Polymorphisms in glutathione-related genes modify mercury concentrations and antioxidant status in subjects environmentally exposed to methylmercury

Autor(es):Mostrar menos -

Mazzaron Barcelos, Gustavo Rafael ^[1] ; Grotto, Denise ^[1] ; de Marco, Katia Cristina ^[1] ; Valentini, Juliana ^[1] ; Lengert, Andre van Helvoort ^[2] ; Soares de Oliveira, Andreia Avila ^[1] ; Garcia, Solange Cristina ^[3] ; Leite Braga, Gilberto Ubida ^[1] ; Engstrom, Karin Schlawicke ^[4] ; de Syllos Colus, Ilce Mara ^[2] ; Broberg, Karin ^[4] ; Barbosa, Jr., Fernando ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, BR-14040903 Sao Paulo - Brazil

^[2] Univ Estadual Londrina, Ctr Biol Sci, Dept Gen Biol, BR-86051990 Londrina, Parana - Brazil

^[3] Univ Fed Rio Grande do Sul, Sch Pharm, BR-96610000 Porto Alegre, RS - Brazil

^[4] Univ Lund Hosp, Div Occupat & Environm Med, S-22185 Lund - Sweden

• Tipo de documento: Artigo Científico
• Fonte: Science of The Total Environment; v. 463, p. 319-325, OCT 1 2013.
• Citações Web of Science: 36

Resumo

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 TagMan assays (GSTP1 and GCLM) were used for genotyping. Mean Hg concentrations in blood and hair were 48 +/- 36 mu g/L and 14 +/- 10 mu g/g. Persons with the GCLM-588 IT genotype had lower blood and hair Hg than did C-allele carriers (linear regression for Hg in blood beta = -0.32, p = 0.017; and hair beta = -0.33; p = 0.0090; adjusted for fish intake, age and gender). GSTM1{*}0 homozygous had higher blood (beta = 0.20; p = 0.017) and hair Hg (hair beta = 0.20; p = 0.013). Exposure to MeHg altered antioxidant status (CAT:beta = -0.086; GSH:beta = -0.12; GPx:beta = -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. (C) 2013 Elsevier BY. All rights reserved. (AU)

• Processo FAPESP: 11/22575-0 - Avaliação da influência de polimorfismos de genes relacionados à glutationa sobre as concentrações de mercúrio em indivíduos ambientalmente expostos ao metal, em comunidades ribeirinhas na região do rio Tapajós, Pará
• Beneficiário: Gustavo Rafael Mazzaron Barcelos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 10/16691-4 - Avaliação de polimorfismos genéticos relacionados ao metabolismo e toxicidade do mercúrio e chumbo em comunidades ribeirinhas expostas aos metais, na região amazônica
• Beneficiário: Gustavo Rafael Mazzaron Barcelos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado