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![Condensed structural chemical formula of glutathione (IUPAC name: (2S)-2-amino-4-{[(1R)1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl] carbamoyl}butanoic acid).](publication/324812000/figure/fig1/AS:620197035638784@1524877904920/Condensed-structural-chemical-formula-of-glutathione-IUPAC-name.png)
Condensed structural chemical formula of glutathione (IUPAC name: (2S)-2-amino-4-{[(1R)1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl] carbamoyl}butanoic acid).
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Which scientist has never heard of glutathione (GSH)? This well-known low-molecular-weight tripeptide is perhaps the most famous natural antioxidant. However, the interest in GSH should not be restricted to its redox properties. This multidisciplinary review aims to bring out some lesser-known aspects of GSH, for example, as an emerging tool in nan...
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Citations
... Glutathione has thiol groups' antioxidant characteristics because it can be oxidized and reduced reversibly and has a thiol group in its system [138]. Glutathione is a cellular antioxidant because of its importance in maintaining the cell's redox state and its high concentration. ...
Absorption of free radicals in the body cannot be done by antioxidant compounds originating from the human body, so exogenous antioxidants are required to help in their natural antioxidant action. Oxidative stress can be caused by an imbalance of free radical inhibitors and the accumulation of free radicals that enter cellular structures. Synthetic antioxidants found in external antioxidants are not the primary choice because they are harmful and carcinogenic. Therefore, using natural ingredients provides a necessary alternative to constructing novel natural antioxidants. Recent studies have highlighted critical analysis and evaluation that flavonoids are a unique class of secondary metabolites found in plants and used in communities as traditional therapeutics with proven bioactivity. This could support new discoveries based on various herbal medicines and in addition, the functional effectiveness of flavonoids as antioxidants against free radicals. In this review, there are several strengths in the discussion. First, the study takes a comprehensive approach by covering various aspects, including the properties and sources of free radicals, oxidative stress in relation to different diseases, antioxidant defense mechanisms, and the specific antioxidant mechanisms of flavonoids. Second, the focus on natural antioxidants, especially flavonoids, and also discussion about clinical applications and human studies, limitations, global perspectives, and future research directions of flavonoids compounds become references in the selection of natural medicines. But, several constraints should be considered when interpreting the findings of this review. First, the discussion about the mechanism of antioxidant compounds is only discussed in general and only takes one example of a compound (flavonoid) that has the potential as an antioxidant. Second, the lack of findings regarding the relationship between several diseases discussed with free radicals. Third, a limited number of studies investigated regarding clinical applications and human studies of some of the diseases discussed.
... Also, free amino acids detected through the digestion process are known to have a positive effect on enhancing the antioxidant activity of enzymes. Most glutathione is synthesized between cells, and the reduced form of glutathione protects cells by reducing active oxygen (Dringen and Hamprecht, 1999;Gaucher et al., 2018;Levy et al., 1993;Piste, 2013). Lysine can increase the ability to free radical scavenging to protect against oxidative damage by upregulating the expression of antioxidant enzyme genes (Li, 2016). ...
This study was conducted to compare and analyze the changes in the biochemical characteristics and biological activity of peptide extracts derived from Chickso, Hanwoo, and Wagyu beef during digestion. The results of the in vitro digestion analysis revealed that the digestion rate, total free amino acid content, and antioxidant and antihypertensive activities of Chickso loin and shank myofibrillar proteins were significantly higher (p<0.05) than those of Hanwoo and Wagyu loin and shank myofibrillar proteins. Particularly, the peptide extracts of Chickso loin and shank had a high angiotensin-converting enzyme inhibitory activity. In mice in vivo digestion experiment, the blood serum of mice fed with Chickso loin peptide extract (<10 kDa) showed the highest antioxidant enzyme activity. Thus, Chickso peptide extracts were deemed to be similar or more bioactive than Hanwoo and Wagyu peptide extracts, and can be used as bioactive materials.
... 47 GSH can engulf free radicals and ROS directly or enzymatically. 48 In the enzymatic pathway, GSH brings about the reduction of H 2 O 2 into water and lipid peroxide into lipid alcohol being employed as a co-substrate of GPX. 49 Moreover, GSH detoxifies the other electron-deficient xenobiotics (X) through direct conjugation with them, forming GS-X adducts upon catalytic action of glutathione S-transferase (GST), 50,51 and then cells thrust them out with the help of the multidrug resistance-associated protein 1 (MRP1) efflux pump. ...
The cellular defense system against exogenous substances makes therapeutics inefficient as intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS) or reactive nitrogen species (RNS) or other free radicals produced by the therapeutics. In the cancer cell microenvironment, the intracellular GSH level becomes exceptionally high to fight against oxidative stress created by the production of ROS/RNS or any free radicals, which are the byproducts of intracellular redox reactions or cellular respiration processes. Thus, in order to maintain redox homeostasis for survival of cancer cells and their rapid proliferation, the GSH level starts to escalate. In this circumstance, the administration of anticancer therapeutics is in vain, as the elevated GSH level reduces their potential by reduction or by scavenging the ROS/RNS they produce. Therefore, in order to augment the therapeutic potential of anticancer agents against elevated GSH condition, the GSH level must be depleted by hook or by crook. Hence, this Review aims to compile precisely the role of GSH in cancer cells, the importance of its depletion for cancer therapy and examples of anticancer activity of a few selected metal complexes which are able to trigger cancer cell death by depleting the GSH level.
