Ameliorative effects of vitamin C on short-term sensorimotor and cognitive changes induced by acute chlorpyrifos exposure in Wistar rats

Abstract

Human and experimental animal studies have shown long- and short-term neurological sequelae following acute organophosphate (OP) exposure. Although the main molecular mechanism of OP neurotoxiicty involves acetylcholinesterase (AChE) inhibition, studies have also implicated the induction of oxidative stress. The present study was therefore aimed at evaluating the effect of acute chlorpyrifos (CPF) exposure on short-term sensorimotor and cognitive changes in Wistar rats, the role of brain lipoperoxidative changes and the effect of pretreatment with vitamin C. Twenty-eight rats divided into four groups of seven rats in each group served as subjects for this study. Rats in group I were given soya oil (2 ml/kg) while those in group II were dosed vitamin C (100 mg/kg). Group III were administered CPF only (42.5 mg/kg ∼50% of LD₅₀), while group IV were pretreated with vitamin C (100 mg/kg) and then exposed to CPF (42.5 mg/kg), 30 min later. The regimens were administered once orally and the animals were examined for clinical signs, death and subjected to periodic neurobehavioral evaluation for motor strength, coordinated gait, neuromuscular coordination, learning and memory. At the end of 8 weeks of evaluation, the rats were sacrificed and the brain tissue evaluated for AChE activity and malonaldehyde (MDA) concentration, as an index of lipoperoxidative changes. The rats administered with CPF showed deficits in motor strength, coordinated gaits, neuromuscular coordination, learning and memory, slight decrease in AChE activity and an increase in brain MDA concentration. Pretreatment with vitamin C improved the neurobehavioral deficits and AChE activity, and caused a significant reduction in MDA concentration. In conclusion, the study has demonstrated that acute CPF exposure in Wistar rats caused short-term impairment in sensorimotor and cognitive functions partly due to brain lipoperoxidative changes, which were ameliorated by pretreatment with vitamin C.