EFFECTS OF N-(4-METHYLBENZYLTHIOCARBONYL)-L-PHENYLALANINE (KF 1492), A NEW HYPOLIPIDEMIC DRUG, AND CLOFIBRATE ON LIPIDS METABOLISM

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The effects of N-(4-methylbenzylthiocarbonyl)-L-phenylalanine (KF 1492) on the intestinal lipid absorption, the biliary lipid composition and α-glycerophosphate dehydrogenase (GPD) activity have been investigated in rats in comparison with clofibrate. KF 1492 did not have inhibitory activity on intestinal absorption of cholesterol and triglyceride. In the KF 1492-treated group (100mg/kg, 8d), an increase of bile flow (25.9%) per g liver was observed. The increase of excretion of bile acids (29.9%), phospholipids (45.2%) and cholesterol (33.4%) due to the increase of bile flow was clearly observed but no significant change in the concentration of each lipid was observed. In clofibrate-treated group, the concentration of bile acids and cholesterol in bile was decreased and output of biliary phospholipids was increased. Approximately 5 to 10 times increase of GPD activity was observed in mitochondrial fraction of the KF 1492- or clofibrate-treated rats (0.25% (w/w) in rat chow, 3 weeks). Thus, the increased degradation and excretion of cholesterol to bile may explain the hypocholesterolemic activity of KF 1492.
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