Dietary cholesterol affects chenodeoxycholic acid action on biliary lipids.
Chenodeoxycholic acid (CDC) decreases biliary saturation and dissolves gallstones in one-half of the treated patients. Dietary cholesterol also affects biliary lipids and is a possible factor explaining unsuccessful CDC therapy. The aim of this investigation was to study the effect of high and low dietary cholesterol on the CDC-induced decrease of biliary saturation and activity of hepatic hydroxymethylglutaryl coenzyme A reductase (HMG-CoAR). Seventy two hamsters in six groups were fed for 1 month one of three diets: 0.8 mg of cholesterol per g of food, 2.4 mg of cholesterol per g, or cholesterol-free. On each diet hamsters received no CDC or CDC 30 mg per kg per day. When animals were killed, biliary lipids were determined and the activity of hepatic HMG-CoAR was assayed. CDC administration decreased the saturation index (SI)(P less than 0.01) in hamsters on the high cholesterol and standard diets but not on the cholesterol-free diet. The SI in CDC-treated hamsters on the high cholesterol (0.78 +/- 0.03) and cholesterol-free (0.68 +/- 0.02) diets were greater (P less than 0.02) than in CDC-treated hamsters on the standard diet (0.48 +/- 0.03). CDC decreased (P less than 0.01) HMG-CoA reductase activity on each diet. In comparison to HMG-CoAR activity (190 +/- 7.6 pmoles per mg per min) in CDC-treated hamsters on the standard diet, the activity in CDC-treated hamsters on the high cholesterol diet (176 +/- 5.8 pmoles per mg per min) was decreased ( less than 0.05), whereas the activity on the cholesterol-free diet (495 +/- 11.5 pmoles per mg per min) was greater (P less than 0.01). It is concluded that: (1) dietary cholesterol is necessary for optimum CDC inhibition of HMG-CoAR; (2) high cholesterol and cholesterol-free diets prevent maximum CDC decrease of the biliary saturation index; (3) dietary cholesterol alterations may therefore be one cause of the failure of CDC dissolution of gallstones.
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D002769:Cholelithiasis / Q000188:drug therapy; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D006224:Cricetinae; D004336:Drug Antagonism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D008647:Mesocricetus
D002791:Cholesterol, Dietary; D002635:Chenodeoxycholic Acid; D006903:Hydroxymethylglutaryl CoA Reductases