://doi.org/10.1074/jbc.272.36.22607.
  80. 80. Casso D, Beach D. A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeast. MGG Mol Gen Genet 1996;252:518. https://doi.org/10.1007/s004380050259.
  81. 81. Arnér ESJ. Focus on mammalian thioredoxin reductases — Important selenoproteins with versatile functions. Biochim Biophys Acta - Gen Subj 2009;1790:495-526. https://doi.org/10.1016/j.bbagen.2009.01.014.
  82. 82. Whayne TF, Parinandi N, Maulik N. Thioredoxins in cardiovascular disease. Can J Physiol Pharmacol 2015;93:903-911. https://doi.org/10.1139/cjpp-2015-0105.
  83. 83. Rhee SG, Chae HZ, Kim K. Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med 2005;38:1543-1552. https://doi.org/10.1016/j.freeradbiomed.2005.02.026.
  84. 84. Matsuo Y, Yodoi J. Extracellular thioredoxin: A therapeutic tool to combat inflammation. Cytokine Growth Factor Rev 2013;24:345-353. https://doi.org/10.1016/j.cytogfr.2013.01.001.
  85. 85. Saitoh M. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 1998;17:2596-2606. https://doi.org/10.1093/emboj/17.9.2596.
  86. 86. Nakamura H, Masutani H, Yodoi J. Extracellular thioredoxin and thioredoxin-binding protein 2 in control of cancer. Semin Cancer Biol 2006;16:444-451. https://doi.org/10.1016/j.semcancer.2006.09.001.
  87. 87. Hayes JD, McLellan LI. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res 1999;31:273-300. https://doi.org/10.1080/10715769900300851.
  88. 88. Maher P, Lewerenz J, Lozano C, Torres JL. A novel approach to enhancing cellular glutathione levels. J Neurochem 2008;107:690-700. https://doi.org/10.1111/j.1471-4159.2008.05620.x.
  89. 89. Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C. Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 2005;16:577-586. https://doi.org/10.1016/j.jnutbio.2005.05.013.
  90. 90. Curtin JF, Donovan M, Cotter TG. Regulation and measurement of oxidative stress in apoptosis. J Immunol Methods 2002;265:49-72. https://doi.org/10.1016/S0022-1759(02)00070-4.
  91. 91. Jones DP. Redox potential of GSH/GSSG couple: Assay and biological significance. Methods Enzymol., 2002, p. 93-112. https://doi.org/10.1016/S0076-6879(02)48630-2.
  92. 92. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical Role as a Component of Glutathione Peroxidase. Science (80- ) 1973;179:588-90. https://doi.org/10.1126/science.179.4073.588.
  93. 93. Esworthy RS, Ho Y-S, Chu F-F. The Gpx1 Gene Encodes Mitochondrial Glutathione Peroxidase in the Mouse Liver. Arch Biochem Biophys 1997;340:59-63. https://doi.org/10.1006/abbi.1997.9901.
  94. 94. Arai M, Imai H, Koumura T, Yoshida M, Emoto K, Umeda M, et al. Mitochondrial Phospholipid Hydroperoxide Glutathione Peroxidase Plays a Major Role in Preventing Oxidative Injury to Cells. J Biol Chem 1999;274:4924-4933. https://doi.org/10.1074/jbc.274.8.4924.
  95. 95. Mãrtensson J, Meister A. Glutathione deficiency decreases tissue ascorbate levels in newborn rats: Ascorbate spares glutathione and protects. Proc Natl Acad Sci U S A 1991;88:4656-4660. https://doi.org/10.1073/pnas.88.11.4656.
  96. 96. Chan AC, Tran K, Raynor T, Ganz P, Chow CK. Regeneration of vitamin E in human platelets. Free Radic Biol Med 1990;9:11. https://doi.org/10.1016/0891-5849(90)90206-X.
  97. 97. Henning SM, Zhang JZ, McKee RW, Swendseid ME, Jacob RA. Glutathione Blood Levels and Other Oxidant Defense Indices in Men Fed Diets Low in Vitamin C. J Nutr 1991;121:1969-1975. https://doi.org/10.1093/jn/121.12.1969.
  98. 98. Johnston CS, Meyer CG, Srilakshmi JC. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr 1993;58:103-105. https://doi.org/10.1093/ajcn/58.1.103.
  99. 99. Kendler BS. Taurine: An overview of its role in preventive medicine. Prev Med (Baltim) 1989;18:79-100. https://doi.org/10.1016/0091-7435(89)90056-X.
