Aliskiren attenuates chronic carbon tetrachloride-induced liver injury in mice

Background Increased angiotensin II (Ang II) plays an important role in liver inflammation and fibrogenesis. Chronic administration of aliskiren, a newly developed direct renin inhibitor, decreases Ang II in the hypertensive patients and animals. Aims Our study aims to evaluate the possible protective effects of chronic administration of aliskiren in a chronic liver injury model. Methods C57BL6 mice were injected intraperitoneally with carbon tetrachloride (CCl4) to induce chronic liver injury. The injured mice were randomly assigned to aliskiren-treated (25 mg/kg per day for 2 weeks, the CCl4 + Ali group) or untreated group (the CCl4 group). Mice without CCl4 and aliskiren administration served as the normal control. Results In the CCl4-injured mice, aliskiren attenuated liver inflammation and fibrosis. The levels of hepatocyte apoptosis, lipid peroxidation production, the activation of hepatic stellate cells and Kupffer cells, hepatic expression of p47 phox, inflammatory mediators and profibrotic markers were reduced in the CCl4 + Ali group. Furthermore, aliskiren decreased Ang II, activated the renal expression of renin, but down-regulated the hepatic expression of renin and renin receptor in the CCl4-injected mice. Conclusions Aliskiren attenuates chronic liver injury in the CCl4-treated mice by reducing Ang II. Direct renin inhibition may serve as a potential treatment for chronic liver injury.