Bile salts modulate chronic ethanol-induced hepatotoxicity.
This study tested the hypothesis that chronic ethanol-induced injury in rats may be modified by the hydrophobicity of the bile acid pool. The supplementation to chronic ethanol feeding (28 days) with chenodeoxycholate, a hydrophobic bile salt, aggravated steatosis (accumulation of triacylglycerols and cholesterol esters), lipoperoxidation and cytolysis (expressed as elevations of activities of aspartate aminotransferase and glutamate dehydrogenase), while the addition of ursodeoxycholic acid, a hydrophilic bile salt, alleviated ethanol-induced hepatic alterations. Furthermore, our data show that ursodeoxycholic acid still exerts its beneficial effects in a model of more severe hepatic intoxication induced by the co-administration of ethanol and chenodeoxycholic acid. The hepato-protective effect observed appears to be independent of the choleretic properties of ursodeoxycholic acid and may be due partly to the capacity of the bile acid to preserve mitochondria.
Montet
Anne-Marie
AM
Laboratoire de Physiopathologie Hépatique, INSERM, 46 Boulevard de la Gaye, 13009 Marseille, France.
Oliva
Laurence
L
Beaugé
Françoise
F
Montet
Jean-Claude
JC
D000818:Animals; D001647:Bile Acids and Salts / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D000431:Ethanol; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D015227:Lipid Peroxidation; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D001647:Bile Acids and Salts; D008055:Lipids; D002635:Chenodeoxycholic Acid; D000431:Ethanol; D014580:Ursodeoxycholic Acid; D007770:L-Lactate Dehydrogenase