Antioxidant mechanism of hepatoprotection by ursodeoxycholic acid in experimental alcoholic steatohepatitis.
OBJECTIVE
The aim of this study was to evaluate the role of an antioxidant factor in the hepatoprotective effect of ursodeoxycholic acid (UDCA) in rat alcoholic steatohepatitis.


METHODS
The effects of UDCA (40 mg/kg, i.g., 30 days) were studied using rats fed on a high-fat diet (52% calories as fat) and administered with ethanol via intragastric intubation (4 g/kg daily, 30 days).


RESULTS
The livers of ethanol-treated animals were characterized by fatty dystrophy. The relative liver weight and the square of the sudanophylic area as well as the liver triglyceride content and the activity of the serum marker enzymes, aspartate aminotransferase and gamma-glutamyltransferase, were significantly increased. Elevated superoxide dismutase activity as well as increased contents of lipid peroxidation products (hydroxyalkenals, malone dialdehyde, etc.) and lucigenin-enhanced microsomal chemiluminescence were observed in the liver of ethanol-treated rats and the liver reduced glutathione content was decreased. An increase in monoenoic fatty acids, a decrease of the n-6 acid family and an enhancement of microsomal membrane viscosity were found in the liver of these animals. An elevation of the total cytochrome P-450 content and the activity of amidopyrine-N-demethylase were shown in liver microsomes of the ethanol-treated group. The UDCA treatment improved the liver morphology, decreased serum marker enzyme activities, liver triglyceride content and normalized all the indices of oxidative stress. UDCA lowered the viscosity of the microsomal membrane, as assessed by both the fluorescence probe techniques and the saturated/unsaturated fatty acid ratio. The microsomal cytochrome P-450 content and amidopyrine-N-demethylase activity were normalized in UDCA-treated rats.


CONCLUSIONS
We can conclude that the hepatoprotective effect of UDCA stipulated by its antioxidant properties is indeed the factor enabling UDCA to control metabolic processes by changing the properties of liver membranes and membranous proteins.
Lukivskaya
O
O
Department of Experimental Hepatology, Institute of Biochemistry, National Academy of Sciences, Grodno, Belarus.
Zavodnik
L
L
Knas
M
M
Buko
V
V
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005227:Fatty Acids / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000975:Antioxidants; D002756:Cholagogues and Choleretics; D004041:Dietary Fats; D005227:Fatty Acids; D014280:Triglycerides; D000431:Ethanol; D014580:Ursodeoxycholic Acid; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D005978:Glutathione