  100. 100. Geggel HS, Ament ME, Heckenlively JR, Martin DA, Kopple JD. Nutritional Requirement for Taurine in Patients Receiving Long-Term Parenteral Nutrition. N Engl J Med 1985;312:142-146. https://doi.org/10.1056/NEJM198501173120302.
  101. 101. Brosnan JT, Brosnan ME. The Sulfur-Containing Amino Acids: An Overview. J Nutr 2006;136:1636S–1640S. https://doi.org/10.1093/jn/136.6.1636S.
  102. 102. Wright CE, Tallan HH, Lin YY. Taurine: Biological Update. Annu Rev Biochem 1986;55:427-453. https://doi.org/10.1146/annurev.bi.55.070186.002235.
  103. 103. Franconi F, Di Leo MAS, Bennardini F, Ghirlanda G. Is Taurine Beneficial in Reducing Risk Factors for Diabetes Mellitus? Neurochem Res 2004;29:143-150. https://doi.org/10.1023/B:NERE.0000010443.05899.2f.
  104. 104. Imae M, Asano T, Murakami S. Potential role of taurine in the prevention of diabetes and metabolic syndrome. Amino Acids 2014;46:81-88. https://doi.org/10.1007/s00726-012-1434-4.
  105. 105. Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 2009;87:91-99. https://doi.org/10.1139/Y08-110.
  106. 106. Wang G, Li W, Lu X, Zhao X, Xu L. Taurine attenuates oxidative stress and alleviates cardiac failure in type I diabetic rats. Croat Med J 2013;54:171-179. https://doi.org/10.3325/cmj.2013.54.171.
  107. 107. Shivananjappa MM, Muralidhara. Taurine attenuates maternal and embryonic oxidative stress in a streptozotocin-diabetic rat model. Reprod Biomed Online 2012;24:558-566. https://doi.org/10.1016/j.rbmo.2012.01.016.
  108. 108. Rashid K, Das J, Sil PC. Taurine ameliorate alloxan induced oxidative stress and intrinsic apoptotic pathway in the hepatic tissue of diabetic rats. Food Chem Toxicol 2013;51:317-329. https://doi.org/10.1016/j.fct.2012.10.007.
  109. 109. Kim YG, Kim SK, Kwon JW, Park OJ, Kim SG, Kim YC, et al. Effects of cysteine on amino acid concentrations and transsulfuration enzyme activities in rat liver with protein–calorie malnutrition. Life Sci 2003;72:1171-1181. https://doi.org/10.1016/S0024-3205(02)02366-4.
  110. 110. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J 1988;256:251-255. https://doi.org/10.1042/bj2560251.
  111. 111. Vohra BPS, Hui X. Taurine Protects against Carbon Tetrachloride Toxicity in the Cultured Neurons and In Vivo. Arch Physiol Biochem 2001;109:90-94. https://doi.org/10.1076/apab.109.1.90.4287.
  112. 112. Noeman SA, Hamooda HE, Baalash AA. Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats. Diabetol Metab Syndr 2011;3:17. https://doi.org/10.1186/1758-5996-3-17.
  113. 113. Anand P, Rajakumar D, Jeraud M, William Fe AJ, Balasubram T. Effects of Taurine on Glutathione Peroxidase, Glutathione Reductase and Reduced Glutathione Levels in Rats. Pakistan J Biol Sci 2011;14:219-225. https://doi.org/10.3923/pjbs.2011.219.225.
  114. 114. Oudit GY, Trivieri MG, Khaper N, Husain T, Wilson GJ, Liu P, et al. Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model. Circulation 2004;109:1877-1885. https://doi.org/10.1161/01.CIR.0000124229.40424.80.
  115. 115. Schuller-Levis GB, Park E. Taurine and Its Chloramine: Modulators of Immunity. Neurochem Res 2004;29:117-126. https://doi.org/10.1023/B:NERE.0000010440.37629.17.
  116. 116. Marcinkiewicz J, Grabowska A, Bereta J, Stelmaszynska T. Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators. J Leukoc Biol 1995;58:667-674. https://doi.org/10.1002/jlb.58.6.667.
  117. 117. Prakash M, K. Shetty J, Tripathy S, Verma M, Vasudev S, V. Bhandar P. Serum Total Thiol Status in Alcohol Abusers. Asian J Biochem 2007;3:48-51. https://doi.org/10.3923/ajb.2008.48.51.
