Glutathione Transferase

Fluorochloridone (FLC) is a herbicide used worldwide that is thought to be safe. However, due to its potential genotoxicity, cytotoxicity, and even systematic toxicity, there are increasing concerns about human exposure to this compound. Thus, the metabolism and bioactivation of FLC was investigated. After oral administration to mice, 27 metabolites were identified by ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry and with further structural identification by nuclear magnetic resonance spectroscopy. Hydroxylation and oxidative dechlorination were the major phase I pathways, while glutathione (GSH) and N-acetylcysteine conjugations were two major phase II pathways, indicating the formation of a reactive intermediate. In vitro microsomal and cytosolic studies revealed that a GSH conjugate (M13) was the predominant metabolite of FLC formed through a nucleophilic SN2 substitution of 3-Cl by GSH; this pathway is NADPH indep...

Under laboratory conditions, the effects of thiamethoxam were investigated in larvae, pupae and emerging honey bees after exposure at larval stages with different concentrations in the food (0.00001 ng/μL, 0.001 ng/μL and 1.44 ng/μL). Thiamethoxam reduced the survival of larvae and pupae and consequently decreased the percentage of emerging honey bees. Thiamethoxam induced important physiological disturbances. It increased acetylcholinesterase (AChE) activity at all developmental stages and increased glutathione-S-transferase (GST) and carboxylesterase para (CaEp) activities at the pupal stages. For midgut alkaline phosphatase (ALP), no activity was detected in pupae stages, and no effect was observed in larvae and emerging bees. We assume that the effects of thiamethoxam on the survival, emergence and physiology of honey bees may affect the development of the colony. These results showed that attention should be paid to the exposure to pesticides during the developmental stages of ...

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens and genetic polymorphisms of CYP2E1 and GSTP1 genes have been studied extensively to evaluate the relative risk of various cancers. In the present study, we examined associations with CYP2E1 and GSTP1 gene polymorphisms in sporadic bladder cancers from North Indian patients. The subjects were 106 bladder cancer (Ca-B) cases and 162 age-matched controls. The GSTP1 313 A/G polymorphism was determined by the PCR/RFLP method using peripheral blood DNA. Binary Logistic Regression Model was used for assessing differences in genotype prevalence and their associations between patient and the control group. We observed a non-significant association in Pst1 polymorphism of the CYP2E1 gene; though the A/G genotype (OR = 2.69, 95% CI=1.57- 4.59, P= 0.000) and G/G genotype (OR = 7.68, 95% CI=2.77- 21.26, P= 0.000) of the GSTP1 gene polymorphism alone or in combination with to...

Recent attention is focused on understanding the genetic basis for individual susceptibility to the development of chronic disease. An emphasis is concentrated on establishing an association be-tween inheritance of polymorphic chemical metab-olizing genes and development of ...

DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correl...

Alcohol clamping is a technique that maintains a constant breath alcohol Concentration (BrAC) for prolonged intervals, thereby reducing experimental variance in the timc course of organ exposure to alcohol, when compared with oral alcohol administration paradigms. ...

GSTM1, T1 and P1 are important enzymes of glutathione S-transferases (GSTs), involved in the metabolism of many endogenous and exogenous compounds. Individual genetic variation in these metabolizing enzymes may influence the metabolism of their substrates. The present study was designed to determine the genotoxic effects using DNA damage and its association with GSTM1, GSTT1, and GSTP1 (Ile105Val) genetic polymorphisms in workers occupationally exposed to organophosphate pesticides (OPs). We examined 230 subjects including 115 workers occupationally exposed to OPs and an equal number of normal healthy controls. The DNA damage was evaluated using the alkaline comet assay and genotyping was done using individual PCR or PCR–RFLP. Significantly higher DNA tail moment (TM) was observed in workers as compared to control subjects (14.41 ± 2.25 vs. 6.36 ± 1.41 tail % DNA, p < 0.001). The results revealed significantly higher DNA TM in workers with GSTM1 null genotype than those with GSTM1 positive (15.18 vs. 14.15 tail % DNA, p = 0.03). A significantly higher DNA TM was also observed in workers with homozygous Ile–Ile GSTP1 genotype than heterozygous (Ile–Val) and mutant (Val–Val) GSTP1 genotype (p = 0.02). In conclusion, the results show that null deletion of GSTM1 and homozygote wild GSTP1 genotype could be related to inter-individual differences in DNA damage arises from the gene–environment interactions in workers occupationally exposed to OPs.• DNA damage and its association with GSTM1, GSTT1 and GSTP1 genotypes carried out. • Workers with exposure to organophosphate pesticides found increased DNA damage. • DNA damage observed to be associated with GSTM1 null and GSTP1 Ile/Ile genotypes.

