Abstract
Overdose of acetaminophen (APAP) is often associated with hepatotoxicity. Carfilzomib (CFZ) shows multiple pharmacological activities including anti‐inflammatory potential. Therefore, this study was undertaken to evaluate the possible therapeutic effects of CFZ against APAP‐induced hepatotoxicity. Hepatotoxicity was induced by administration of APAP (350 mg/kg, intraperitoneal). Mice were given CFZ (0.125, 0.25, or 0.5 mg/kg, intraperitoneal) 1.5 h after APAP administration. Animals were sacrificed on 6 h and blood and liver tissue samples were collected for analysis. In CFZ‐post‐treated group, there was significant and dose‐dependent decrease in serum alanine aminotransferase levels. The level of tumor necrosis factor‐α (TNF‐α), reactive oxygen species, and NO decreased, whereas glutathione increased significantly by CFZ post‐treatment. Upregulated mRNA expression of COX‐II and iNOS were significantly downregulated by CFZ post‐treatment. CFZ may exert its hepatoprotective action by alleviating inflammatory, oxidative, and nitrosative stress via inhibition of TNF‐α, COX‐II, and iNOS.