scholarly journals Overexpression of Erythrocyte Glutathione S-Transferase in Uremia and Dialysis

1999 ◽  
Vol 45 (10) ◽  
pp. 1781-1788 ◽  
Author(s):  
Francesco Galli ◽  
Simona Rovidati ◽  
Serena Benedetti ◽  
Umberto Buoncristiani ◽  
Carla Covarelli ◽  
...  

Abstract Background: Overexpression of glutathione S-transferase (GST; EC 2.5.1.18) has been documented in the erythrocytes of patients with chronic renal failure, and this event may well be of relevance from a clinical standpoint. In fact, it could serve as a marker of uremic toxicity overall, which can contribute to impair the function and survival of the erythrocytes. However, the biochemical details of this phenomenon are poorly understood. Methods: In this study, we characterized the expression of GST in erythrocytes of 118 uremic patients under different clinical conditions. The mechanisms responsible for the regulation of protein expression and enzyme activity were investigated in light of different dialysis approaches, oxidative stress, uremic toxins, erythrocyte age, and erythropoietin (EPO) supplementation. Results: Mean GST activity in uremic patients was highly overexpressed with respect to controls, and this phenomenon was exclusively attributable to an increased expression of GST. Overexpression of GST did not appear to be dependent on oxidative stress and was not influenced by vitamin E supplementation. In the same manner, both erythrocyte age and EPO supplementation apparently did not interfere with the GST concentrations, which were the same in controls and patients. Preliminary experiments suggested that high-molecular weight or protein-bound toxins could play some role in the overexpression of GST. Conclusions: GST expression may be a useful marker for the individual accumulation of uremic toxins as well as of the efficiency of new dialysis strategies in removing them.

2020 ◽  
Vol 17 (3) ◽  
pp. 191-199
Author(s):  
Seval Yilmaz ◽  
Fatih Mehmet Kandemir ◽  
Emre Kaya ◽  
Mustafa Ozkaraca

Objective: This study aimed to detect hepatic oxidative damage caused by aflatoxin B1 (AFB1), as well as to examine how propolis protects against hepatotoxic effects of AFB1. Method: Rats were split into four groups as control group, AFB1 group, propolis group, AFB1+ propolis group. Results: There was significant increase in malondialdehyde (MDA) level and tumor suppressor protein (TP53) gene expression, Glutathione (GSH) level, Catalase (CAT) activity, CAT gene expression decreased in AFB1 group in blood. MDA level and Glutathione-S-Transferase (GST) activity, GST and TP53 gene expressions increased in AFB1 group, whereas GSH level and CAT activity alongside CAT gene expression decreased in liver. AFB1+propolis group showed significant decrease in MDA level, GST activity, TP53 and GST gene expressions, GSH level and CAT activity and CAT gene expression increased in liver compared to AFB1 group. Conclusion: These results suggest that propolis may potentially be natural agent that prevents AFB1- induced oxidative stress and hepatotoxicity.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jobaida Akther ◽  
Akio Ebihara ◽  
Tsutomu Nakagawa ◽  
Laila N. Islam ◽  
Fumiaki Suzuki ◽  
...  

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/−), 31.4% had GSTT1 (−/+) alleles, and 6.4% had null genotypes (−/−) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/−, 30.5% were −/+, and 8.4% were −/−. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes.


Medicina ◽  
2020 ◽  
Vol 56 (2) ◽  
pp. 70 ◽  
Author(s):  
Janina Didžiapetrienė ◽  
Birutė Kazbarienė ◽  
Renatas Tikuišis ◽  
Audrius Dulskas ◽  
Daiva Dabkevičienė ◽  
...  

Background and Objectives: The purpose of this study is to evaluate the level of oxidative stress before and after breast cancer surgery. Materials and Methods: Malondialdehyde (MDA) level was tested using a thiobarbituric acid (TBA) assay based on the release of a color complex due to TBA reaction with MDA. The glutathione S-transferase (GST) activity was evaluated by enzymatic conjugation of reduced glutathione (GSH) with 1-chloro-2,4-dinitrobenzene. The level of total glutathione (reduced GSH and oxidized GSSG) was detected using a recycling system by 5,5-dithiobis(2-nitrobenzoic acid). The levels of the indices were determined in the serum of 52 patients before surgery, two hours and five days after surgery, and in 42 healthy women. Results: In the patients over 50 years old the level of MDA was higher after surgery in comparison with before surgery, and GST activity was lower in comparison with the control. The GSH + GSSG level in both ages groups after surgery was lower than in the control. Significant differences of MDA level were detected in patients with stage III after surgery compared to the control. The level of GSH + GSSG was significantly lower in the patients with I–III stages compared to the control. Conclusion: The most expressed changes demonstrate the significance of MDA as a marker to evaluate oxidative stress in breast cancer patients. The degree of oxidative stress depends on the patient’s age and stage of disease. (1) Malondialdehyde can be used as an oxidative stress marker; (2) A higher stage of the disease and older age correspond to a higher rise of malondialdehyde, suggesting more intensive oxidative stress.


