Chlorpyrifos (CPF) is a widely used organophosphate insecticide with several harmful effects. N-acetylcysteine (NAC) represents an ideal antixenobiotic; it can directly enter endogenous biochemical processes and is used as adjunctive treatment for psychiatric disorders. We aimed to evaluate the neuroprotective effect of NAC as an antioxidant drug against CPF-induced neurotoxicity in adult male albino rat brains. Twenty-eight male Wister rats were allocated into four groups (n = 7) and were administered the following for 28 days: group I (control group), physiological saline (0.9% NaCl); group II (CPF group), 10 mg/kg body weight (BW) CPF; group III (NAC group), 100 mg/kg BW NAC; and group VI (CPF+NAC group), NAC 1 h before CPF. CPF intoxication resulted in acetylcholinesterase inhibition, reduced glutathione content, and elevated levels of malondialdehyde and nitric oxide, which are oxidative stress biomarkers. CPF also depleted the activity of antioxidant enzymes, superoxide dismutase and catalase, and levels of inflammatory mediators, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β. Levels of vascular endothelial growth factor, Bax, and the proapoptotic caspases-3 also increased, while brain-derived neurotrophic factor level decreased. Additionally, CPF significantly diminished Bcl-2 (an antiapoptotic protein) in rat brain cortical tissue. NAC treatment was found to protect brain tissue by reversing the CPF-induced neurotoxicity. Our results show the antioxidant, antiinflammatory, and antiapoptotic effects of NAC on CPF-induced neurotoxicity in rat brain tissue.
Keywords: Antioxidant; Chlorpyrifos; N-Acetylcysteine; Neurotoxicity; Oxidative Stress.