Evaluation of toxic effects of a diet containing fish contaminated with methylmercury in rats mimicking the exposure in the Amazon riverside population Denise Grotto a , Juliana Valentini a , Juliana Mara Serpeloni a , Patrı ´cia Alves Ponte Monteiro b , Elder Francisco Latorraca c , Ricardo Santos de Oliveira c , Lusˆ ania Maria Greggi Antunes a , Solange Cristina Garcia d , Fernando Barbosa Jr a,n a Departamento de Ana ´lises Clı ´nicas, Toxicolo ´gicas e Bromatolo ´gicas, Faculdade de Ciˆ encias Farmacˆ euticas de Ribeir ~ ao Preto, Universidade de S ~ ao Paulo, 14040-903 Ribeir ~ aoPreto, S ~ ao Paulo, Brazil b Departamento de Patologia, Faculdade de Medicina de Ribeir ~ ao Preto, Universidade de S ~ ao Paulo, Brazil c Departamento de Cirurgia E Anatomia, Faculdade de Medicina de Ribeir ~ ao Preto, Universidade de S ~ ao Paulo, Brazil d Departamento de Ana ´lises Clı ´nicas, Universidade Federal do Rio Grande do Sul, Brazil article info Article history: Received 13 May 2011 Received in revised form 14 September 2011 Accepted 21 September 2011 Available online 13 October 2011 Keywords: Fish consumption Methylmercury Oxidative stress Genotoxicity Inflammation Blood pressure abstract This study was designed to evaluate the effects of a diet rich in fish contaminated with MeHg, mimicking the typical diet of the Amazon riverside population, in rats. Animals were randomly assigned to one of three groups with eight rats in each group: Group Icontrol, received commercial ration; Group IIreceived a diet rich in uncontaminated fish; Group IIIreceived a diet rich in fish contaminated with MeHg. Treatment time was 12 weeks. Oxidative stress markers were evaluated, as well as the effects of this diet on DNA stability, systolic blood pressure (SBP), nitric oxide (NO) levels and histological damage in different tissues. There was a significant increase in SBP values in rats fed with MeHg-contaminated fish diet after the 10th week of the treatment. As far as oxidative stress biomarkers are concerned, no differences were observed in reduced glutathione and protein carbonyl levels, glutathione peroxidase, catalase, superoxide dismutase or d-aminolevulinate dehydratase activities between the groups of animals receiving contaminated and uncontaminated fish diets. On the other hand, malondialdehyde levels increased significantly in rats fed with contaminated fish. NO levels were similar in all groups. DNA migration showed augmented in rats exposed to contaminated fish and histopathological analyses showed weak but significant leukocyte infiltration. Thus, we conclude that the MeHg-contaminated fish diet induced a slight lipid peroxidation and genotoxicity. However, these effects seem to be much less pronounced than when rats are exposed to aqueous solution containing CH 3 HgCl. Our findings support the contention that the chemical form of MeHg in fish or fish nutrients such as polyunsaturated fatty acids, Se or vitamin E could minimize the toxic effects of MeHg exposure in fish- eating communities. & 2011 Elsevier Inc. All rights reserved. 1. Introduction Mercury (Hg) is one of the most toxic pollutants, methylmer- cury (MeHg) being the most toxic forms of Hg. Its toxicity is particularly linked to the nervous system, involving disturbances of sensation in the extremities, ataxia, constriction of the visual field and muscular weakness (WHO, 1996). Renal, immunological and cardiovascular effects after MeHg exposure have also been demonstrated (Augusti et al., 2008; Clarkson, 2002; Fillion et al., 2006; Silbergeld et al., 2005; Virtanen et al., 2007). Fish or seafood consumption is an important route for human MeHg exposure (Clarkson and Magos, 2006; Malm et al., 1995). In the Amazon Basin, fish contaminated with Hg have been recognized as a problem affecting riparian people, whose main source of protein is fish. Many studies have shown a strong correlation between fish consumption and Hg exposure in these populations (Cordier et al., 2002; Dolbec et al., 2000; Dorea et al., 2003; Pinheiro et al., 2008). Despite the pronounced high expo- sure to MeHg, little is known about possible toxic effects. In an epidemiologic study with adults living in a village along the Tapajo ´ s River, Brazil, a decrease in near visual contrast sensitivity Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/envres Environmental Research 0013-9351/$ - see front matter & 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2011.09.013 n Corresponding author. Fax: þ55 16 36024725. E-mail address: fbarbosa@fcfrp.usp.br (F. Barbosa Jr). Environmental Research 111 (2011) 1074–1082