Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury
Methylmercury (MeHg) toxicity may vary widely despite similar levels of exposure. This is hypothetically related to genetic differences in enzymes metabolizing MeHg. MeHg causes oxidative stress in experimental models but little is known about its effects on humans. The aims of the present study was to evaluate the effects of polymorphisms in glutathione (GSH)-related genes (GSTM1, GSTT1, GSTP1 and GCLM) on Hg concentrations in blood and hair, as well as MeHg-related effects on catalase (CAT) and glutathione-peroxidase (GPx) activity and GSH concentrations. Study subjects were from an Amazonian population in Brazil chronically exposed to MeHg from fish. Hg in blood and hair were determined by ICP-MS, CAT, GPx and GSH were determined by spectrophotometry, and multiplex PCR (GSTM1 and GSTT1) and TaqMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48±36 μg/L and 14±10 μg/g. Persons with the GCLM-588 TT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood β=-0.32, p=0.017; and hair β=-0.33; p=0.0090; adjusted for fish intake, age and gender). GSTM1*0 homozygous had higher blood (β=0.20; p=0.017) and hair Hg (hair β=0.20; p=0.013). Exposure to MeHg altered antioxidant status (CAT: β=-0.086; GSH: β=-0.12; GPx: β=-0.16; all p<0.010; adjusted for gender, age and smoking). Persons with GSTM1*0 had higher CAT activity in the blood than those with GSTM1. Our data thus indicate that some GSH-related polymorphisms, such as GSTM1 and GCLM may modify MeHg metabolism and Hg-related antioxidant effects.
The effects of Nigella sativa seeds and thymoquinone on aflatoxin phase-2 detoxification through glutathione and glutathione-S-transferase alpha-3, and the relationship between aflatoxin B1-DNA adducts in broilers
The primary pathway of the detoxification of aflatoxin (AF) metabolites occurring at the end of phase-1 biotransformation is glutathione (GSH) conjugation via glutathione-S-transferase (GST) enzyme in phase-2. In this study, the activity of Nigella sativa seeds (NS) and thymoquinone (TQ) on phase-2 detoxification pathways of AF was investigated in light of GSH, GST alpha-3 (GSTA3), and AFB1-DNA adducts detected by the immunohistochemical method in broilers' livers. One-hundred twenty chickens at one-day-old were divided into six groups as the control (CNT), AF, TQ, NS, AF + TQ, and AF + NS groups and fed for 28 days. AF, TQ, and NS were added to the relevant diets at 2 mg/kg, 300 mg/kg, and 5%, respectively. The administration of AF alone strongly stimulated the formation of AFB1-DNA adduct and reduced GSH and GSTA3 levels in hepatocytes (p < 0,01). In contrast, TQ and NS were found to reduce significantly the amount of AFB1-DNA adducts in AF + TQ and AF + NS groups (p < 0,01). We concluded that NS and TQ achieved this by increasing GSH and GSTA3 levels (p < 0,01) thanks to their antioxidant properties, and hence detoxifying the reactive metabolites of AF. Also, we consider that the AFB1-DNA adduct constituted in 28 days can be used as a biomarker for exposure to AF in broilers.
