Oxidative stress involvement in chronic chlorpyrifos-induced hepatocellular injury: Alleviating effect of vitamin C

Abstract

Introduction: Chlorpyrifos (CPF), a phosphorothionate chlorinated organophosphate (OP) insecticide is widely used in agriculture and public health. Like other OP insecticides, its main mechanism of toxicity is the inhibition of acetylcholinesterase (AChE) leading to cholinergic syndrome. Since toxicity occurs at doses that do not inhibit AChE or long after its restoration, other mechanisms including the induction of oxidative stress have been widely implicated. The present study was aimed at evaluating the mitigating effect of vitamin C on CPF-induced hepatocellular injury in Wistar rats. Methods: Twenty adult male Wistar rats were divided into 4 groups of five animals in each group. The four groups were exposed by gavage to soya oil (2 ml/kg), vitamin C (100 mg/kg), CPF (10.6 mg/kg~1/8th LD50) and vitamin C (100 mg/kg) + CPF (10.6 mg/kg; 30 min later), respectively for 17 weeks. The sera obtained from blood samples collected from the animals were analysed for the levels of total proteins, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), g-glutamyl transferase (GGT) while globulin concentration and albumin/globulin ratio were calculated. The liver homogenate was evaluated for the levels of malonaldehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), and histological changes. Results: The study showed that CPF altered the levels of the serum hepatic enzymes, hepatic MDA SOD and CAT, in addition to inducing hepatocellular degeneration. All these parameters were alleviated by pretreatment with vitamin C. Significance: CPF-induced hepatocellular injury which was partly due to oxidative changes was mitigated by vitamin C partly due to its antioxidative activity.