JAK inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

Abstract

Background: To investigate the potential effects of JAK inhibitor Tofacitinib in mice with lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced acute hepatitis, including the production of inflammatory cytokines, the induction of hepatocytes apoptosis and the degree of liver injury were determined. Methods and Results: The plasma levels of ALT and AST and liver activities of caspase-3, caspase-8, caspase-9 were determined by colorimetric assay kits. The plasma levels of TNF-a and IL-6 were detected by ELISA kits. Hepatocellular apoptosis was observed by TUNEL assay. HE staining was used to observe the histopathological changes. The expression of cleaved caspase-3 was analyzed by western blot.The results indicated that treatment with Tofacitinib in LPS/D-Gal-induced acute liver injury decreased the levels of aminotransferases, attenuated the histological abnormalities in liver and decreased the plasma levels of TNF-a and IL-6. In addition, Tofacitinib suppressed the activation of caspase cascade, decreased the expression of cleaved caspase-3 and reduced the number of TUNEL-positive cells. Conclusion: Treatment with Tofacitinib alleviated LPS/D-Gal-induced acute hepatitis. JAK maybe become a promising target for the control of inflammation-based liver disorders.