The Role Of Apelin And Protamine Sulphate In Bile Duct Ligation Induced Liver Fibrosis In Rats

Abstract Purpose: This study was designed to investigate the effectiveness of protamine sulphate as an apelin receptor blocker on cholestatic liver fibrosis persuaded by common bile duct ligation (BDL) in experimental rats and examine some related mechanisms. Methods: Three groups of adult male Wistar rats were included: control (sham-operated), BDL and BDL+ protamine sulphate groups. All groups were examined after 4 weeks for serum apelin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), hepatic interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), glutathione peroxidase, (GPx) malondialdehyde (MDA), transforming growth factor-β (TGF-β) and hydroxyproline content and for extracted livers histopathological studies. Results: BDL significantly increased serum apelin, total bilirubin, AST, ALT, ALP, hepatic IL-6, TNF-α, MDA, TGF-β and hydroxyproline content, but it significantly reduced serum albumin level and hepatic GPx and SOD activities. Serum level of apelin significantly revealed positive correlations with TNF-α, MDA, TGF-β and hydroxyproline content. On the other hand, protamine sulphate significantly attenuated these changes, with no effect on either serum apelin or bilirubin levels, in treated group. It also improved the hepatic histopathological changes. Conclusion: Protamine sulphate, may be through its apelin receptor blockade, ameliorated cholestatic liver injury, inflammation, and fibrosis induced by BDL.