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17β‐estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL‐68 cell cultures
Author(s) -
Ricchi Matteo,
Bertolotti Marco,
Anzivino Claudia,
Carulli Lucia,
Canedi Irene,
Bormioli Maria Luisa,
Tiozzo Roberta,
Croce Maria Antonietta,
Lonardo Amedeo,
Carulli Nicola,
Loria Paola
Publication year - 2006
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04144.x
Subject(s) - ursodeoxycholic acid , viability assay , apoptosis , lactate dehydrogenase , tunel assay , bile acid , deoxycholic acid , dapi , biochemistry , cytotoxicity , liver cell , microbiology and biotechnology , pharmacology , medicine , chemistry , in vitro , enzyme , biology
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 17β‐estradiol (E 2 ) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. Methods: HepG2 cells were exposed for 24 h to DCA (350 µmol/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 µmol/L), or E 2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 µmol/L) or mixtures of E 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 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 2 ( P < 0.01) in physiological (1–10 nmol/L) doses. The cytoprotective effects of E 2 and UDCA was also observed in the WRL‐68 cell line. Conclusions: 17β‐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 2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.