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Titolo:
TMP-153, A NOVEL ACAT INHIBITOR, LOWERS PLASMA-CHOLESTEROL THROUGH ITS HEPATIC ACTION IN GOLDEN-HAMSTERS
Autore:
SUGIYAMA Y; ODAKA H; ITOKAWA S; ISHIKAWA E; TOMARI Y; IKEDA H;
Indirizzi:
TAKEDA CHEM IND LTD,DIV PHARMACEUT RES,PHARMACEUT RES LABS 2,YODOGAWAKU,2-17-85 JUSOHONMACHI OSAKA 532 JAPAN
Titolo Testata:
Atherosclerosis
fascicolo: 1, volume: 118, anno: 1995,
pagine: 145 - 153
SICI:
0021-9150(1995)118:1<145:TANAIL>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOW-DENSITY LIPOPROTEIN; APO-B SECRETION; ACYL-COA; RAT; ACYLTRANSFERASE; TRIGLYCERIDE; ABSORPTION; RECEPTOR; CELLS;
Keywords:
ACAT INHIBITOR; GOLDEN HAMSTER; PLASMA CHOLESTEROL; CHOLESTEROL ABSORPTION; HEPATIC CHOLESTEROL SECRETION; LDL CLEARANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
Y. Sugiyama et al., "TMP-153, A NOVEL ACAT INHIBITOR, LOWERS PLASMA-CHOLESTEROL THROUGH ITS HEPATIC ACTION IN GOLDEN-HAMSTERS", Atherosclerosis, 118(1), 1995, pp. 145-153

Abstract

The mechanism of the hypocholesterolemic action of N-[4-(2- )-6,7-dimelhyl-3-quinolyl]-N'-(2,4-difluorophenyl) urea (TMP-153), a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was studied in Golden hamsters. TMP-153 (0.5-1.5 mg/kg) dose-dependently reduced plasma total- and low density lipoprotein (LDL)-cholesterol without affectinghigh density lipoprotein (HDL)-cholesterol. TMP-153 markedly reduced the cholesterol influx into the plasma upon intravenous injection of Triton WR-1339. The compound also decreased cholesterol absorption calculated from dietary intake, biliary secretion and the absorption co-efficient. Hepatic cholesterol secretion was calculated by substracting the cholesterol absorption from the cholesterol influx. In hamsters, the liver accounted for 92% of the cholesterol influx with the remaining 8% coming from the intestine, and both were markedly decreased by TMP-153, Thus, it is likely that TMP-153 lowers plasma cholesterol through its hepatic action. In the liver, the compound significantly reduced the unesterified cholesterol content in addition to markedly reducing the content of esterified cholesterol. In accordance with this reduction, the half-life time of [I-125]-LDL was significantly shortened bythe compound, suggesting an increase in LDL receptors. However, the hepatic cholesterogenesis from [C-14]acetate was decreased by TMP-153 treatment. This effect seems to be secondary, since the compound did not inhibit cholesterogenesis from [C-14]acetate in HepG2 cells. From the data described above, the contribution of hepatic secretion and intestinal absorption of cholesterol to the plasma cholesterol level in Golden hamsters are discussed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 09:27:50