Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in the human Hep G2 cell line.
OBJECTIVE
Taurodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) exert a protective effect in chronic cholestasis. This study reports the effect of TUDCA and UDCA on an in vitro model for ethanol-induced liver damage.


METHODS
Hep G2 cells were incubated for 24 hours with 80 mmol/L ethanol in the presence or absence of 50 mumol/L TUDCA or UDCA. Cells were also pretreated with 80 mmol/L EtOH and then exposed to 50 mumol/L bile acids. Cytotoxicity was assessed by the metabolism of formazan (3-(4,5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and sodium 3,3'-(phenylamino) carbonyl-3,4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrase and by the release into the culture medium of different enzymes (aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transferase, and lactate dehydrogenase).


RESULTS
The incubation of Hep G2 with EtOH significantly (P < 0.001) increased cytotoxicity. Both TUDCA or UDCA reduced cytoxicity to a similar extent (P < 0.001). Cells pretreated with EtOH and then added with TUDCA or UDCA responded differently because TUDCA was significantly more effective (P < 0.05) than an equimolar dose of UDCA in reversing the damage. Electron microscopic examination revealed that TUDCA and UDCA were both able to prevent mitochondrial damage and to reduce steatosis induced by EtOH.


CONCLUSIONS
Low doses of TUDCA and UDCA protect Hep G2 cells from EtOH-induced cytotoxicity. However, TUDCA seems to be more effective than UDCA in reversing the damage.
Neuman
M G
MG
Division of Clinical Pharmacology, Sunnybrook Health Science Center, Toronto, Ontario, Canada.
Cameron
R G
RG
Shear
N H
NH
Bellentani
S
S
Tiribelli
C
C
D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008928:Mitochondria / Q000648:ultrastructure; D008954:Models, Biological; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid