Effects of genetic polymorphisms on antioxidant status and concentrations of the metals in the blood of riverside Amazonian communities co-exposed to Hg and Pb.
There have been reports of genetic effects affecting the metabolism of Hg and Pb individually, and thus modulating their toxicities. However, there is still a knowledge gap with respect to how genetics may influence the toxicities of these toxic metals during a co-exposure scenario. This present study is therefore aimed at investigating the effects of polymorphisms in genes (GSTM1, GSTT1, GSTP1, GCLM, GCLC, GPx1, ALAD, VDR and MDR1) that have been implicated in Hg and Pb metabolisms affects the kinetics of these metals, as well as various blood antioxidant status parameters: MDA and GSH, and the activities of CAT, GPx and ALAD among populations that have been co-exposed to both Hg and Pb. Study subjects (207 men; 188 women) were from an Amazonian population in Brazil, exposed to Hg and Pb from diet. The blood levels of Hg and Pb were determined by ICP-MS while genotyping were performed by PCR assays. The median values of Hg and Pb in blood were 39.8µg/L and 11.0µg/dL, respectively. GSTM1, ALAD and VDR polymorphisms influenced Hg in blood (β=0.17; 0.37 and 0.17; respectively, p<0.050) while variations on GCLM, GSTT1 and MDR1 (TT) modulated the concentrations of Pb among the subjects (β=-0.14; 0.13 and -0.22; re-spectively, p<0.050). GSTT1 and GCLM polymorphisms also are associated to changes of MDA concentrations. Persons with null GSTM1 genotype had higher activity of the antioxidant enzyme CAT than carries of the allele. Individuals with deletion of both GSTM1 and GSTT1 had a decreased expression of GPx compared to those that expressed at least, one of the enzymes. ALAD 1/2 subjects had lower ALAD activity than individuals with the non-variant genotype. Our findings give further support that polymorphisms related to Hg and Pb metabolism may modulate Hg and Pb body burden and, consequently metals-induced toxicity.
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903 Ribeirão Preto, SP, Brazil. Electronic address: barcelos@fcfrp.usp.br.
Gustavo Rafael Mazzaron
GR
Barcelos
Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990 Londrina, PR, Brazil.
Marilesia Ferreira de
MF
Souza
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903 Ribeirão Preto, SP, Brazil.
Andréia Ávila Soares de
AÁ
Oliveira
Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990 Londrina, PR, Brazil.
André van Helvoort
Av
Lengert
Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990 Londrina, PR, Brazil.
Marcelo Tempesta de
MT
Oliveira
Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990 Londrina, PR, Brazil.
Rossana Batista de Oliveira Godoy
RB
Camargo
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903 Ribeirão Preto, SP, Brazil.
Denise
D
Grotto
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903 Ribeirão Preto, SP, Brazil.
Juliana
J
Valentini
School of Pharmacy, Federal University of Rio Grande do Sul, Avenida Ipiranga, 2752, CEP 90610-000, Porto Alegre, RS, Brazil.
Solange Cristina
SC
Garcia
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903 Ribeirão Preto, SP, Brazil.
Gilberto Úbida Leite
GÚ
Braga
Department of General Biology, Center for Biological Sciences, State University of Londrina, Rodovia Celso Garcia Cid km 380, CEP 86051-990 Londrina, PR, Brazil.
Ilce Mara de Syllos
IM
Cólus
Department of Biological Sciences, Faculty of Basic and Applied Sciences, Osun State University, P.M.B. 4494 Osogbo, Osun State, Nigeria.
Joseph
J
Adeyemi
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, CEP 14040-903 Ribeirão Preto, SP, Brazil.
Fernando
F
Barbosa
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism*; D001938:Brazil; D003430:Cross-Sectional Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008767:Methylmercury Compounds / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
D000975:Antioxidants; D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D007854:Lead
Antioxidant parameters; Lead; Mercury; Metabolism; Polymorphisms