Effects of niacin on biliary lipid output in the rat.
The mechanisms for the hypocholesterolaemic action of niacin (nicotinic acid) were examined in rats administered niacin at a dose of 400 mg/kg body wt/day for either 2 or 4 weeks. Another group of rats were administered diosgenin, an inhibitor of acyl-CoA:cholesterol acyltransferase, as a 1% (w/w) supplement in the diet for 7 days. Both agents produced small increases in bile flow rates (up to 40%) and mild hepatotoxicity evidenced by small increases in serum transaminase activities. Niacin treatment for 2 or 4 weeks lowered serum cholesterol concentrations by 13% or 29%, respectively, with the greatest decrease occurring in the low density lipoprotein fraction. This was accompanied by relatively large increases in biliary cholesterol output (114% and 130% after 2 and 4 weeks treatment, respectively) with smaller increases in the biliary output of phospholipid (18% and 45%) and bile acid (26% and 14%). Diosgenin treatment increased serum cholesterol by 29% and increased the biliary output of cholesterol, phospholipid and bile acid by 800%, 10% and 45%, respectively. Thus, both agents increased the cholesterol saturation of bile (100% by niacin, 500% by diosgenin). Cholesterol and phospholipid in fistula bile from control rats were present in lamellar and micellar forms. Niacin treatment did not alter the physical form of biliary lipids whilst diosgenin caused the appearance of vesicular lipid in fistula bile. Thus, increased biliary secretion of cholesterol explains, at least in part, the hypocholesterolaemic action of niacin. In addition, since aggregation of biliary vesicles is involved in cholesterol gallstone formation in humans, the non-appearance of vesicular material in fistula bile from niacin-treated rats may be of some importance.
Holland
R E
RE
School of Biomolecular Sciences, Liverpool John Moores University, U.K.
Rahman
K
K
Morris
A I
AI
Coleman
R
R
Billington
D
D
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004144:Diosgenin / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D008055:Lipids; D010743:Phospholipids; D009525:Niacin; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D004144:Diosgenin