2021 ◽  
Vol 55 (5) ◽  
pp. 635-650

BACKGROUND/AIMS: Renal ischemia and reperfusion injury (IRI) involves oxidative stress, disruption of microvasculature due to endothelial cell damage, loss of epithelial cell polarity secondary to cytoskeletal alterations, inflammation, and the subsequent transition into a mesenchymal phenotype. Ischemic preconditioning (IPC) has been proposed as a therapeutic strategy to avoid/ameliorate the IRI. Since previous results showed that IPC could have differential effects in kidney cortex vs. kidney medulla, in the present study we analyzed the effectiveness and molecular mechanisms implicated in IPC in both kidney regions. METHODS: We evaluated 3 experimental groups of BALB/c male mice: control (sham surgery); renal ischemia (30 min) by bilateral occlusion of the renal pedicle and reperfusion (48 hours) (I/R); and renal IPC (two cycles of 5 min of ischemia and 5 min of reperfusion) applied just before I/R. Acute kidney injury was evaluated by glomerular filtration rate (GFR), Neutrophil Gelatinase-Associated Lipocalin (NGAL) blood level, and histologic analysis. Oxidative stress was studied measurement the Glutathione S-Transferase (GST) activity, GSH/GSSG ratio, and lipoperoxidation levels. Inflammatory mediators (IL-1β, IL-6, Foxp3, and IL-10) were quantified by qRT-PCR. The endothelial (PECAM-1), epithelial (AQP-1), mesenchymal (Vimentin, Fascin, and Hsp47), iNOS, clusterin, and Hsp27 expression were evaluated (qRT-PCR and/or Western blot). RESULTS: The IPC protocol prevented the decrease of GFR, reduced the plasma NGAL, and ameliorated morphological damage in the kidney cortex after I/R. The IPC also prevented the downregulation of GST activity, lipoperoxidation and ameliorated the oxidized glutathione. In addition, IPC prevented the upregulation of vimentin, fascin, and Hsp47, which was associated with the prevention of the downregulation of AQP1 after I/R. The protective effect of IPC was associated with the upregulation of Hsp27, Foxp3, and IL-10 expression in the renal cortex. However, the upregulation of iNOS, IL-1β, IL-6, and clusterin by I/R were not modified by IPC. CONCLUSION: IPC conferred better protection in the kidney cortex as compared to the kidney medulla. The protective effect of IPC was associated with amelioration of oxidative stress, tubular damage, and the induction of markers of Treg lymphocytes activity in the cortical region. Further studies are needed to evaluate if lower tubular cell stress/damage after I/R may explain the preferential induction of Treg response in the kidney cortex induced by IPC.


1998 ◽  
Vol 26 (3) ◽  
pp. 321-330 ◽  
Author(s):  
Concepción García-Alfonso ◽  
Guillermo Repetto ◽  
Pilar Sanz ◽  
Manuel Repetto ◽  
Juan López-Barea

The enzymes glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G-6PDH) are implicated in the defence against oxidative stress. GST is mainly involved in the conjugation of electrophilic compounds with glutathione (GSH), although some of its isoenzymes display peroxidase activity. G-6PDH and glutathione reductase regenerate NADPH and GSH, respectively, to restore the reduced intracellular redox status following oxidative stress. Enzymatic assays for GST and G-6PDH were adapted and optimised to permit the direct in vitro determination of the effects of toxicants which induce oxidative stress in cells on microtitre plates, thereby avoiding the need to prepare cell-free extracts. To optimise the conditions of the enzymatic assays, GST activity’ was measured at substrate concentrations of 1–3mM GSH and 1–3mM 1-chloro-2,4-dinitrobenzene, while G-6PDH activity was measured at 7.5–37.5mM glucose-6-phosphate and 55–275mM NADP. Both enzymatic activities were directly proportional to cell number up to a density of 1 x 105 cells/well. The effects on GST and G-6PDH activities of three toxicants which induce oxidative stress — paraquat, iron (II) chloride and iron (III) chloride — were compared in cultured Vero cells to validate the new assays. Specific GST activity increased to 145% and 171% compared to the controls in cells treated with 5mM paraquat and 5mM iron (II) chloride, respectively, but was inhibited after exposure to 25mM iron (III) chloride. Specific G-6PDH activity increased to 136% compared to the control after exposure to 5mM paraquat, but was inhibited in cells exposed to 5mM iron (II) chloride and 25mM iron (III) chloride.


