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Titolo:
HYPOLIPIDEMIC ACTION OF F-1394, AN ACYL-COA - CHOLESTEROL ACYLTRANSFERASE (ACAT) INHIBITOR, IN HIGH-FAT DIET FED BEAGLE DOGS
Autore:
KUSUNOKI J; ARAGANE K; KITAMINE T; YAMAURA T; OHNISHI H;
Indirizzi:
FUJIREBIO INC,PHARMACEUT RES LABS,51 KOMIYA CHO HACHIOJI TOKYO 192 JAPAN
Titolo Testata:
Yakugaku zasshi
fascicolo: 4, volume: 117, anno: 1997,
pagine: 233 - 241
SICI:
0031-6903(1997)117:4<233:HAOFAA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRIGLYCERIDE TRANSFER PROTEIN; APO-B SECRETION; MICROSOMAL TRIGLYCERIDE; DIABETIC RATS; HEPG2 CELLS; ABSORPTION; RABBITS; ATHEROSCLEROSIS; ESTERIFICATION; HAMSTERS;
Keywords:
ACYL-COA; CHOLESTEROL ACYLTRANSFERASE (ACAT); ACAT INHIBITOR; F-1394; HYPOLIPIDEMIC ACTION; DIET-INDUCED HYPERLIPIDEMIC DOG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
J. Kusunoki et al., "HYPOLIPIDEMIC ACTION OF F-1394, AN ACYL-COA - CHOLESTEROL ACYLTRANSFERASE (ACAT) INHIBITOR, IN HIGH-FAT DIET FED BEAGLE DOGS", Yakugaku zasshi, 117(4), 1997, pp. 233-241

Abstract

In the present study, we investigated the hypolipidemic effect of F-1394, a potent and selective inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), in dogs fed with a high-fat diet consisting of regular foods, 5% cholesterol and 16% fat. The serum cholesterol levels in dogs reached the steady-state 1 week after the start of feeding of a high-fat diet and were about 2-fold greater than those in normolipidemicdogs. Graded administration of the doses of F-1394 (1-30 mg/kg/d) to the dogs fed with a high-fat diet prevented the elevation of serum cholesterol levels. In the hyperlipidemic dogs fed with a high-fat diet for 14 d before the start of the administration of F-1394, the oral administration of F-1394 at a dose of 1, 3 or 10 mg/kg/d for 21 d reducedthe serum cholesterol levels in a dose-dependent manner. The estimated ID50 value was 7.2+/-0.3 mg/kg/dp. o. (12.1+/-0.5 mol/kg/dp. o.). F-1394 did not affect the body weight and no diarrhea was observed by the administration of F-1394. F-1394 at a dose of 10 mg/kg/d or more also significantly inhibited the increase of serum triglyceride levels 3 h after the feeding of high-fat diet. These results suggest that F-1394 inhibits the ACAT activity in the canine small intestine and, subsequently, the inhibition of ACAT activity contributes much to the prevention of cholesterol absorption via the gut, resulting in a decrease inserum cholesterol levels in the dogs fed with high-fat diet. Furthermore, F-1394 may also have an inhibitory effect on the triglyceride absorption via the gut, and the therapeutical use for postprandial hypertriglyceridemia is expected.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 19:22:32