Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes
- 1Clinica Medica 1, University of Padova, Italy
- 2Division of Gastroenterology and Hepatology, Mayo Medical School, Clinic and Foundation, Rochester, Minnesota, USA
- 3GlaxoSmithKline Research Centre, Verona, Italy
- Correspondence to:
Dr M Muraca
Department of Medical and Surgical Sciences, University of Padova, Via Giustiniani, 2, I-35128 Padova, Italy; muracaunipd.it
- Accepted 25 June 2003
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.
- 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
