17 Beta-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell cultures
| Autor: | Nicola Carulli, Amedeo Lonardo, Maria Antonietta Croce, Marco Bertolotti, Maria Luisa Bormioli, M. Ricchi, Irene Canedi, Claudia Anzivino, Paola Loria, Lucia Carulli, Roberta Tiozzo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Cell Survival
medicine.drug_class 17 Beta-estradiol Detergents Biology Cell Line chemistry.chemical_compound Cell Line Tumor Lactate dehydrogenase medicine Humans Viability assay cytotoxicity Cell damage TUNEL assay Estradiol Hepatology Bile acid Deoxycholic acid Gastroenterology medicine.disease Molecular biology Ursodeoxycholic acid Biochemistry chemistry Apoptosis Hepatocytes Hydrophobic and Hydrophilic Interactions Deoxycholic Acid medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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