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 17beta-estradiol (E2) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid.


METHODS
HepG2 cells were exposed for 24 h to DCA (350 micromol/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 micromol/L), or E2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 micromol/L) or mixtures of E2/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 E2 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 E2 (P < 0.01) in physiological (1-10 nmol/L) doses. The cytoprotective effects of E2 and UDCA was also observed in the WRL-68 cell line.


CONCLUSIONS
17Beta-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 E2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.
Ricchi
Matteo
M
Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Bertolotti
Marco
M
Anzivino
Claudia
C
Carulli
Lucia
L
Canedi
Irene
I
Bormioli
Maria Luisa
ML
Tiozzo
Roberta
R
Croce
Maria Antonietta
MA
Lonardo
Amedeo
A
Carulli
Nicola
N
Loria
Paola
P
D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003902:Detergents / Q000633:toxicity; D004958:Estradiol / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions
D003902:Detergents; D003840:Deoxycholic Acid; D004958:Estradiol