ORAL ACETYLSALICYLIC-ACID INDUCES BILIARY CHOLESTEROL SECRETION IN THE RAT

Several agents can alter biliary cholesterol secretion, critical for c holesterol excretion and gallstone formation. Although salicylate effe cts on bile formation and gallstones have been studied, biliary lipid secretion has not been measured during oral aspirin treatment. We exam ined whether oral acetylsalicylic acid affects bile lipid secretion. T hree groups of young rats were fed chow for 3 wk. Two of the groups th en received aspirin at either 1.67 or 3.33 g/kg diet for 4 d. Serum, h epatic, and bile lipids were measured, as were enzymes of cholesterol synthesis and esterification. With oral aspirin, bile cholesterol secr etion increased by 42% and hepatic cholesteryl ester content decreased by 40%. Serum cholesterol and hepatic free cholesterol did not change . To evaluate mechanisms of the cholesterol hypersecretion, hypothyroi d animals fed low-fat or fish oil diets and repleted with triiodothyro nine were also studied. Aspirin stimulated cholesterol secretion to a degree similar to triiodothyronine. An additive response was seen in F ish oil-fed rats. Aspirin did not appear to have a primary action on 3 -hydroxy-3-methylglutaryl-CoA reductase or acyl CoA:cholesterol acyltr ansferase activities, and had no direct effect on esterification of ch olesterol by isolated hepatocytes. Aspirin may directly increase chole sterol transport into bile or have cell membrane effects which alter c holesterol transport. It remains to be determined whether the observed alterations in bile cholesterol secretion are specific to the rat or also apply to humans.