Effect of ursodeoxycholic acid on prostaglandin metabolism and microsomal membranes in alcoholic fatty liver.
The aim of the present study was to evaluate the effect of ursodeoxycholic acid (UDCA) on prostaglandin and fatty acid metabolism and the possible relation of these substances to the development of alcoholic fatty liver in rats. The effects of UDCA (40 mg/kg/day, 30 days) were studied in rats pair-fed a high-fat diet (52% of calories as fat) with daily ethanol (4 g/kg/day, 30 days) intragastric intubation. The livers of ethanol-treated animals were characterized by fatty dystrophy. Liver triglyceride and cholesterol ester contents and the activities of serum marker enzymes, alanine aminotransferase and gamma-glutamyltransferase, were significantly increased. Ethanol enhanced phosphoinositol and sphingomyelin content in liver microsomes and lowered prostaglandin E(2) (PGE(2)) concentration in the liver. An increase in the percentage of monoenoic fatty acids and a decrease in the n-6 acid family in liver phospholipids, linoleoyl-CoA desaturase, and PGE(2) synthase activities in liver microsomes were observed in ethanol-treated rats. Treatment with UDCA improved liver morphologic characteristics, decreased triglyceride and cholesterol ester contents, increased the PGE(2) level, and normalized linoleoyl-CoA desaturase and PGE(2) synthase activities, as well as phospholipid and fatty acid patterns in the liver. The activities of the serum marker enzymes were decreased in the ethanol- and UDCA-treated group. Ursodeoxycholic acid lowered the viscosity of the microsomal membrane, as assessed by both fluorescence probe techniques and the saturated/unsaturated fatty acid ratio. We propose that the hepatoprotective effect of UDCA in alcoholic fatty liver is related to the stabilization of microsomal membranes, the prevention of a decrease in essential fatty acids and PGE(2) in the liver, and, probably, an improvement in biochemical processes controlled by PGE(2).
Lukivskaya
O Y
OY
Institute of Biochemistry, National Academy of Sciences, 230017 Grodno, Belarus.
Maskevich
A A
AA
Buko
V U
VU
D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000378:metabolism* / Q000517:prevention & control; D007425:Intracellular Membranes / Q000737:chemistry / Q000187:drug effects*; D050356:Lipid Metabolism; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014580:Ursodeoxycholic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D014783:Viscosity / Q000187:drug effects
D002492:Central Nervous System Depressants; D002756:Cholagogues and Choleretics; D005227:Fatty Acids; D000431:Ethanol; D014580:Ursodeoxycholic Acid; D015232:Dinoprostone