Effect of combined exposure of commonly used organophosphate pesticides on lipid peroxidation and antioxidant enzymes in rat tissues

Organophosphate compounds are among the most widely used synthetic chemicals for controlling a wide variety of pests. Organophosphate (OP) poisoning continues to be major cause of morbidity and mortality in the third world countries. Indiscriminate use of these pesticides tends to leave residues on the objects of the environment. Present study is aimed to compare the potential of three commonly used OP pesticides, chlorpyrifos (CPF), methyl parathion (MPT) and malathion (MLT), to generate oxidative stress in rat tissues and to evaluate whether the combined exposure of these pesticides exerts synergistic or antagonistic effects. Results of the present study showed that CPF, MPT and MLT exposure to rats caused accumulation of malondialdehyde (MDA) and 4-hydroxynonanal (4HNE), the two major end products of lipid peroxidation, in liver, kidney, brain and spleen of rats. Combined exposure of these pesticides also resulted in accumulation of MDA and 4HNE in rat tissues but the increase was almost of the same order as observed in rat tissues given these pesticides singly. Exposure with CPF, MPT and MLT singly or in mixture, caused dose-dependent decrease in the activities of antioxidant enzymes namely, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in rat tissues when compared with control, and the decrease observed was of the same order in all the groups. Acetylcholinesterase (AChE) activity, an indicator of OP poisoning, was also decreased in rat tissues in dose-dependent manner in CPF, MPT, MLT and mixture treated group. Differential increase in the levels of cytochrome P450 (cyt P450) in hepatic and extra-hepatic tissues of rats given CPF, MPT or MLT singly or in mixture, indicate different rates of metabolism of these pesticides. Results of the present study clearly show that CPF, MPT and MLT exposure singly or in mixture, induced oxidative stress in rat tissues which may be the major contributor of the overall toxicity of the OP pesticides. Combined exposure of these pesticides does not seem to potentiate the toxicity of each other and their toxic effects are not additive.