Evaluation of the lipid-lowering activity of AY-25,712 in rats.
The effect of AY-25,712 (2-methyl-2-phenyl-3(2H)-furanone-5-carboxylic acid) on serum lipids, hepatic lipogenesis and biliary cholesterol was investigated in male rats. Based on one-week treatment, the minimal effective dose of AY-25,712 which lowered serum triglycerides was 1 mg/kg/day, and LDL-cholesterol, 5 mg/kg/day. Nicotinic acid produced a similar lipid-lowering profile albeit at 5 times higher doses. AY-25,712 at doses of 2 mg/kg/day and higher significantly increased the ratio of HDL to total cholesterol. Unlike clofibrate, AY-25,712 did not increase liver weight or liver mitochondrial alpha-glycerophosphate dehydrogenase, nor increase biliary cholesterol levels in rats fed a diet containing 2% cholesterol and 0.5% cholic acid. AY-25,712 lowered serum cholesterol, triglycerides and phospholipids in rats rendered hyperlipidemic with Triton WR-1339 and decreased the elevated serum triglycerides in streptozotocin-diabetic rats. [14C]Acetate incorporation into cholesterol by liver homogenate was suppressed in rats given AY-25,712 p.o. for 1 week. The results show that AY-25,712 is a potent LDL-cholesterol- and triglyceride-lowering agent in rats, and that its lipid-lowering profile differs from that of clofibrate but resembles that of nicotinic acid.
D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D002784:Cholesterol / Q000032:analysis / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005663:Furans / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006949:Hyperlipidemias / Q000139:chemically induced / Q000150:complications; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000032:analysis / Q000201:enzymology; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D005663:Furans; D000960:Hypolipidemic Agents; D008055:Lipids; D011092:Polyethylene Glycols; D002784:Cholesterol; C036804:acifran; D005993:Glycerolphosphate Dehydrogenase; C016811:tyloxapol