No abstract

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.

No abstract

The hydrophilic bile salt ursodeoxycholate (UDC) improves cholestasis in several liver diseases and is in vitro an efficient membrane stabilizer. However, its action on chronic ethanol-induced liver damage is not established. We thus sought to determine the effect of UDC on chronic ethanol-induced steatosis and on liver plasma membrane fluidity in rats. Male rats were pair-fed liquid diets containing 36% of calories as ethanol (alcohol diet) or an isocaloric maltose-dextrin mixture (control diet). Four groups of 10 animals received, respectively, during 30 days: the control diet, the control diet + UDC (90 mg/kg/day), the alcohol diet, and the alcohol diet + UDC. Bile was collected for assessment of bile flow, biliary lipids, and individual bile salts. Liver lipid contents and lipid peroxidation were determined. Plasma membrane fluidity was assessed by fluorescence polarization of various probes. Alcohol treatment caused a 4-fold increase in liver triacylglycerol and cholesterol ester levels. UDC supplementation significantly reduced these increases by 50% and 40%, respectively. UDC intake was associated with a marked decrease in alcohol-induced lipid peroxidation. Bile flow, bile salt, and phospholipid secretion were slightly increased by alcohol intake. The addition of UDC-enriched bile with tauroursodeoxycholate (38%) without significantly affecting the biliary parameters. Lastly, UDC treatment almost totally prevented the 20% increase in liver plasma membrane fluidity due to chronic alcohol intake. This study shows that UDC intake, concomitant with alcohol diet, exerts a clear-cut membrane protective effect that might alleviate ethanol-induced lipid disorders.