Purpose: Liver fibrosis stems from changes in fibrotic genes expression in response to tissue damage in various chronic liver diseases, with no effective therapeutic program at present. This study designed to explore the possible protective effects and the molecular targets of aliskiren (ALS) and fenofibrate (FENO) against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Methods: Wister albino rats had been injected with 0.4ml/kg 50% CCl4, three times/week for eight weeks, to establish liver fibrosis model. Concurrently, ALS (25mg/kg/day) and/or FENO (25mg/kg/day) were orally administrated for 8 weeks to rats CCl4 intoxicated.
Results: Treatment with ALS and/or FENO ameliorated oxidative stress and hepatocellular damage in CCl4-intoxicated rats as indicated by the marked reduction in hepatic lipid peroxidation and serum transaminases with concomitant significant increase in hepatic superoxide dismutase (SOD) as well as glutathione (GSH) content. The magnitude of liver inflammation and fibrosis was also alleviated by both medications, as is evident from the substantial decrease in hepatic proinflammatory and profibrotic cytokines such as tumor necrosis factor a (TNF-a), interlukin-6, (IL6), C-reactive protein (CRP) and transforming growth factor-β1 (TGF-β1) with restrain in fibrous deposition alongside architecture alteration that was shown upon histopathological examination. Additionally, simultaneous administration of ALS with FENO downregulated hepatic p-Smad3 protein and increased hepatic growth factor (HGF) expression in CCl4-intoxicated rats. Conclusion: Conclusively, this study highlights the hepatoprotective effect of ALS and FENO and imply that their anti-fibrotic mechanism involves blockade of TGF-β1/Smad signaling pathway, induction of HGF expression, besides modulation of inflammation as well as oxidative stress.