Comparative Study on The Hepato-Protective Effect of Carvedilol and Nebivolol in Carbon Tetrachloride-Induced Liver Fibrosis in Normotensive and Hypertensive Albino Rats

Abstract

Background: Liver fibrosis is one of the main complications of chronic liver disease and is the main reason for increased mortality in affected patients. Fibrosis is characterized by excess deposition of extracellular matrix components including different collagens and non-collagenous proteins such as laminin, fibronectin and undulin.Objective: This study aimed to: (1) Evaluate the possible hepatoprotective effect of nebivolol and carvidelol on carbon tetrachloride (CCl4)-induced liver fibrosis. (2) Compare between hepatoprotective effect of nebivolol and carvidelol on CCl4-induced liver fibrosis on normotensive and hypertensive rats. Materials and Methods: This study was conducted on 110 male albino rats. Animals were obtained from the animal house of Faculty of Medicine, Assiut University. Their weight ranged between 160-200 grams each at the beginning of the experiment. Rats were housed in 11 groups with 10 rats each in clean capacious macrolane cages under standard laboratory conditions including good aerated room with suitable temperature (25 ± 5°C) and maintained at good light. Standard rodent food and water were available ad libitium. Results: Subcutaneous injection of CCl4 for 8 weeks caused hepatic pathological damage and significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, carvedilol and nebivolol decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline in liver tissues, and increased the activities of SOD and glutathione in liver tissue. Conclusion:The biochemical and histopathological changes induced by administration of CCl4 were improved under the effect of the used drugs in variable degrees. The most efficient drug was silymarin followed by carvedilol then nebivolol.