  118. 118. Venkatraman A, Landar A, Davis AJ, Ulasova E, Page G, Murphy MP, et al. Oxidative modification of hepatic mitochondria protein thiols: effect of chronic alcohol consumption. Am J Physiol Liver Physiol 2004;286:G521–G527. https://doi.org/10.1152/ajpgi.00399.2003.
  119. 119. Yılmaz İA, Akçay T, Çakatay U, Telci A, Ataus S, Yalçın V. Relation between bladder cancer and protein oxidation. Int Urol Nephrol 2003;35:345-350. https://doi.org/10.1023/B:UROL.0000022920.93994.ba.
  120. 120. Aslan M, Nazligul Y, Horoz M, Bolukbas C, Bolukbas FF, Gur M, et al. Serum paraoxonase-1 activity in Helicobacter pylori infected subjects. Atherosclerosis 2008;196:270-274. https://doi.org/10.1016/j.atherosclerosis.2006.10.024.
  121. 121. Kaplan M, Ates I, Yuksel M, Ozin YO, Alisik M, Erel O, et al. Thiol/disulphide homeostasis in celiac disease. World J Gastrointest Pharmacol Ther 2017;8:120. https://doi.org/10.4292/wjgpt.v8.i2.120.
  122. 122. Yuksel M, Ates I, Kaplan M, Alışık M, Erel Ö, Saygılı F, et al. The dynamic thiol/disulphide homeostasis in inflammatory bowel disease and its relation with disease activity and pathogenesis. Int J Colorectal Dis 2016;31:1229-1231. https://doi.org/10.1007/s00384-015-2439-8.
  123. 123. Koseoglu H, Alisik M, Basaran M, Tayfur Yurekli O, Solakoglu T, Tahtaci M, et al. Dynamic thiol/disulphide homeostasis in acute pancreatitis. Turkish J Gastroenterol 2018:348-453. https://doi.org/10.5152/tjg.2018.17499.
  124. 124. Damba T, Bourgonje AR, Abdulle AE, Pasch A, Sydor S, Berg EH, et al. Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population. Liver Int 2020;40:2148-2159. https://doi.org/10.1111/liv.14562.
  125. 125. Dertli R, Keskin M, Bıyık M, Ataseven H, Polat H, Demir A, et al. Dynamic thiol-disulfide homeostasis is disturbed in hepatitis B virus-related chronic hepatitis and liver cirrhosis. TURKISH J Med Sci 2018;48:985-992. https://doi.org/10.3906/sag-1803-135.
  126. 126. Khan SM. Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury. Cell Biochem Funct 2006;24:327-332. https://doi.org/10.1002/cbf.1246.
  127. 127. Kaya İ, Kaya MM, Kükürt A, Özcan A, Karaman M, Deveci HA, et al. Effect of Ellagic Acid on Some Oxidative Stress Parameters and Cyclooxygenase-2 Reactivity in Mice with Experimental Gastric Injury. Japanese J Gastroenterol Hepatol 2019;2:1-9.
  128. 128. Gandley RE, Tyurin VA, Huang W, Arroyo A, Daftary A, Harger G, et al. S -Nitrosoalbumin–Mediated Relaxation Is Enhanced by Ascorbate and Copper. Hypertension 2005;45:21-27. https://doi.org/10.1161/01.HYP.0000150158.42620.3e.
  129. 129. Altıparmak IH, Erkuş ME, Sezen H, Demirbag R, Gunebakmaz O, Kaya Z, et al. The relation of serum thiol levels and thiol/disulphide homeostasis with the severity of coronary artery disease. Kardiol Pol 2016:1346-1353. https://doi.org/10.5603/KP.a2016.0085.
  130. 130. Kundi H, Ates I, Kiziltunc E, Cetin M, Cicekcioglu H, Neselioglu S, et al. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med 2015;33:1567-1571. https://doi.org/10.1016/j.ajem.2015.06.016.
  131. 131. Patwari P, Lee RT. Thioredoxins, Mitochondria, and Hypertension. Am J Pathol 2007;170:805-808. https://doi.org/10.2353/ajpath.2007.061243.
  132. 132. Ceconi C. New insights on myocardial pyridine nucleotides and thiol redox state in ischemia and reperfusion damage. Cardiovasc Res 2000;47:586-594. https://doi.org/10.1016/S0008-6363(00)00104-8.
  133. 133. Sudharsan PT, Mythili Y, Selvakumar E, Varalakshmi P. Lupeol and its ester ameliorate the cyclophosphamide provoked cardiac lysosomal damage studied in rat. Mol Cell Biochem 2006;282:23-29. https://doi.org/10.1007/s11010-006-1169-1.