2014 ◽  
Vol 7 (3) ◽  
pp. 134-138
Author(s):  
Miroslav Pohanka

ABSTRACT Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), ferric reducing antioxidant power (FRAP), caspase-3 and activity of acetylcholinesterase (AChE) were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed.


2019 ◽  
Vol 17 (4) ◽  
Author(s):  
Carlos Eduardo Copatti ◽  
Bernardo Baldisserotto ◽  
Carine de Freitas Souza ◽  
José María Monserrat ◽  
Luciano Garcia

ABSTRACT This study aimed to assess the effects of low and high water hardness in interaction with different water pH in pacu (Piaractus mesopotamicus). Pacu juveniles were subjected to low (50 mg CaCO3 L-1 - LWH) or high water hardness (120 mg CaCO3 L-1 - HWH) at water pH of 5.5 (acidic), 7.5 (circumneutral) or 9.0 (alkaline) for 15 days. Gills and kidneys were collected (days 1, 5 and 15). Gill Na+/K+-ATPase (NKA) and vacuolar-type H+-ATPase (V-ATPase) activities were higher in alkaline pH with HWH on day 1. Gill and kidney NKA and V-ATPase activities were higher in acidic pH with LWH on day 15. Gill NKA activity of pacus under alkaline pH with LWH was higher than those exposed to HWH. Reduced antioxidant capacity in the gills and kidney and enhanced thiobarbituric acid reactive substances (TBARS) levels were demonstrated in fish exposed to acidic or alkaline pH, mainly with LWH. HWH increased glutathione-S-transferase (GST) activity and reduced TBARS levels in the gills and kidney. On day 15, GST activity was increased at acidic pH with LWH. In conclusion, circumneutral pH presents less oxidative stress and fewer variations in ATPases and HWH reduced deleterious effects in fish exposed to acidic or alkaline pH.


2019 ◽  
Vol 12 (3) ◽  
pp. 293-305
Author(s):  
N.S. Souto ◽  
M. Dassi ◽  
A.C.M. Braga ◽  
E.V.F. Rosa ◽  
M.R. Fighera ◽  
...  

Food products are susceptible to contamination by mycotoxins, and aflatoxin B1 (AFB1) stands as the most toxic among them. AFB1 intoxication results in distinct signs, including widespread systemic toxicity. Aspartame (ASP) is an artificial sweetener used as a sugar substitute in many products, and compelling evidence indicates ASP can be toxic. Interestingly, mechanisms underlying ASP and AFB1 toxicity involve oxidative stress. In this context, concomitant use of ASP and AFB1 in a meal may predispose to currently unidentified behavioural and biochemical changes. Therefore, we evaluated the effect of AFB1 (250 μg/kg, intragastrically (i.g.)) and/or ASP (75 mg/kg, i.g.) exposure for 7 days on behavioural and biochemical markers of oxidative stress in male Wistar rats. AFB1 and/or ASP increased hepatic glutathione S-transferase (GST) activity when compared to controls. In the kidneys, increased GST activity was detected in AFB1 and AFB1+ASP groups. In addition, AFB1 and or ASP elicited behavioural changes in the open field, marble burying and splash tests, however no additive effects were detected. Altogether, present data suggest AFB1 and ASP predispose to anxiety- and obsessive-compulsive-like symptoms, as well as to enzymatic defence system imbalance in liver and kidney of Wistar rats.


2016 ◽  
pp. 45-49
Author(s):  
P.N. Veropotvelyan ◽  
◽  
I.S. Tsehmistrenko ◽  
N.P. Veropotvelyan ◽  
N.S. Rusak ◽  
...  

Was to conduct a systematic review of data on the relationship between polymorphisms genes of detoxification system and development of preeclampsia (РЕ). Рresents the main genes of detoxification system (GSTPI, GSTМI, GSTТI, GРХI, ЕРНХI, SOD-2, SOD-3, CYPIAL, MTHЕR, MTR) and their functions. Of interest is the possibility of calculating the individual risk of PE based on the results about the presence of a combination of different polymorphisms in the genotype of the female. Question about early diagnosis of РЕ remains controversial and not fully understood. It is necessary to conduct further in-depth, extended study of this problem. Key words: preeclampsia, oxidative stress, genes of the detoxification system.


Sign in / Sign up

Export Citation Format

Share Document