Bilirubin inhibits bile acid induced apoptosis in rat hepatocytes |
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Authors: | Granato A Gores G Vilei M T Tolando R Ferraresso C Muraca M |
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Affiliation: | Clinica Medica 1, University of Padova, Italy. |
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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 micromol/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. |
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