Maneb disturbs expression of superoxide dismutase and glutathione peroxidase, increases reactive oxygen species production, and induces genotoxicity in liver of adult mice

Maneb (MB), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. However there is a lack of informations regarding the risks arising from MB exposure on non target organisms, especially mammals. The aim of this study was to investigate the morphological, biochemical and molecular aspects of liver injury after exposure of mice to MB. Four doses of MB corresponding to 1/8 (group D1), 1/6 (group D2), 1/4 (group D3), and 1/2 (group D4) of lethal dose (DL50=1500 mg/kg body weight) were administered to adult mice. Oxidative stress parameters were also objectified by molecular and histological endpoints in the liver. Maneb caused hepatotoxicity as characterized by the significant increase in the levels of malondialdehyde and protein oxidation marker, advanced oxidation protein products (AOPP). The activities of catalase, glutathione peroxidase, superoxide dismutase and the levels of glutathione decreased significantly in all treated mice, while vitamin C levels decreased only in group D4. We also noted a significant decrease in gene expression of superoxide dismutase and glutathione peroxidase enzymes. Maneb caused nucleic acids degradation testifying its genotoxicity. Yet, biochemical markers in plasma showed a decrease in total protein and an increase in aspartate, alanine amino transferases and bilirubin levels in all treatment groups. Moreover, plasma levels of cholesterol, triglycerides and low density lipoprotein-cholesterol significantly increased, while those of high density lipoprotein-cholesterol decreased. These biochemical alterations were correlated with significantly histological changes. Our data showed, for the first time, that intraperitoneal injection of very high non environmentally relevant MB concentrations to adult mice resulted in oxidative stress leading to hepatotoxicity and the impairment of defense systems, confirming the pro-oxidant and genotoxic effects of this fungicide.