Evaluation of toxic effects of chronic exposure at low doses of lead and methylmercury, associated or not, and the possible protective effect of niacin on this exposure

Author(s)

Eloísa Silva de Paula

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2016-04-07

Examining board members

Fernando Barbosa Junior; Gustavo Rafael Mazzaron Barcelos; Maria de Lourdes Pires Bianchi; Wilma de Grava Kempinas

• Advisor: Fernando Barbosa Junior; Denise Grotto

Abstract

In Brazil, riverside populations of the Amazon are exposed to methylmercury (MeHg) and lead (Pb) coming respectively from contaminated fish and cassava flour. Although the toxicity of these elements has been explored for some time, little is known about the effects of chronic exposure at low doses and even less about the simultaneous exposure. Thus, this work aimed to evaluate the occurrence of biochemical, genotoxic and oxidative stress related effects, resulting from chronic exposure of rats at low doses of MeHg and Pb, associated or not, as well as the tissue distribution of these elements. Additionally, the effects of co-administration of the antioxidant vitamin niacin (NA) on the toxic effects were investigated. For this, male Wistar rats were divided into 8 groups (n = 6): Control group; MeHg group, received MeHg chloride (140 ?g/Kg/day) by gavage; Pb group, received Pb acetate (648 ?g/Kg/day) by gavage; MeHg + Pb group, received MeHg (140 ?g/Kg/day) and Pb (648 ?g/Kg/day) by gavage. Parallel groups (NA; NA + MeHg; NA + Pb and NA + MeHg + Pb) received the same treatment associated with niacin supplementation (50 mg/kg/day) added to the water. The treatment lasted 92 days. Biochemical parameters such as total and fractions cholesterol, glucose, hepatic enzyme activity such as aspartate transaminase (AST) and alanine transaminase (ALT), and hemoglobin were determined. Oxidative stress markers such as total thiols (GSH); lipid peroxidation, measured by malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) concentrations; besides the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) antioxidant enzymes were evaluated in treated and non-treated animals. Also, the concentration of plasmatic nitric oxide (NO) and genotoxicity by the Comet Assay was assessed. Levels of mercury (Hg) and Pb were determined in whole blood and tissues of animals by ICP-MS. Low doses of exposure to MeHg caused reduction of CAT activity in the brain and reduction of GSH concentrations in the blood and liver of animals, besides genotoxicity and lipid peroxidation, as evidenced by the increase levels of MDA and TBARS in plasma and brain of rats. Animals exposed to MeHg still had increased ALT activity and decreased plasmatic NO levels. Levels of Hg were found higher in kidney, followed by blood and brain. Pb exposure alone promoted reduction of GSH concentration and CAT activity, and induced lipid peroxidation in the brain of rats. Moreover, genotoxicity, and reduction of hemoglobin and plasmatic NO levels were also observed in the group of animals treated only with Pb. The highest Pb levels were observed in bone (femur) > kidney > brain > blood. Simultaneous exposure to MeHg and Pb did not result in synergistic toxic effects. Considering parameters such as plasmatic NO and GSH levels in blood, liver and brain, the joint exposure to metals antagonized the effects produced by each metal individually. However, the MeHg/Pb co-exposure also promoted genotoxicity and lipid peroxidation. On the other hand, administration of niacin exhibited protective effects under the changes triggered by exposure to metals without altering the concentration and distribution of these metals in the organs/tissues of animals. Taken together, our results demonstrated that exposure to MeHg and Pb, even at low doses, are toxic to iv rodents. Moreover, since niacin presented relevant antioxidant and antigenotoxic effects, supplementation with this vitamin can be an alternative to mitigate the toxic effects resulting from exposure to MeHg and/or Pb. (AU)

• FAPESP's process: 13/05560-4 - Concomitant exposure to methylmercury and lead in rats: distribution in the body, evaluation of genotoxicity and oxidative stress parameters, and possible protective effect of the fruit maná cubiu (Solanum sessiliflorum Dunal)
• Grantee: Eloisa Silva de Paula
• Support Opportunities: Scholarships in Brazil - Doctorate