Effect of S-adenosylmethionine versus tauroursodeoxycholic acid on bile acid-induced apoptosis and cytolysis in rat hepatocytes

Eur J Clin Invest. 1998 Jul;28(7):577-83. doi: 10.1046/j.1365-2362.1998.00315.x.

Abstract

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.

Conclusion: 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.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Bile Acids and Salts / pharmacology*
  • Bile Acids and Salts / physiology
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Liver / cytology
  • Liver / drug effects*
  • Liver / physiology
  • Male
  • Rats
  • Rats, Wistar
  • S-Adenosylmethionine / pharmacology*
  • Taurochenodeoxycholic Acid / pharmacology*

Substances

  • Bile Acids and Salts
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • S-Adenosylmethionine