Effect of S-adenosylmethionine versus tauroursodeoxycholic acid on bile acid-induced apoptosis and cytolysis in rat hepatocytes.
BACKGROUND
S-adenosylmethionine (SAMe) increases survival in alcoholic liver cirrhosis and may have a beneficial effect in cholestatic liver disease. SAMe repletes glutathione stores and protects tissue from oxygen free radicals. The effect of SAMe on bile acid-induced apoptosis is unknown. In the present study the possible hepatoprotective effect of SAMe was evaluated and compared with that of tauroursodeoxycholic acid (TUDCA).


METHODS
Primary rat hepatocytes treated with glycochenodeoxycholic acid (GCDCA) were used as a model for cholestasis-induced hepatocellular damage, which served to study the effects of SAMe and TUDCA on bile acid-induced apoptosis and cytolysis.


RESULTS
SAMe reduced bile acid-induced apoptosis but did not prevent bile acid-induced cytolysis. Compared with SAMe, TUDCA was more efficient in reducing apoptosis due to toxic bile acids. The combination of SAMe and TUDCA had additive effects in reducing apoptosis.


CONCLUSIONS
The reduction in bile acid-induced apoptosis by SAMe may represent one of the factors responsible for its beneficial effects in the treatment of liver diseases.
Benz
C
C
Department of Medicine, University of Heidelberg, Germany.
Angermüller
S
S
Klöters-Plachky
P
P
Sauer
P
P
Stremmel
W
W
Stiehl
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000494:pharmacology* / Q000502:physiology; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D012436:S-Adenosylmethionine