Katsuyuki Toki

The effect of N-(α-Methylbenzyl) linoleamide on experimental atherosclerosis in rabbits

Summary The effect of N-(α-methylbenzyl) linoleamide (MBLA) on experimental atherosclerosis in rabbits was investigated at various dose levels in comparison with those of N-cyclohexyl linoleamide (CHLA) and β-sitosterol. (1) MBLA and CHLA had marked lipid-lowering and anti-atherogenic effects, but MBLA was more effective than CHLA. (2) At the dose level of 800 mg/day, β-sitosterol lowered serum cholesterol, but less so than MBLA at 100 mg/day. (3) With daily administration of 400 mg of MBLA, elevation of serum cholesterol and development of aortic atherosclerosis were almost completely pre/ented in rabbits fed 1.6 g cholesterol daily. MBLA lowered serum cholesterol and exhibited an anti-atherogenic effect at the dose level of 25 mg/day.

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.

Metabolism of Linoleamides: I. Absorption, Excretion and Metabolism of N-(α-Methylbenzyl)linoleamide in Rat and Man

1. In urine of rats dosed with N-(alpha-methylbenzyl)linoleamide (MBLA), three dicarboxylic acid monoamides, N-(alpha-methylbenzyl)succinic acid monoamide, N-(alpha-methylbenzyl)glutaric acid monoamide and N-(alpha-methylbenzyl)adipic acid monoamide, were identified. Conjugated alpha-methylbenzylamine, hippuric acid and conjugates of the dicarboxylic acid monoamides were also found in the urine. N-(alpha-Methylbenzyl)succinic acid monoamide was the main metabolite in rats. 2. Biliary excretion of radioactivity was studied in rats, cannulated for collection of bile and duodenal infusion, after oral administration of N-(alpha-methylbenzyl)[1-14C]linoleamide. With constant duodenal infusion of bile, about 7% of the dose was excreted in the bile, while excretion of radioactivity was negligible without bile infusion. 3. The g.l.c. analysis of human urine after oral administration of MBLA revealed that two dicarboxylic acid monoamides were present and N-(alpha-methylbenzyl)succinic acid monoamide was the main metabolite. 4. MBLA was excreted unchanged in the faeces of men who received MBLA to the extent of about 53% dose in 3 days. 5. MBLA was not detected (less than 1 mug/ml) in the serum of a volunteer who had been taking an oral daily dose of 1500 mg of MBLA for 3 months.

Inhibition of cholesterol absorption by (−)N-[α-phenyl-β-(p-tolyl) ethyl] linoleamide in rats

The effect of (−)N-[α-phenyl-β-(p-tolyl)ethyl] linoleamide (PTLA) on intestinal absorption of cholesterol was studied in rats. Oral administration of 15 mg PTLA to rats resulted in a significant (P<0.05) decrease in the radioactivity in serum and liver 4 hr after administration of labeled cholesterol. The effect of PTLA was greater on the absorption of cholesteryl oleate as compared with free cholesterol. The rate of hydrolysis of cholesteryl oleate in mucosal homogenates of rat intestine was decreased with PTLA, suggesting that the inhibition of cholesterol absorption by PTLA is related to its effect on cholesteryl ester hydrolysis in the intestine.

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.