Evaluation of the Possible Antifibrotic effect of Aliskiren, Valsartan, Chloroquine, Zafirlukast and Colchicine on Liver Fibrosis Induced by Carbon Tetrachloride in Rats

The present work aims to study the possible anti-fibrotic effect of aliskiren, valsartan, chloroquine, zafirlukast in comparison to colchicine on prevention of liver fibrosis in experimental model of liver fibrosis induced by carbon tetrachloride (CCL4) in rats. Hepatic fibrosis was induced by CCL4 (33mg/kg, oral) for 6 weeks. The rats were treated with either aliskiren (10 mg/kg), valsartan (50 mg/kg), chloroquine (5 mg/kg) zafirlukast (5 mg/kg) or colchicine (50 µg/kg) simultaneously with CCL4 treatment. Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Egypt, Between June 2013 and August 2014. We included 56 Spague Dawely rats. All are exposed to induction of hepatic fibrosis by CCL4 for 6 weeks. After the end of treatment, blood samples were obtained to assess liver function tests, plasma renin activity. Then, liver tissues were obtained to assess hepatic fibrosis markers (hydroxyproline and transforming growth factor-β1) and oxidative stress markers (reduced glutathione and malondialdehyde). Moreover, liver specimens from each group were processed for histo-pathological studies. Treatment with either colchicine, aliskiren, valsartan, chloroquine or zafirlukast simultaneously with CCL4 for 6 weeks resulted in marked decrease in the amount of collagen fibers around the central veins. There is also improvement liver function tests, fibrosis markers and oxidative stress markers. Sample size is 8 rats in each group. Data were analyzed using one way analysis of variance followed by post hoc test of Tukey's Honestly Significant Difference. P-value of less than 0.05 was considered to be significant. This study demonstrated the promising anti-fibrotic effect of aliskiren, valsartan, chloroquine, zafirlukast and colchicine. These drugs significantly prevent progression of liver fibrosis induced by CCL4 in rats; probably through, inhibition of renin angiotensin system, anti-inflammatory, anti-oxidant effects, and decrease TGF-β1 level so,