Explore chapters and articles related to this topic
Biochemical Methods of Studying Hepatotoxicity
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Prasada Rao S. Kodavanti, Harihara M. Mehendale
Glutathione (GSH) is a ubiquitous tripeptide, is present in large concentrations in the liver, and plays a major role in the elimination of a large number of nucleophilic exogenous toxicants. Thus, it is important in detoxification of several chemicals. Toxicant by itself could be nucleophilic or converted to nucleophiles by microsomal enzymes. During toxicity phase, GSH levels are drastically decreased and, most often, enzymes responsible in such processes are also affected. Glutathione metabolism is also important in quenching reactive intermediates and radical species generated by oxidative toxicity. The enzymes involved in the GSH-mediated removal of oxyradicals, and peroxides include GSH-peroxidase, catalase, and superoxide dismutase. The ultimate result of oxidative stress is the formation of glutathione disulfide (GSSG) at the expense of reducing equivalents like NADPH (Figure 2). GSSG-reductase is very necessary in maintaining cellular homeostasis of reduced GSH. This section is devoted to the methods usually employed to measure GSH, other thiols, disulfides, and related enzymes.
The Glutathione Redox State and Zinc Mobilization from Metallothionein and Other Proteins with Zinc–Sulfur Coordination Sites
Published in Christopher A. Shaw, Glutathione in the Nervous System, 2018
We have shown a different type of reactivity of the zinc–sulfur bond, namely, a reaction of the cysteines in MT with biological disulfides (Maret 1994b, 1995b). Glutathione disulfide interacts with MT and releases zinc in a monophasic reaction, indicating similar or equal reactivity of the two clusters in MT and a process in which an initial S-thiolation of critical cysteines leads to collapse of each cluster. This reaction provides a new mechanism for release of zinc from MT and could proceed by direct attack of the disulfide on the intact zinc–sulfur bond or in a reaction with the free thiol that dissociates from zinc. Because of the aforementioned activation of cysteine thiolate by zinc, we favor the first possibility and have termed this reaction zinc-thiol–disulfide interchange. Even though this interchange (glutathionylation) itself is not an oxidation, the formation of intra- and intermolecular disulfides in MT in the presence of excess disulfide reagent constitutes an oxidation of MT. It is also an oxidative process in the sense that a disulfide has to be generated for this type of metal release to occur.
Orthomolecular Parenteral Nutrition Therapy
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Arturo O'Byrne-Navia, Arturo O'Byrne-De Valdenebro
Although the concomitant use of vitamin C with GSH can be recommended in many pathological states, it has been discussed if this notion can be considered universal. Oncologic disease is one of the areas where this postulate has been put to debate. The Glutathione paradox in cancer has been exemplary described by Traverso and colleagues in their 2013 paper: “While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells” (Traverso et al. 2013). This poses interesting questionings about the role of GSH either as a potential treatment against cancer or as a cancer cell protector.
Comparative evaluation of the effects of bisphenol derivatives on oxidative stress parameters in HepG2 cells
Published in Drug and Chemical Toxicology, 2023
Busra Ozyurt, Gizem Ozkemahli, Anil Yirun, Aylin Balci Ozyurt, Merve Bacanli, Nursen Basaran, Belma Kocer-Gumusel, Pinar Erkekoglu
In our study, we determined that exposure to BPF and BPS significantly decreased GPx activity. In addition, BPA increased SOD activity vs. control although other bisphenol derivatives did not cause any changes. None of the bisphenol derivatives significantly altered CAT activity. Total GSH levels showed a significant increase in all bisphenol groups. As we measured total glutathione levels, we can only suggest that the reason for the increase in total GSH levels may be an adaptive response to the short-term bisphenol application. In addition, there may also be a significant increase in glutathione disulfide (GSSG) levels. While MDA levels did not increase in the bisphenol-exposed HepG2 cells, significant increases in protein oxidation were determined in the BPF and BPS groups. In this case, we can assume that bisphenol derivatives can induce protein oxidation independently of lipid peroxidation in HepG2 cells after 24 h of application.
Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome
Published in Gut Microbes, 2021
Clara Depommier, Amandine Everard, Céline Druart, Dominique Maiter, Jean-Paul Thissen, Audrey Loumaye, Michel P. Hermans, Nathalie M. Delzenne, Willem M. de Vos, Patrice D. Cani
Compared to the placebo group, a total of 54 and 41 metabolites were identified as specifically and significantly modified following 3 months of supplementation with alive or pasteurized A. muciniphila, respectively. Briefly, 9 metabolites increased and 32 decreased in the pasteurized group, while 11 increased and 43 decreased in the alive group. The list of metabolites, with details of the corresponding pathways, is provided in Supplementary Tables 1 and 2. Of note, several metabolites related to the oxidative state were modulated. Cysteinylglycine (cys-gly) and oxidized cys-gly, two glutathione cycle intermediates, were significantly decreased by the alive from compared to the placebo group. Moreover, plasma levels of cysteine glutathione disulfide were significantly reduced in the alive group compared to baseline value (matched paired t-test, pv = 0.04). Global screening reveals differential modulation of the circulating metabolome between both treatment groups, with distinct signatures according to the form administrated. Nevertheless, it is worth underlining that alanine, arginine, caproate, 1-carboxyethylphenylalanine, and 3-hydroxyhexanoylcarnitine are among the metabolites that were altered in the same way regardless of the form administered. In conclusion, untargeted metabolomic profiling reveals both shared and distinct effects of alive and pasteurized forms on the serum metabolome in individuals with excess body weight and insulin resistance.
Methylcyclopentadienyl manganese tricarbonyl increases cell vulnerability to oxidative stress on rat thymocytes
Published in Drug and Chemical Toxicology, 2019
In addition, 10 µM and 30 µM MMT significantly decreased the intensity of 5-CMF, but the treatment with 100 µM MMT did not change the intensity of 5-CMF. Glutathione can be regenerated from glutathione disulfide by the enzyme glutathione reductase, which is activated by oxidative stress (Deponte 2013). Therefore, temporary activation of glutathione reductase by 100 µM MMT may increase the intensity of 5-CMF fluorescence. We have shown that the treatment with MMT on rat thymocytes increases cell vulnerability to oxidative stress. Hakkinen and Haschek (1982) reported that administration by intraperitoneal injection of MMT (5 mg/kg) resulted in lung cell damage in rats. In addition, MMT at 100 µM induces toxic effect in neural cells (Kitazawa et al.2002, Anantharam et al.2004, Su et al.2017). Therefore, MMT at over 30 µM induces the toxic effect in all cells.