Oxidative stress is involved in the pathophysiology of diabetes mellitus. In the present study, 68 patients with type 2 diabetes mellitus and 31 clinically healthy individuals were evaluated. The patients were divided into two groups. Group 1 included 29 patients without diabetic complications and group 2 consisted of 39 patients with diabetic complications. Erythrocyte glutathione, superoxide dismutase, and thiobarbituric acid-reactive substance levels as well as plasma antioxidant vitamins C and E, and serum total glutathione-S-transferase, ceruloplasmin, and protein thiols were estimated by using spectro-photometer. A significant decrease of erythrocyte glutathione was observed in group 1 when compared with the controls. Thiols decreased in group 2. An increase in glutathione-S-transferase, ceruloplasmin, superoxide dismutase, and vitamins C and E levels was noted in patients with diabetes mellitus. Thiobarbituric acid-reactive substance levels decreased in group 1 but increased ...

In addition to forming bilayers to separate cellular compartments, lipids participate in vesicular trafficking and signal transduction. Among others, phosphatidic acid (PA) is emerging as an important signaling molecule. The spatiotemporal distribution of cellular PA appears to be tightly regulated by localized synthesis and a rapid metabolism. Although PA has been long proposed as a pleiotropic bioactive lipid, when and where PA is produced in the living cells have only recently been explored using biosensors that specifically bind to PA. The probes that we have generated are composed of the PA-binding domains of either Spo20p or Raf1 directly fused to GFP. In this chapter, we will describe the expression and purification of GST-fusion proteins of these probes, and the use of phospholipid strips to validate the specificity of their interaction with PA. We will then illustrate the use of GFP-tagged probes to visualize the synthesis of PA in the neurosecretory PC12 cells and RAW 267....

In order to mimic the biological effects of an oil spill in Arctic waters, we examined several types of biomarkers (genes, enzymes, metabolites, and DNA damage) in polar cod Boreogadus saida experimentally exposed to the water soluble fractions of crude oil. During 4 weeks of ...

In the postgenomic era, the analytical challenges associated with deciphering the structure–function relationship of complex oligosaccharides have resulted in the development of high-throughput technologies that are well suited for glycomic analysis. 1, 2 Lectin microarrays ...

Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p&lt;0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved redu...

In the present work, we investigated the potential use of several antioxidant enzymes in wild mussels (Mytilus galloprovincialis) as biomarkers of marine pollution. The enzymatic activity levels of glutathione S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) were measured in gills and digestive gland. Those enzymes participate in the cellular defense system that is involved in the adaptive response of organisms to chemical pollution. Adult mussels were collected at five sampling sites located at the Ría de Pontevedra and Ría de Vigo. Seasonal variations in the control site were observed for the CAT activity, but no significant variability was found for GST and GPx. Mussels from the most polluted sites exhibited a significantly greater GST activity compared to the control site (p&lt;0.05) during the sampling period, whereas GPx and CAT activities have not such a marked pattern. Trace metals, PAHs, PCBs and DDT contents in mussels at sampling sites showed highly si...

h i g h l i g h t s We evaluated the toxicity of yperite to fish through in vivo and field studies. Fish resulted sensitive targets of yperite toxic effects. In vivo yperite induces EROD and UGT activities and histological alterations. The field study showed multiple detrimental effects in fish from the dumping area. a r t i c l e i n f o a b s t r a c t The aim of this study was to evaluate the potential toxicological effects on fish related to the leakage of yperite from rusted bomb shells dumped at sea. Both in vivo and field studies have been performed. As for the in vivo experiment, specimen of European eel were subcutaneously injected with 0.015, 0.15 and 1.5 mg/kg of yperite and sacrificed after 24 and 48 h. In the field study, specimen of Conger eel were collected from a dumping site in the Southern Adriatic Sea. The presence/absence of yperite in tissues, genotoxicity, detoxification enzymes, histological alterations and gross abnormalities were investigated. Results of the...