Protective effect of fisetin against subchronic chlorpyrifos-induced toxicity on oxidative stress biomarkers and neurobehavioral parameters in adult male albino mice

Abstract

Chlorpyrifos (CPF), a chlorinated organophosphate insecticide that is widely used in agriculture and public health, has neurotoxic effects in animals. In addition to acetylcholinesterase inhibition, CPF has been shown to induce alterations such as oxidative stress and lipid peroxidation. Fisetin is a dietary flavonol that protects the brain tissue against oxidative stress by modulating the activity of antioxidant enzymes. This study was designed to investigate the protective role of fisetin against brain oxidative damages and neurobehavioral parameters induced by subchronic oral exposure to CPF in albino mice. Adult albino mice (males, n = 32, weighing 20 ~ 25 g) were assigned randomly into 4 groups and treated accordingly for 7 weeks as follows: Group 1(S/OIL): served as the control group and were given 2 ml/kg of soya oil; Group 2 (CPF): received CPF (6.6 mg/kg; 1/5th of the LD50); Group 3 (FIS): fisetin (15 mg/kg) and Group 4 (FIS + CPF): received fisetin at 15 mg/kg, followed by CPF (6.6 mg/kg) 30 min later. Co-treatment with FIS + CPF mitigated the increase in brain malondialdehyde concentration (0.28 ± 0.02 nmol/mg) and orchestrated the increase in the activities of catalase (81.35 ± 7.26 µ/mg), superoxide dismutase (93.03 ± 6.63 IU/mL), glutathione peroxidase (68.76 ± 3.554 nmol/mL) and acetylcholinesterase (11.59 ± 0.72 nmol/min/mL) when compared to the CPF group. The result showed that deficits in motor strength and excitability scores induced by subchronic CPF were mitigated by fisetin administration. It was concluded that fisetin has a protective potential in mitigating against oxidative stress and damages in the brain tissues, induced by subchronic exposure to CPF in adult male albino mice.