Effect of rioprostil and colchicine on CCl4-acute liver damage in rats. Relationship with plasma membrane lipids.
The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CCl4. The rats were sacrificed 24 h after CCl4. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CCl4 were equally prevented by the treatments with colchicine or rioprostil. CCl4 changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CCl4 and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins.
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D002251:Carbon Tetrachloride; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D003078:Colchicine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016630:Rioprostil; D005723:gamma-Glutamyltransferase / Q000097:blood
D008563:Membrane Lipids; D010743:Phospholipids; D011458:Prostaglandins E; D016630:Rioprostil; D002251:Carbon Tetrachloride; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin; D003078:Colchicine