S‐adenosyl‐L‐methionine prevents and reverses erythrocyte membrane alterations in cirrhosis

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Abstract
Transmethylation is an important means of altering the biological activity of a wide variety of compounds. In human and experimental CCI4-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 Ca2+-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 CCI4-cirrhotic rats. Male Wistar rats were used in these experiments. In group 1, cirrhosis was induced by i.p. administration of CCI4. Animals of group 2 received, in addition to CCI4, three daily doses of SAM (20 mg kg−1, i.m.). Group 3 consisted of cirrhotic animals that, after 8 weeks of CCI4 treatment, received SAM (20 mg kg−1, i.m., three times daily) for 4 weeks without discontinuation of CCI4. 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 Ca2+ -ATPase activities were both significantly decreased (twofold) in the CCI4-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 Ca2+-ATPase activity was completely restored. CCI4 increased the CH/PL ratio; however, this alteration was not observed in the group treated with CCI4+ SAM simultaneously and was completely reversed in group 4. Since the increase in the membrane CH/PL ratio decreases the membrane fluidity and thus changes the enzyme activity, two mechanisms by which SAM preserves the ATPase activity in cirrhotic rats could be by preventing the increase in the CH/PL ratio and by methylation of phospholipids.

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