... There are many strategies to overcome the limitation of BBB. For example, glutathione (GSH) can be used as a targeting molecule to help its coupled particles penetrate the BBB by transcellular pathway, since the sodium-dependent glutathione transporter is widely expressed [32][33][34]. Moreover, focused ultrasound (FUS) with low intensity can temporarily, reversibly and safely open the BBB via the cavitation effect after intravenously injecting exogenous microbubbles (MBs) [35]. ...
... GSH is a tripeptide that plays an important role in redox homeostasis and antioxidant defense [47,48]. When supplied from outside, GSH cannot be directly absorbed into cells but must be metabolized into free amino acids that can enter the cell by specific transporters [49]. Thus, it is difficult to define the mechanism of action of external GSH, whether it is direct or indirect, although several clinical studies have reported that administration of GSH or glutathione disulfide (GSSG) in different routes alleviates melasma and hyperpigmentation [11]. ...
The total melanin synthesis in the skin depends on various melanogenic factors, including the number of viable melanocytes, the level of melanogenic enzymes per cell, and the reaction rate of the enzymes. The purpose of this study is to examine the effects of L-cysteine (L-Cys), L-ascorbic acid (L-AA), and their derivatives on the tyrosinase (TYR) activity and autoxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) in vitro and the viability and melanin synthesis of B16/F10 cells under different conditions. L-Cysteinamide (C-NH2), glutathione (GSH), L-Cys, L-AA, and N-acetyl L-cysteine (NAC) inhibited the catalytic activity of TYR in vitro. L-AA, C-NH2, L-ascorbic acid 2-O-glucoside (AAG), and 3-O-ethyl L-ascorbic acid (EAA) inhibited the autoxidation of L-DOPA in vitro. L-DOPA exhibited cytotoxicity at 0.1 mM and higher concentrations, whereas L-tyrosine (L-Tyr) did not affect cell viability up to 3 mM. L-AA, magnesium L-ascorbyl 2-phosphate (MAP), and L-Cys attenuated the cell death induced by L-DOPA. C-NH2 decreased the intracellular melanin level at the basal state, whereas L-AA, MAP, and AAG conversely increased it. C-NH2 reduced the number of darkly pigmented cells via in situ L-DOPA staining, whereas L-AA, MAP, GSH, and AAG increased it. C-NH2 decreased the intracellular melanin level at the alpha-melanocyte-stimulating hormone (α-MSH)-stimulated state, while NAC and GSH increased it. L-AA and C-NH2 decreased the intracellular melanin level at the L-Tyr-stimulated state, but NAC and GSH increased it. L-Ascorbyl tetraisopalmitate (ATI) showed no or minor effects in most experiments. This study suggests that L-AA can either promote or inhibit the different melanogenic factors, and C-NH2 can inhibit the multiple melanogenic factors consistently. This study highlights the multifaceted properties of L-Cys, L-AA, and their derivatives that can direct their therapeutic applications in hyperpigmentation, hypopigmentation, or both disorders.
... Indeed, antioxidants are necessary to inhibit the generation of new free radicals to stop oxidative stress, and the administration of exogenous antioxidant chemicals can prevent ROSs from exerting their harmful effects [55]. For instance, several studies have reported the antioxidant effects of NAC [13,56], VitD3 [57,58], and Glut [59,60], highlighting their significant contributions to enhancing the mechanisms responsible for maintaining body homeostasis and safeguarding the health of body tissues. The data collected in this study demonstrate that the combination of NAC, VitD3, and Glut exerts a cooperative effect in all body districts analysed, indicating a possible new strategy to restore oxidative homeostasis of the body. ...
Chronic oxidative stress has been consistently linked to age-related diseases, conditions, and degenerative syndromes. Specifically, the brain is the organ that significantly contributes to declining quality of life in ageing. Since the body cannot completely counteract the detrimental effects of oxidative stress, nutraceuticals’ antioxidant properties have received significant attention in recent years. This study assesses the potential health benefits of a novel combination of glutathione, vitamin D3, and N-acetylcysteine. To examine the combination’s absorption and biodistribution and confirm that it has no harmful effects, the bioavailability of the mixture was first evaluated in a 3D model that mimicked the intestinal barrier. Further analyses on the blood–brain barrier was conducted to determine the antioxidant effects of the combination in the nervous system. The results show that the combination reaches the target and successfully crosses the blood–brain and intestinal barriers, demonstrating enhanced advantages on the neurological system, such as a reduction (about 10.5%) in inflammation and enhancement in cell myelination (about 20.4%) and brain tropism (about 18.1%) compared to the control. The results support the cooperative effect of N-acetylcysteine, vitamin D3, and glutathione to achieve multiple health benefits, outlining the possibility of an alternative nutraceutical approach.
