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-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-2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 mu mol/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: 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-2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.

17 Beta-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell cultures / M., Ricchi; Bertolotti, Marco; C., Anzivino; Carulli, Lucia; I., Canedi; Ml, Bormioli; Tiozzo, Roberta; Croce, Maria Antonietta; A., Lonardo; N., Carulli; P., Loria. - In: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY. - ISSN 0815-9319. - STAMPA. - 21:5(2006), pp. 894-901. [10.1111/j.1440-1746.2006.04144.x]

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

BERTOLOTTI, Marco;CARULLI, Lucia;TIOZZO, Roberta;CROCE, Maria Antonietta;
2006

Abstract

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-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-2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 mu mol/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: 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-2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification.
2006
21
5
894
901
17 Beta-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell cultures / M., Ricchi; Bertolotti, Marco; C., Anzivino; Carulli, Lucia; I., Canedi; Ml, Bormioli; Tiozzo, Roberta; Croce, Maria Antonietta; A., Lonardo; N., Carulli; P., Loria. - In: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY. - ISSN 0815-9319. - STAMPA. - 21:5(2006), pp. 894-901. [10.1111/j.1440-1746.2006.04144.x]
M., Ricchi; Bertolotti, Marco; C., Anzivino; Carulli, Lucia; I., Canedi; Ml, Bormioli; Tiozzo, Roberta; Croce, Maria Antonietta; A., Lonardo; N., Caru...espandi
File in questo prodotto:
File Dimensione Formato  
ricchi-j gstr hep.pdf

Solo gestori archivio

Tipologia: Versione pubblicata dall'editore
Dimensione 457.89 kB
Formato Adobe PDF
457.89 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/611723
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact