Shunji Aono

Hypolipidemic action of a new aryloxy compound (S-8527) in rats

Abstract The effect of 1,1-bis[4′-(1′-carboxy-1′-methylpropoxy)-phenyl]cyclohexane (S-8527) on serum and liver lipids was studied in rats and compared with clofibrate. When rats were given a daily oral dose of 10 mg/kg or 30 mg/kg of S-8527 for 14 days, marked reduction of serum cholesterol and triglycerides was observed and the decreases were more pronounced than those in rats treated with 100 mg/kg or 300 mg/kg of clofibrate. There was no significant increase in liver weight, while clofibrate caused significant hepatomegaly. A similar hypolipidemic effect was observed when S-8527 was given mixed in the diet at concentrations of 0.01% or 0.03% and a more marked effect was noted in rats fed on a semisynthetic diet that contained sucrose as the only carbohydrate source. S-8527 lowered the hepatic triglyceride level but slightly raised the cholesterol level.

Effect of (−)N-[α-phenyl-β-(p-tolyl)ethyl] linoleamide on lipid levels in serum and liver in cholesterol-fed rats

The effect of (−)N-[α-phenyl-β-(p-tolyl) ethyl] linoleamide (PTLA) on lipid levels in serum and liver was compared with that of sitosterols in rats maintained on a diet supplemented with 1% of cholesterol, 0.5% of ox bile extracts, and 10% of hydrogenated coconut oil for 8 weeks. When PTLA was added to the diet at a level of 0.1%, the mean liver cholesterol level of male rats was reduced to 41% of the control and that of female rats was reduced to 19% of the control. In female rats, which showed higher cholesterol levels in serum and liver than male rats after cholesterol feeding, PTLA lowered the liver cholesterol level even at 0.0008% in the diet. Serum cholesterol was lowered by PTLA but not so markedly as liver cholesterol. The inhibition of cholesterol deposition in the liver suggests that the interference with cholesterol absorption is one of the main actions of PTLA. Sitosterols showed a similar pattern of lipid-lowering action, but the potency was far less than that of PTLA.

The effect of (−)N-[α-phenyl-β-(p-tolyl)ethyl] linoleamide on experimental atherosclerosis in rabbits

Optically active (−)N-[α-phenyl-β-(p-tolyl)ethyl] linoleamide (PTLA) was found to have a remarkable hypocholesterolaemic effect in rabbits. Administration of PTLA (5–10 mg/day/animal) significantly lowered serum and liver cholesterol and significantly prevented formation of aortic atheromatous changes in rabbits that had been given 1.6 g cholesterol daily.