Inhibition of activated factor X; a new pathway in ameliorating carbon tetrachloride–induced liver fibrosis in rats

Activated factor X has a central role in the coagulation activation and also contributes to chronic inflammation and tissue fibrosis. In this study, rivaroxaban, a direct factor X inhibitor, attenuates liver fibrosis induced by carbon tetrachloride (CCl4). Male rats were randomly allocated into three groups: a control group, CCl 4 fibrotic group, and CCl 4+rivaroxaban (5 mg/kg) group. Liver fibrosis was induced by subcutaneous injection of CCl 4 twice a week for 6 weeks. Rivaroxaban significantly restored the biochemical parameter including inflammatory and fibrosis markers with histopathological evidence using routine and Masson trichrome staining. It reduced also the expression of tissue factor, fibrin, transforming growth factor and α‐smooth muscle actin in the liver tissues. This concludes that rivaroxaban attenuates liver injury caused by CCl 4, at least in part by inhibiting coagulation and proinflammatory activation. In conclusion, rivaroxaban may be used for the management of liver fibrosis. Graphical shows the pathological activation of the factor Xa‐PAR‐2 system, which induces a profibrogenic effect in hepatic stellate cells, fibrin deposition, and cytokine release with the protective role of factor X inhibitor, rivaroxaban.