Evaluation of Resveratrol as a Therapeutic Agent Against Nonylphenol Induced Neurotoxicity in Rats

Abstract

Environmental pollution has led to the widespread presence of neurotoxic substances, including endocrine-disrupting chemicals such as nonylphenol. Nonylphenol is widely utilized in industrial and consumer products, including polyvinyl chloride pipes, and its persistence in the environment and accumulation in body tissues pose serious health risks. Exposure to nonylphenol disrupts hormonal balance, induces oxidative stress, and triggers inflammation, contributing to cognitive dysfunction, behavioral changes, and neurodegenerative disorders. This study investigates the therapeutic role of resveratrol, a polyphenolic agent exhibiting antioxidant, anti-inflammatory, and neuroprotective properties, against nonylphenol-induced neurotoxicity. Thirty-eight male Wistar rats were allocated into four groups, each having 8 rats: a control group, a neurotoxin-treated group receiving nonylphenol, and two treatment groups receiving low (5 mg/kg body weight) and high (20 mg/kg body weight) doses of resveratrol along with nonylphenol. Behavioral assessments, including the Morris Water Maze and Open Field Test, were conducted to evaluate spatial learning, cognitive ability, anxiety, and exploratory activity. Results showed significant improvements in resveratrol-treated groups, with the low dose exhibiting superior efficacy compared to the high dose. Biochemical analyses revealed a decline in oxidative stress levels and restoration of antioxidant enzyme activity, including catalase, superoxide dismutase, and glutathione peroxidase, in the cortex and hippocampus of resveratrol-treated groups. Additionally resveratrol attenuated neuroinflammation and re-established normal neurochemical balance. Molecular docking studies demonstrated strong binding affinities of resveratrol with key molecular targets involved in nonylphenol-induced neurotoxicity, including STAT3, NFKB1, and MAPK3. Further analysis with Gene Ontology enrichment and kegg pathway analysis highlighted resveratrol's role in modulating pathways associated with oxidative stress, inflammation, apoptosis, and synaptic plasticity. The findings indicate that resveratrol, specifically at a lower dose, is potent in mitigating nonylphenol-driven neurotoxicity by reducing oxidative stress, alleviating inflammation, and promoting neuronal health. Our results provide a foundation for developing therapeutic strategies to alleviate the adverse effects of environmental neurotoxins and underscore the potential of resveratrol as a neuroprotective agent.