Thiamethoxam evoked neural oxido-inflammatory stress in male rats through modulation of Nrf2/NF-kB/iNOS signaling and inflammatory cytokines: Neuroprotective effect of Silymarin.

Thiamethoxam (TMX), a neonicotinoid insecticide, is a widely used insecticide with neurotoxic potential. Silymarin (SM), a milk thistle-derived flavonoid, is known with its promising biological activities. This study explored the neuroprotective effects of SM against TMX-triggered cortical injury in male rats. Animals were divided into four groups and treated daily either with SM (150 mg/kg), TMX (78.15 mg/kg), or both at the aforementioned doses for 28 days. Our results revealed marked declines in cortical SOD and CAT activities with elevations in MDA, IL-1b and TNF-α levels in TMX-treated rats. Further, TMX induced down-regulation in the gene expressions of Sod, Cat, Gpx, and Nrf-2, with up-regulation in the gene expressions of IL-1b, IL-6, iNOS, TNF-α and NF-kB. Interestingly, pre-treatment with SM provided a notable neuroprotective action against TMX-mediated cortical damage that indicates its promising antioxidant and anti-inflammatory activities. This effect may be mediated by Nrf2/NF-kB/iNOS signalling and suppression of excess free radicals and production of inflammatory cytokines. In brief, SM could be a promising therapeutic agent against TMX-mediated neural complication via its antioxidant and anti-inflammatory properties. PRACTICAL APPLICATIONS: The using of neonicotinoids as thiamethoxam is recently increased and is associated with brain damage. TMX induced excessive oxidative and inflammatory damage. Therefore, new therapeutic approaches are needed to counteract its adverse effects on the nervous system. SM, a flavonoid, is extracted from the seeds and fruits of milk thistle. Due to its potent antioxidative activity, SM have been applied to mitigate the oxidative stress as well as inflammatory disorders. Herein, we examined the potential therapeutic role of SM against TMX-induced brain oxidative stress and inflammation in rats through evaluating oxidative markers, inflammatory response, and histopathological changes in the brain cortical tissue.