Characterization of membrane fraction lipid composition and function of cirrhotic rat liver. Role of S-adenosyl-L-methionine.
The effect of S-adenosyl-L-methionine (SAM) administration on the lipid composition of the membrane fraction obtained from livers of cirrhotic rats was studied. Four groups of animals were used: group 1 received CCl4 for 8 weeks to induce cirrhosis. Animals in group 2 received 3 daily i.m. injections of SAM 20 mg/kg in addition to CCl4. Groups 3 and 4 were control groups of SAM and vehicles. Seventy-two h after the end of treatment all animals were killed and livers were studied to measure glycogen, cAMP contents and to isolate membrane fractions. The membrane activity of Na+,K(+)- and Ca(2+)-ATPases was measured and the lipid content was analyzed in extracts. Phospholipids were determined by thin-layer chromatography and fatty acids by gas chromatography. Chronic CCl4 treatment led to increases in cholesterol and in the cholesterol/phospholipid ratio. Analysis of phospholipids revealed an increase in phosphatidylserines. Saturated fatty acids increased, while unsaturated decreased significantly. The CCl4-treated group showed a decrease in glycogen and an increase in cAMP contents. Na+,K(+)- and Ca(2+)-ATPases activity were highly reduced in cirrhotic membranes. In the group receiving CCl4 + SAM the lipid composition and the function of liver membrane fraction showed no difference compared to normal controls, except for fatty acid composition which was similar to concentrations in the CCl4-treated group. Glycogen depletion was only partially prevented whereas cAMP levels were normalized in the CCl4 + SAM group. Our results showed that membrane lipid alterations were accompanied by changes in the activity of enzymes embedded in the membrane fraction derived from CCl4-cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Muriel
P
P
Departamento de Farmacología y Toxicología, CINVESTAV-IPN, México.
Mourelle
M
M
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002251:Carbon Tetrachloride / Q000494:pharmacology; D027682:Cation Transport Proteins; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D002784:Cholesterol / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D008099:Liver / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology* / Q000503:physiopathology; D008112:Liver Glycogen / Q000032:analysis; D008297:Male; D008563:Membrane Lipids / Q000032:analysis*; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000494:pharmacology*
D027682:Cation Transport Proteins; D008112:Liver Glycogen; D008563:Membrane Lipids; D010743:Phospholipids; D012436:S-Adenosylmethionine; D002784:Cholesterol; D002251:Carbon Tetrachloride; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; C022761:potassium transporting ATPase; C021838:sodium-translocating ATPase; D000252:Calcium-Transporting ATPases