The Possible Hepatoprotective Effects of Azilsartan against Carbon Tetrachloride CCl4 - Induced Liver Fibrosis in Male Rats in Comparison with Silymarin: ''in vivo Study''

Hepatic fibrosis is a pathophysiological outcome of sustained wound healing response to chronic liver injury charecterized by excessive accumulation of extracellular matrix proteins. Progressive liver fibrosis can be caused by chronic infection of hepatitis B or C, alcohol abuse, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and other relatively conditions. Liver fibrosis, the subsequent cirrhosis represent a serious medical burden; yet, there is still a lack of approved methods or drugs to prevent or reverse liver fibrosis. Therefore, effective hepatic antifibrotic drugs are urgently needed. Aim of this study was to investigate the possible potential hepatoprotective effects of azilsartan in rats against carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Forty white male albino rats were utilized in this study. During such study liver fibrosis was induced by intraperitoneal (I.P) injection of CCl4 50% in olive oil 1ml/kg twice weekly for 6 consecutive weeks in. Azilsartan and silymarin were administered orally daily concurrently with I.P CCl4 in the treatment groups. Following the end of sixth week from induction and treatment period, all animals were weighed individually, then euthanised and their livers have been weighed to determine the relative liver weight percentage. Furthermore, a piece of each rat liver tissue was homogenized for determination of tissue malondialdehyde and reduced glutathione. Moreover, liver tissues slices were prepared to study necroinflammation degree, and collagen deposition (fibrosis stage) histopathologicaly. Ultimately, transforming growth factor TGF-β1, alpha smooth muscle actin, and hydroxyproline were all assessed for their immunohistochemistry expression levels in this study. The results revealed that intraperitoneal injection of CCl4 in olive oil in rats resulted in inflammation and fibrosis induction and so, increasing in relative liver weight. Such intraperitoneal injection leaded to increased tissue level of MDA, decreased GSH, and elevation in immunohistochemical expression of TGFβ1, alpha smooth muscle actin , and hydroxyproline as compared to normal control group. Finally, Oral administration of azilsartan and silymarin was significantly improved discussed parameters representing hepatoprotection.