S-adenosyl-L-methionine prevents and reverses erythrocyte membrane alterations in cirrhosis.
Transmethylation is an important means of altering the biological activity of a wide variety of compounds. In human and experimental CCl4-liver cirrhosis the intrahepatic content of S-adenosyl-L-methionine (SAM), an active methyl donor, and the SAM-transmethylase activity are markedly reduced. Previously, it has been reported that SAM administration preserves hepatocyte plasma membrane Na+/K(+)-ATPase and Ca(2+)-ATPase activities in cirrhotic rats. Therefore, the aim of this work was to study the effect of SAM administration on the membrane lipid composition and the ATPase activity on erythrocytes derived from CCl4-cirrhotic rats. Male Wistar rats were used in these experiments. In group 1, cirrhosis was induced by i.p. administration of CCl4. Animals of group 2 received, in addition to CCl4, three daily doses of SAM (20 mg kg-1, i.m.). Group 3 consisted of cirrhotic animals that, after 8 weeks of CCl4 treatment, received SAM (20 mg kg-1, i.m., three times daily) for 4 weeks without discontinuation of CCl4. Group 4 included animals treated with SAM alone. Seventy-two hours after the end of treatment the rats were anaesthetized, blood was collected by heart puncture and the erythrocyte plasma membranes were isolated. The Na+/K(+)- and (Ca2+ +Mg2+)-ATPase activities and the cholesterol (CH) and phospholipid (PL) contents were determined in the plasma membranes. The Na+/K(+)- and Ca(2+)-ATPase activities were both significantly decreased (twofold) in the CCl4-treated group as compared to controls. Administration of SAM completely prevented this fall in both ATPases. In group 4, the Na+/K(+)-ATPase activity was partially restored but the Ca(2+)-ATPase activity was completely restored.(ABSTRACT TRUNCATED AT 250 WORDS)
Departamento de Farmacologia y Toxicologia, Instituto Politecnico Nacional, Mexico, D. F.
P
P
Muriel
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000097:blood*; D008297:Male; D008563:Membrane Lipids / Q000097:blood; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood
D008563:Membrane Lipids; D010743:Phospholipids; D012436:S-Adenosylmethionine; D002784:Cholesterol; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase