Acute inhibition of lymphatic cholesterol transport in rat intestine by SCH 58053.
To clarify the pharmacological mechanism of ezetimibe, SCH 58053, an analog of ezetimibe, was intraduodenally administered to lymph-fistula rats, and its effect on lymphatic lipid transport in the intestine was monitored. SCH 58053, 5.0 mg/kg body weight, was administered one hour before a 5-hour infusion of a lipid emulsion containing 40 micromol/h of triolein and 2.74 micromol/h of cholesterol (Experiment 1) or co-administered at 5.0 mg/kg body weight/h with the lipid emulsion for 4 hours to rats that had been infused with the lipid emulsion alone for 3 hours (Experiment 2). SCH 58053 administration significantly inhibited lymphatic cholesterol transport, but not triglyceride transport, in both groups compared to control rats that did not receive SCH 58053. The ratio of free cholesterol to total cholesterol in the lymph of the treated rats was unchanged compared to the control rats. Thus, the results showed that SCH 58053 is a potent, rapid, and selective inhibitor of lymphatic cholesterol transport in the intestine.
Hayashi
Hiroshi
H
Department of Internal Medicine, Atami Hospital, International University of Health and Welfare, 13-1 Higashikaigan-cho, Atami, Shizuoka 412-0012, Japan. hhayashi@iuhw.ac.jp
Kanai
Setsuko
S
Yamada
Yoshihiko
Y
Tsushima
Motoo
M
Miyasaka
Kyoko
K
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D007422:Intestines / Q000502:physiology; D042601:Lymphatic Vessels / Q000187:drug effects*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D001384:Azetidines; C476729:SCH 58053; D013141:Spiro Compounds; D002784:Cholesterol