Abstract
The renin-angiotensin system (RAS) plays an important role in promoting the development of hepatic fibrogenesis. This study aimed to investigate the effect of angiotensin receptor blockade (irbesartan) on chronic CCL4 induced liver fibrosis and portal hypertension in rats. Moreover, to explore the possible mechanism (s) of action focusing on the role of the oxidative stress and inflammatory markers.
Forty five adult male albino rats were divided into three groups: group I fed standard diet and served as normal control group (CN), group II (non-treated control group), rats received CCL4 (1 ml/kg body weight i.p) with olive oil [1:1] twice a week for 4 weeks, group III received irbesartan (50mg/kg, daily p.o) immediately after the CCL4 injection for 4 weeks days to be used as treated group.
Results showed that irbesartan could significantly alleviate liver injury, as indicated by decreasing levels of ALT, AST, and TNF-α induced by CCL4. Moreover, irbesartan could effectively inhibit collagen deposition and reduce the pathological tissue damage. Finally, irbesartan significantly ameliorated the liver hemodynamic as evidenced by decreased portal hypertension and increased hepatic blood flow. Research on possible mechanism of these actions showed that irbesartan was markedly able to reduce lipid peroxidation.
Conclusion: irbesartan is effective in attenuating hepatic injury, portal hypertension and fibrosis in the CCl4 model in rats, through a suppression of oxidative stress and inflammatory markers. Thus, it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.
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