Thiamethoxam (TMX) is a non-mutagenic neonicotinoid insecticide that is widely used to combat different types of insects. The hepatotoxicity and carcinogenicity of TMX have been approved previously in mice but not in rats. However, the TMX-induced hepatotoxic and pro-carcinogenic effects on rabbits remain unclear. The present study elucidated the roles of oxidative stress, pro-inflammatory cytokines, and apoptosis-related genes in the hepatotoxic and carcinogenic effects of TMX on rabbits. Sixteen male rabbits were equally divided into two groups; eight rabbits orally treated with TMX at a dose of 250 mg/kg b.w for 90 successive days. Hepatotoxic effects of TMX were evidenced by attenuation of liver enzyme activities, elevation of bilirubin levels, and alterations in the hepatic architecture, including hepatocyte death by necrosis and apoptosis, lymphocyte infiltration and fibrosis. TMX induced oxidative stress, as evidenced by the significant increases in malondialdehyde levels and antioxidant enzyme (glutathione transferase and catalase) activities along with a decrease in glutathione levels. TMX also up-regulated the mRNA levels of interleukin-6 (1.6-fold) and B cell lymphoma-2 (1.8-fold) and down-regulated the mRNA level of the tumor necrosis factor-α (0.8-fold), indicating its effects on cell survival and proliferation through the inhibition of apoptosis. Interestingly, the elevated level of carcinoembryonic antigen and the appearance of ground glass-like hepatocytes suggested that TMX exerted a pro-carcinogenic effect. In conclusion, TMX exerts potentially hepatotoxic and pro-carcinogenic effects on rabbits by modulating oxidative/antioxidative status and pro-inflammatory cytokine production, inhibiting apoptosis and activating cell survival pathways.

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The current study was instigated by investigating the ameliorative potential of Ornipural® solution against the hepato-renal toxicity of malathion. A total number of 35 male Wistar albino rats were divided equally into five groups. Group 1 served as control and received normal saline intraperitoneally. Group 2, the sham group, were administered only corn oil (vehicle of malathion) orally. Group 3 was orally intoxicated by malathion in corn oil at a dose of 135 mg/kg BW via intra-gastric gavage. Group 4 received malathion orally concomitantly with Ornipural® intraperitoneally. Group 5 was given Ornipural® solution in saline via intraperitoneal injection at a dose of (1 mL/kg BW). Animals received the treatment regime for 30 days. Histopathological examination revealed the harmful effect of malathion on hepatic and renal tissue. The results showed that malathion induced a significant decrease in body weight and marked elevation in the activity of liver enzymes, LDH, and ACP. In contrast, the activity of AchE and Paraoxonase was markedly decreased. Moreover, there was a significant increase in the serum content of bilirubin, cholesterol, and kidney injury markers. A significant elevation in malondialdehyde, nitric oxide (nitrite), and 8-hydroxy-2-deoxyguanosine was observed, along with a substantial reduction in antioxidant activity. Furthermore, malathion increased tumor necrosis factor-alpha, the upregulation of IL-1B, BAX, and IFN-β genes, and the downregulation of Nrf2, Bcl2, and HO-1 genes. Concurrent administration of Ornipural® with malathion attenuated the detrimental impact of malathion through ameliorating metabolic biomarkers, restoring antioxidant activity, reducing the inflammatory response, and improving pathologic microscopic alterations. It could be concluded that Ornipural® solution demonstrates hepatorenal defensive impacts against malathion toxicity at biochemical, antioxidants, molecular, and cellular levels.

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