  134. 134. Deveci HA, Nur G, Kukurt A. Biochemical and histopathological changes of babesiosis in naturally infected sheep in gaziantep region. Fresenius Environ Bull 2017;26:4883-4889.
  135. 135. Jagatha B, Mythri RB, Vali S, Bharath MMS. Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: Therapeutic implications for Parkinson’s disease explained via in silico studies. Free Radic Biol Med 2008;44:907-917. https://doi.org/10.1016/j.freeradbiomed.2007.11.011.
  136. 136. Anderson CC, Marentette JO, Rauniyar AK, Prutton KM, Khatri M, Matheson C, et al. Maneb alters central carbon metabolism and thiol redox status in a toxicant model of Parkinson’s disease. Free Radic Biol Med 2021;162:65-76. https://doi.org/10.1016/j.freeradbiomed.2020.11.028.
  137. 137. Dietrich-Muszalska A, Olas B, Głowacki R, Bald E. Oxidative/Nitrative Modifications of Plasma Proteins and Thiols from Patients with Schizophrenia. Neuropsychobiology 2009;59:1-7. https://doi.org/10.1159/000202822.
  138. 138. Fendri C, Mechri A, Khiari G, Othman A, Kerkeni A, Gaha L. Implication du stress oxydant dans la physiopathologie de la schizophrénie: revue de la literature. Encephale 2006;32:244-252. https://doi.org/10.1016/S0013-7006(06)76151-6.
  139. 139. Gumusyayla S, Vural G, Bektas H, Deniz O, Neselioglu S, Erel O. A novel oxidative stress marker in patients with Alzheimer’s disease: dynamic thiol–disulphide homeostasis. Acta Neuropsychiatr 2016;28:315-320. https://doi.org/10.1017/neu.2016.13.
  140. 140. Zanganehnejad Z, Setorki M. Effect of Biarum carduchrum extract on brain tissue thiol level in rat model of 6-hydroxydopamine-induced Parkinson’s disease. J Herbmed Pharmacol 2018;7:136-140. https://doi.org/10.15171/jhp.2018.23.
  141. 141. Antunes MS, Goes ATR, Boeira SP, Prigol M, Jesse CR. Protective effect of hesperidin in a model of Parkinson’s disease induced by 6-hydroxydopamine in aged mice. Nutrition 2014;30:1415-1422. https://doi.org/10.1016/j.nut.2014.03.024.
  142. 142. Galle J. Oxidative stress in chronic renal failure. Nephrol Dial Transplant 2001;16:2135-2137. https://doi.org/10.1093/ndt/16.11.2135.
  143. 143. Himmelfarb J, Hakim RM. Oxidative stress in uremia. Curr Opin Nephrol Hypertens 2003;12:593-598. https://doi.org/10.1097/00041552-200311000-00004.
  144. 144. Prakash M, Shetty J, Rao L, Sharma S, Rodrigues A, Prabhu R. Serum paraoxonase activity and protein thiols in chronic renal failure patients. Indian J Nephrol 2008;18:13. https://doi.org/10.4103/0971-4065.41282.
  145. 145. Karthikeyan K, Sinha I, Prabhu K, Bhaskaranand N, Rao A. Plasma Protein Thiols and Total Antioxidant Power in Pediatric Nephrotic Syndrome. Nephron Clin Pract 2008;110:c10–c14. https://doi.org/10.1159/000148210.
  146. 146. Otal Y, Demircan S, Sener A, Alısık M, Tanrıverdi F, Haydar FGE, et al. Acute Renal Failure and Thiol-Disulfide Homeostasis. J Nephrol Ther 2018;08. https://doi.org/10.4172/2161-0959.1000312.
  147. 147. Saricicek E, Celik A, Uremis N, Kilinc M. Protective effects of simvastatin, Nigella sativa oil and thmoquinone against dimethylnitrosamine-induced oxidative stress in rat kidney. Biomed Res 2016;27.
  148. 148. Aydın GA, Turan Özsoy HG, Ankaralı H, Özgen G, Neşelioğlu S. The association of dynamic thiol-disulfide homeostasis and inflammatory markers in patients with polycystic ovary syndrome. Taiwan J Obstet Gynecol 2020;59:79-84. https://doi.org/10.1016/j.tjog.2019.11.012.
