Lycopene Ameliorates Chlorpyrifos-induced Neurotoxicity via Antioxidant and Anti-inflammatory Mechanisms in Rats

Background: Chlorpyrifos (CPF) is a common organophosphate insecticide with toxic effects on the brain, nervous system, and other organs. Objectives: This study was designed to determine the neuroprotective efficacy of lycopene, a potential carotenoid, on CPF-induced neuronal damage in male rats. Methods: Eighteen male Wistar rats were randomly divided into three study groups (n=6): control group received only vehicle, CPF-treated group received CPF (6 mg/kg/d), and CPF + lycopene-treated group received CPF followed by lycopene (10 mg/kg/d). After 28 days of treatment, the animals were sacrificed to assess anti-oxidative and anti-inflammatory markers. Results: CPF intoxication significantly inhibited the acetylcholinesterase (AChE) in brain cells. As a result, excess choline accumulates in neurons, impairing neurochemical homeostasis and cognitive function. Glutathione S-transferase, catalase, peroxidase, and superoxide dismutase activities and reduced glutathione content were significantly decreased in the CPF-treated group due to excess accumulation of reactive oxygen species (ROS) in brain cells. This result is also reflected by the elevated malondialdehyde (MDA) levels and conjugated diene. Thus, cellular damage in the brain ensues. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), the proinflammatory mediators, increased in brain tissue in the CPF-treated group. After cerebrum and cerebellum histological analysis, partial neuronal necrosis and damage in Purkinje and granular cells were observed. All the above-mentioned parameters of brain tissue were significantly recovered towards the control level in the lycopene-treated group. Conclusion: We may conclude that lycopene protects rat brain tissue against CPF-induced neurotoxicity by acting as an antioxidant, anti-inflammatory, and anticholinergic agent.