Protective effect of S-adenosyl-L-methionine against CCl4-induced hepatotoxicity in cultured hepatocytes.
Effect of S-adenosyl-L-methionine disulfate tosylate salt (SAMe-ST) and L-methionine (L-Met) on primary cultured rat hepatocytes were studied. In cultured hepatocytes treated with CCl4, SAMe-ST and L-Met suppressed the decrease in urea-nitrogen secretion as well as the leakages of GOT and GPT. The membrane-protective action of these two compounds was verified by the histological data. Failure of SAMe-ST to counteract CCl4-induced reduction of radioactive leucine incorporation into the trichloroacetic acid-insoluble materials in hepatocytes indicates that the observed effects of SAMe-ST or L-Met do not involve acceleration of protein synthesis. The present results indicate that SAMe-ST remarkably protects hepatocytes from CCl4-induced hepatotoxicity, probably by either changing the structure or compositions of membrane phospholipids or by modifying the interaction of CCl4 with the intracellular drug-metabolizing enzyme systems.
Tsuji
M
M
Department of Pharmacology, School of Medicine, Showa University, Tokyo, Japan.
Kodama
K
K
Oguchi
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D007930:Leucine / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000627:therapeutic use*
D012436:S-Adenosylmethionine; D008715:Methionine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007930:Leucine