Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes

Granato, A.; Gores, G.; Vilei, M. T.; Tolando, R.; Ferraresso, C.; Muraca, M.
December 2003
Gut;Dec2003, Vol. 52 Issue 12, p1774
Academic Journal
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 (UCS) 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.


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