  149. 149. Mahajan L, Verma PK, Raina R, Sood S. Potentiating effect of imidacloprid on arsenic-induced testicular toxicity in Wistar rats. BMC Pharmacol Toxicol 2018;19:48. https://doi.org/10.1186/s40360-018-0239-9.
  150. 150. Spears N, Lopes F, Stefansdottir A, Rossi V, De Felici M, Anderson RA, et al. Ovarian damage from chemotherapy and current approaches to its protection. Hum Reprod Update 2019;25:673-693. https://doi.org/10.1093/humupd/dmz027.
  151. 151. Gürlek B, Alan M, Çolak S, Önal Ö, Erel Ö, Biçer C. Dynamic thiol/disulfide homeostasis in gestational diabetes mellitus: Is it related with adverse perinatal outcomes? Med Sci Discov 2019;6:198-204. https://doi.org/10.36472/msd.v6i9.293.
  152. 152. Eren MA, Koyuncu İ, İncebıyık H, Karakaş H, Erel Ö, Sabuncu T. The evaluation of thiol/disulphide homeostasis in diabetic nephropathy. Diabetes Res Clin Pract 2019;148:249-253. https://doi.org/10.1016/j.diabres.2019.01.022.
  153. 153. Otal Y, Kahraman FA, Haydar FG, Erel Ö. Dynamic thiol/disulphide homeostasis as oxidative stress marker in diabetic ketoacidosis. TURKISH J Med Sci 2021. https://doi.org/10.3906/sag-1904-55.
  154. 154. Zini E, Gabai G, Salesov E, Gerardi G, Da Dalt L, Lutz TA, et al. Oxidative status of erythrocytes, hyperglycemia, and hyperlipidemia in diabetic cats. J Vet Intern Med 2020;34:616-625. https://doi.org/10.1111/jvim.15732.
  155. 155. Mengen E, Uçaktürk SA, Kocaay P, Kaymaz Ö, Neşelioğlu S, Erel Ö. The Significance of Thiol/Disulfide Homeostasis and Ischemia-modified Albumin Levels in Assessing Oxidative Stress in Obese Children and Adolescents. J Clin Res Pediatr Endocrinol 2020;12:45-54. https://doi.org/10.4274/jcrpe.galenos.2019.2019.0039.
  156. 156. Boskabady MH, Kaveh M, Shakeri F, Mohammadian Roshan N, Rezaee R. Hydro-ethanolic extract of portulaca oleracea ameliorates total and differential wbc, lung pathology and oxidative biomarkers in asthmatic rats. Iran J Pharm Res 2019;18:1947-1958. https://doi.org/10.22037/ijpr.2019.13712.11817.
  157. 157. Cotgreave IA, Johansson U, Moldéus P, Brattsand R. Lung and systematic thiol homeostasis during an acute lung inflammation in the rat. Toxicology 1988;50:331-343. https://doi.org/10.1016/0300-483X(88)90048-0.
  158. 158. Gào X, Wilsgaard T, Jansen EHJM, Xuan Y, Anusruti A, Brenner H, et al. Serum total thiol levels and the risk of lung, colorectal, breast and prostate cancer: A prospective case–cohort study. Int J Cancer 2020;146:1261-1267. https://doi.org/10.1002/ijc.32428.
  159. 159. Sezgin B, Kinci MF, Pirinççi F, Camuzcuoğlu A, Erel Ö, Neşelioğlu S, et al. <scp>Thiol-disulfide</scp> status of patients with cervical cancer. J Obstet Gynaecol Res 2020;46:2423-2429. https://doi.org/10.1111/jog.14480.
  160. 160. Sezgin B, Pirinççi F, Camuzcuoğlu A, Erel Ö, Neşelioğlu S, Camuzcuoğlu H. Assessment of thiol disulfide balance in early-stage endometrial cancer. J Obstet Gynaecol Res 2020;46:1140-1147. https://doi.org/10.1111/jog.14301.
  161. 161. Hizal M, Sendur MAN, Bilgin B, Akinci MB, Dede DS, Neselioglu S, et al. Evaluation of dynamic serum thiol/disulfide homeostasis in locally advanced and metastatic gastric cancer. J Oncol Sci 2018;4:1-4. https://doi.org/10.1016/j.jons.2018.01.002.

Written By

Abdulsamed Kükürt, Volkan Gelen, Ömer Faruk Başer, Haci Ahmet Deveci and Mahmut Karapehlivan

Submitted: 17 January 2021 Reviewed: 17 February 2021 Published: 20 March 2021