... This phenomenon may be attributed to the excessive production of ROS inhibiting or damaging the ciliates oxidative defense system. Moreover, our study also explored alterations in the levels of reduced glutathione (GSH) in ciliates, which is a key measure of the organism antioxidant capacity (Liu et al., 2010;Gaucher et al., 2018;Niu et al., 2021). In normal cells, approximately 90 % of glutathione exists in its reduced form. ...
... It played its antioxidant role as a scavenger of ROS. Moreover, GSH played a pro-oxidant role, which had a lesser efficacy than its antioxidant role (Gaucher et al. 2018). On other side, catalase (CAT) considered as one of the first line defense antioxidant enzymes. ...
Dramatic metabolic changes during pregnancy and post-partum period resulted in alteration of the biochemical parameters in dromedary she-camels. The current study focused on assessment of stress indicators in post-partum dromedary she-camels on days 14, 28 and 42 post-calving through monitoring the clinical findings, serum steroid hormones, serum or milk oxidant/antioxidant indicators, and milk somatic cell count (SCC) status with reference to serum lipid profile changes. The study also stated several correlations between reproductive cyclicity parameters, stress biomarkers and serum-milk oxidant/antioxidant indicators. The study was conducted on clinically healthy recently calved she-camels (n = 25). They were subjected to clinical and laboratory assays including lipid profiles, serum steroid hormones [Progesterone (P4) and estradiol (E2)], serum or milk oxidant/antioxidant biomarkers [Malondialdehyde (MDA), reduced glutathione (GSH) and cortisol], and milk SCC on days 14, 21 and 28 post-calving. The study concluded the influence of stress as a result of lactation in post-partum period in recently calved she-camels and its relationship with reproductive cyclicity as well as changes in serum steroids, lipid profiles, serum-milk oxidant/antioxidants parameters, and milk SCC that was reflected through significant elevations in serum levels of P4, E2, cortisol, MDA and glucose, and milk values of MDA, cortisol and SCC as well as significant drop in serum levels of GSH, TPs, albumins and globulins on day 14 post-calving comparing with their values particularly on day 42. The study stated variable correlation relationships between reproductive cyclicity parameters, lipid profiles, serum-milk oxidant/antioxidants parameters and milk SCC.
... Of the remaining 13 genes, 6 are glutathione transferase genes (GSTs). Glutathione (GSH) is a powerful endogenous antioxidant [51]. In humans, GSH blood concentration can be used as a biomarker for oxidative damage protection [52]. ...
Heat stress results in significant economic losses to the poultry industry. Genetics plays an important role in chickens adapting to the warm environment. Physiological parameters such as hematochemical parameters change in response to heat stress in chickens. To explore the genetics of heat stress resilience in chickens, a genome-wide association study (GWAS) was conducted using Hy-Line Brown layer chicks subjected to either high ambient temperature or combined high temperature and Newcastle disease virus infection. Hematochemical parameters were measured during three treatment phases: acute heat stress, chronic heat stress, and chronic heat stress combined with NDV infection. Significant changes in blood parameters were recorded for 11 parameters (sodium (Na+, potassium (K+), ionized calcium (iCa2+), glucose (Glu), pH, carbon dioxide partial pressure (PCO2), oxygen partial pressure (PO2), total carbon dioxide (TCO2), bicarbonate (HCO3), base excess (BE), and oxygen saturation (sO2)) across the three treatments. The GWAS revealed 39 significant SNPs (p < 0.05) for seven parameters, located on Gallus gallus chromosomes (GGA) 1, 3, 4, 6, 11, and 12. The significant genomic regions were further investigated to examine if the genes within the regions were associated with the corresponding traits under heat stress. A candidate gene list including genes in the identified genomic regions that were also differentially expressed in chicken tissues under heat stress was generated. Understanding the correlation between genetic variants and resilience to heat stress is an important step towards improving heat tolerance in poultry.
... GSH is a low molecular weight thiolated tripeptide composed of glutamate, cysteine and glycine. [1] GSH plays a key role in signal transduction, apoptosis and gene expression and act as central redox agent in most aerobic organisms. GSH show antioxidant effect and is an important agent in scavenging free radicals triggering oxidative stress. ...
Glutathione (GSH), an oxidative stress biomarker plays a major role in different pathological processes and lead to a vast number of diseases including cancer. Biologically, cystine uptake is a fundamental factor in maintaining GSH levels in cells; however, the interaction between cystine and GSH in biological systems is least explored in developing sensors for GSH. In the present work, we have explored this interaction as the fundamental factor in “turn‐on” sensing of GSH from body fluids using a fluorescent gold nanocluster platform. The experimental results revealed that the probe displayed appreciable performance for GSH over a linear range from 0.2 mM to 1.3 mM with a limit of detection (LoD) of 0.43 μM. The probe also revealed sensitive as well as selective response towards GSH even in the presence of possible co‐existing interferants and provided satisfactory recovery percentage of 94.17 % to 108.12 % from real serum samples. These findings of the present study can be extended in future applications of sensing GSH from clinical samples.
