The ACAT inhibitor HL-004 inhibits cholesterol absorption and lowers serum cholesterol in rats.
1. HL-004 decreased absorption of cholesteryl ester from the intestine into the lymph in a rat lymph-fistula model. 2. HL-004 reduced serum cholesterol level in acute cholesterol-fed rats. 3. HL-004 simultaneously decreased hepatic cholesteryl ester content and increased free cholesterol in cholesterol-fed rats. 4. These findings suggest that: (1) the hypocholesterolemic effect of HL-004 is principally due to inhibition of cholesterol absorption via inhibition of ACAT in the intestine; and (2) changes in hepatic cholesterol metabolism due to direct inhibition by HL-004 of hepatic ACAT may account in part for reduction of serum cholesterol level by HL-004.
Asami
Y
Y
Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Saitama, Japan. S10960@ccm.taisho.co.jp
Kondo
Y
Y
Murakami
S
S
Araki
H
H
Tsuchida
K
K
Higuchi
S
S
D000042:Absorption; D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005402:Fistula; D008099:Liver / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000083:Acetanilides; D000924:Anticholesteremic Agents; C092284:HL 004; D002784:Cholesterol; D002785:Sterol O-Acyltransferase