Toxicological impact of Thiamethoxam on adult male rats: Histopathological, biochemical, and oxidative DNA damage assessment.

Background: Thiamethoxam (TMX), a widely used second-generation neonicotinoid insecticide, has raised concerns due to its toxic effects on non-target species, including mammals. Its prolonged use is associated with hepatotoxicity, nephrotoxicity, and reproductive damage. Objectives: This study evaluates the dose-dependent biochemical, histopathological, and genetic toxic effects of TMX in male albino rats, emphasizing its impact on the liver, kidney, and reproductive systems. Materials and methods: Forty male Wistar albino rats were assigned to control and three experimental groups treated with TMX at 26, 39, and 78 mg/kg/day over eight weeks. Key biochemical markers such as Alanine transaminase (ALT), Aspartate transaminase (AST), urea, creatinine and oxidative stress indicators (Catalase (CAT), Glutathione (GSH), Malondialdehyde (MDA), and reproductive parameters (testosterone, sperm count, and motility) were analyzed. Histopathological examination of the liver, kidney, and testes was performed, alongside evaluation of Deoxyribonucleic Acid (DNA) damage in testicular tissue. Results: TMX exposure caused significant dose-dependent increases in liver and kidney function markers and oxidative stress. Reproductive toxicity was evident, with reduced testosterone levels, impaired sperm parameters, and histopathological damage to testicular tissue. Notably, TMX induced oxidative DNA damage in testicular tissue, as indicated by increased levels of 8-hydroxy-2'-deoxyguanosine. Conclusions: This study highlights TMX's systemic toxicity in a dose-dependent manner, with oxidative stress and DNA damage as key mechanisms. The findings underscore the need for stricter regulatory measures and further exploration of protective strategies to mitigate TMX-induced toxicity.