Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes. Issue 12 (21st November 2003)

• Record Type: Journal Article
• Authors: Granato, A; Gores, G; Vilei, M T; Tolando, R; Ferraresso, C; Muraca, M
• Is Part Of: Gut. Volume 52:Issue 12(2003)
• Page Start: 1774
• Page End: 1778
• Publication Date: 2003-11-21
• Subjects: apoptosis -- bile acids -- bilirubin -- cholestasis -- rat hepatocytes; GCDC, glycochenodeoxycholate -- UCB, unconjugated bilirubin -- CB, conjugated bilirubin -- ROS, reactive oxygen species -- DAPI, diamidino-2-phenylindole dihydrochloride -- BSA, bovine serum albumin -- DCF, dichlorofluorescein -- LDH, lactate dehydrogenase -- GLDH, glutamate dehydrogenase -- AST, aspartate aminotransferase; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.52.12.1774
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background and aims: Hydrophobic bile acids contribute to hepatocellular injury in cholestasis and rapidly induce apoptosis in vitro; however, unlike Fas agonists, cholestasis does not cause extensive hepatocyte apoptosis. As antioxidants provide protection against bile acid induced liver injury, our premise was that bilirubin, a free radical scavenger with increased plasma levels in the presence of liver disease, could protect hepatocytes against bile acid induced apoptosis. Methods: Freshly isolated rat hepatocytes were incubated for four hours with 100 μmol/l glycochenodeoxycholate (GCDC) alone or with increasing concentrations of unconjugated (UCB) or conjugated (CB) bilirubin. Results: Both UCB and CB inhibited GCDC induced apoptosis in a dose dependent fashion and suppressed the generation of reactive oxygen species by hepatocytes. Conclusions: The antiapoptotic effect of bilirubin associated with its antioxidant properties indicates that hyperbilirubinaemia may have a protective role in liver disease.