Evaluation of the lipid-lowering activity of AY-25,712 in rats

Atherosclerosis. 1982 Dec;45(3):267-79. doi: 10.1016/0021-9150(82)90228-3.

Abstract

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.

MeSH terms

  • Animals
  • Bile Acids and Salts / analysis
  • Cholesterol / analysis
  • Cholesterol / biosynthesis
  • Diabetes Mellitus, Experimental / complications
  • Furans / pharmacology*
  • Glycerolphosphate Dehydrogenase / metabolism
  • Hyperlipidemias / chemically induced
  • Hyperlipidemias / complications
  • Hypolipidemic Agents / pharmacology*
  • Lipids / analysis
  • Lipids / blood
  • Liver / analysis
  • Liver / enzymology
  • Male
  • Polyethylene Glycols / administration & dosage
  • Rats
  • Rats, Inbred Strains

Substances

  • Bile Acids and Salts
  • Furans
  • Hypolipidemic Agents
  • Lipids
  • Polyethylene Glycols
  • Cholesterol
  • acifran
  • Glycerolphosphate Dehydrogenase
  • tyloxapol