Telmisartan inhibits the non-canonical TGF-β/JAK2/STAT3 signaling pathway and prevents carbon tetrachloride-induced liver fibrosis in rats

This research purpose was to assess the potential inhibitory action of telmisartan on IL6/JAK2/STAT3 pathway in carbon tetrachloride (CCl4)-induced liver toxicity in rats. Carbon tetrachloride (1ml/kg; 50% in corn oil ) was injected two times/week for 8 weeks in male Sprague-Dawley rats. Intoxicated rats with CCl4 were concurrently treated daily with telmisartan (10 mg/kg) for eight weeks. Telmisartan treatment markedly ameliorated the biochemical and the histological deviations in CCl4 intoxicated rats. As, telmisartan treatment mended the elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in CCl4 intoxicated group. Additionally, telmisartan significantly reduced oxidative stress parameters as lipid peroxidation and markedly increased total antioxidant capacity in liver tissue of CCl4 treated rats. Also, telmisartan treatment reduced inflammation as evidenced by the distinct decrease in hepatic interleukin-6 (IL-6) level. These biochemical results were further supported by the improvement in the altered histopathological architecture of liver tissue. Interestingly, telmisartan treatment down-regulated hepatic expression of JAK2/STAT3 in CCl4-intoxicated animals. Conclusively, the hepatoprotective action of telmisartan against CCl4-induced liver toxicity might be through mitigating oxidative stress, inflammation, and targeting IL-6/JAK2/STAT3 pathway.