Neurotoxicity of Acetamiprid and Fenpyroximate in Male Rats

ABSTRACT Acetamiprid (ACE), a neonicotinoid insecticide, and fenpyroximate (FEN), a pyrazole acaricide, are widely applied in agriculture and may pose neurotoxic risks to mammals. The present work evaluated the individual and combined neurotoxic effects of acetamiprid and fenpyroximate at oral doses corresponding to 1/40 and 1/20 of the LD 50 in adult male rats for 28 days. Neurotoxicity was assessed through biochemical markers of oxidative stress, neurotransmitter alterations, apoptotic progression, neuroinflammation, and histopathological examination of brain tissue. Sixty adult male albino rats were divided into six groups ( n = 10): Control, ACE (1/40 LD 50 ), ACE (1/20 LD 50 ), FEN (1/40 LD 50 ), FEN (1/20 LD 50 ), and combined ACE+FEN (1/40 LD 50 of each) and statistical significance was determined at p < 0.05. Co‐exposure to ACE and FEN produced markedly greater toxicity than either pesticide alone, evidenced by a sharp rise in malondialdehyde (MDA) levels and significant suppression of the antioxidant biomarkers superoxide dismutase (SOD), catalase (CAT), and glutathione‐S‐transferase (GST) activities ( p < 0.05). Both chemicals induced strong, dose‐dependent inhibition of acetylcholinesterase (Ach E), leading to acetylcholine accumulation and profound dopamine depletion. Molecular analysis showed downregulation of TP53 and upregulation of COX‐2, with the most pronounced dysregulation under combined exposure. Serum interleukins (IL‐1β, IL‐6, IL‐8), and tumor necrosis factor‐alpha (TNF‐α) levels were significantly elevated, confirming a robust inflammatory response. Our histopathological findings revealed severe neurodegenerative lesions consistent with biochemical findings. Collectively, ACE and FEN synergistically exerted distinct neurotoxic effects by inducing oxidative damage, neuroinflammation, neurotransmitter imbalance, and neuronal degeneration. These findings highlight the potential health risks of combined pesticide exposure and underscore the need for stricter regulatory assessment of mixture toxicity in mammalian systems.