Aim: The aim of the current article was to investigate the possible antifibrotic and antioxidant effects of a new angiotensin II type I receptor blocker, olmesartan medoxomil, using low and high dose on CCl4-induced liver fibrosis. Methods : Fifty adult male albino rats were randomly divided into five equal groups, including normal control rats (group I), control vehicle rats (group II), model group (group III), and two treated groups with either low (group IV) or high dose (groupV) of olmesartan medoxomil. Except for rats in control groups, all rats were injected subcutaneously with 1ml/kg CCl4 at a ratio of 1:1 with olive oil, twice a week for 12 weeks. Olmesartan groups were given (0.6 and 6 mg/kg/day) via gavage. At the end of the study period, blood samples and liver tissues were collected and subjected to the biochemical and histopathological examination. Liver function, oxidative stress markers in liver tissues and a marker of liver fibrosis (liver hydroxyproline content) were assessed. In addition to histopathological examination of liver tissues. Results: CCl4-induced liver fibrosis was manifested by a significant elevation in activities of AST, ALT, ALP and serum bilirubin and a significant decrease in serum albumin. In addition to a significant elevation of liver fibrosis marker (hydroxyproline content of the liver). At the same time, there was a significant increase of lipid peroxidation measured as (MDA) and a significant decrease of (GSH) and (SOD) content in the liver tissue homogenate. Our results revealed that the rats treated with low dose of olmesartan concomitant with CCl4 showed a non-significant decrease in liver enzymes (AST, ALT, ALP) and bilirubin when compared with model group, while the rats treated with high dose of olmesartan concomitant with CCl4 resulted in a significant decrease in the previous parameters. At the same time, low dose olmesartan treated rats showed a non-significant difference in albumin as compared to model group while high dose olmesartan treated rats showed a significant elevation in serum albumin. Hydroxyproline content of the liver showed improvement evidenced by a significant decrease in its level in both olmesartan treated groups when compared with CCl4-treated rats. As regarding lipid peroxidation markers, administration of low or high dose of olmesartan concomitant with CCl4 exhibited a significant decrease in liver MDA and a significant increase in both GSH and SOD. The biochemical observations were supported by histopathological examination of liver sections. Conclusion: olmesartan medoxomil with low or high dose produced a benificial effects on CCl4-induced liver fibrosis through its antifibrotic and antioxidant effects.
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