HEPATOLOGY: 17 beta -estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell cultures

Background:Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17 beta -estradiol (E sub(2)) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydro...

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Published in:Journal of gastroenterology and hepatology 2006-05, Vol.21 (5), p.894-901
Main Authors: Ricchi, Matteo, Bertolotti, Marco, Anzivino, Claudia, Carulli, Lucia, Canedi, Irene, Bormioli, Maria Luisa, Tiozzo, Roberta, Croce, Maria Antonietta, Lonardo, Amedeo, Carulli, Nicola, Loria, Paola
Format: Article
Language:English
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Summary:Background:Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17 beta -estradiol (E sub(2)) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. Methods:HepG2 cells were exposed for 24 h to DCA (350 mu mol-L). Cell viability, aspartate aminotransferase and lactate dehydrogenase activity and apoptosis were measured as indices of cell toxicity. The effect of DCA was compared to that observed using either a hydrophilic bile acid, ursodeoxycholic acid (UDCA; 100 mu mol-L), or E sub(2) at different concentrations (1 nmol-L, 10 nmol-L, 50 nmol-L and 50 mu mol-L) or mixtures of E sub(2)-DCA or UDCA-DCA. The same experiments were performed using WRL-68 cells that, at variance with HepG2, express a higher level of nuclear estrogen receptor. Results:High concentrations of E sub(2) and UDCA prevented DCA-induced decrease in cell viability, increase in enzyme activity and apoptosis evaluated both by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. In addition, DCA-related apoptosis, assessed by caspase activity, was also prevented by E sub(2) (P < 0.01) in physiological (1-10 nmol-L) doses. The cytoprotective effects of E sub(2) and UDCA was also observed in the WRL-68 cell line. Conclusions:17 beta -Estradiol prevents DCA-induced cell damage in HepG2 and WRL-68 cell lines to an extent comparable to UDCA. The hypothesis that the protective effect of E sub(2) may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.
ISSN:0815-9319
1440-1746
DOI:10.1111/j.1440-1746.2006.04144.x