The hypolipidemic effects of 1-acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione in rodents.
1-Acetyl-4-phenyl-1,2,4-triazolidine,5-dione (APTD), a potent hypolipidemic agent, lowered both serum cholesterol and triglyceride levels in normo- and hyperlipidemic rats at 10 or 20 mg/kg/day. The agent effectively lowered VLDL-cholesterol (VLDL-C) and LDL-C content and raised HDL-C content in normal and hyperlipidemic rats treated from 4 to 8 weeks. Similar effects on the incorporation of cholesterol into the lipoprotein fractions were observed after drug treatment. Tissue lipids, e.g. cholesterol, were lowered, whereas fecal cholesterol levels were increased. APTD's primary targets were acyl CoA cholesterol acyl transferase (ACAT) for cholesterol ester synthesis and sn-glycerol-3-phosphate acyl transferase (GPAT) and phosphatidylate phosphohydrolase (PPH) for triglyceride synthesis.
Hall
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Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Simlot
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Day
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Wong
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ElSourady
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Izydore
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004032:Diet; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D006949:Hyperlipidemias / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014230:Triazoles; D014280:Triglycerides; C078499:1-acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione; D002784:Cholesterol