Effects of MK-733, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on absorption and excretion of [ 3H]cholesterol in rabbits

• Published in: Biochimica et biophysica acta Vol. 963; no. 1; pp. 35 - 41
• Main Authors: Ishida, Fumiaki, Sato, Akiko, Iizuka, Yuri, Sawasaki, Yoshio, Aizawa, Atsushi, Kamei, Toshio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.11.1988; Elsevier; North-Holland
• Subjects: Administration, Oral; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cholesterol - pharmacokinetics; Cholesterol absorption; Cholesterol, Dietary - administration & dosage; Enzymes and enzyme inhibitors; Feces - analysis; Fundamental and applied biological sciences. Psychology; HMG-CoA reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic drug; Lovastatin - administration & dosage; Lovastatin - analogs & derivatives; Lovastatin - pharmacology; Male; Oxidoreductases; Rabbit; Rabbits; Simvastatin; Sitosterols - pharmacology; HMG-CoA reductase; Rabbit; CMC; HMG-CoA; Hypolipidemic drug; ACAT; Cholesterol absorption; AUC; Vertebrata; Excretion; Mammalia; Enzymatic activity; Radiolabelling; Diet; Enzyme; Enzyme inhibitor; Hydroxymethylglutaryl-CoA reductase; Metabolism; Cholesterol
• ISSN: 0005-2760; 0006-3002; 1879-145X; 1878-2434
• DOI: 10.1016/0005-2760(88)90335-9

Effects of MK-733 on the absorption and excretion of cholesterol in rabbits were examined using [ 3H]cholesterol. The animals were divided into six groups; three groups were fed a normal diet, and the other groups a cholesterol diet. MK-733 was administered orally as a single dose of 10 mg/kg on day 8, or multiple doses of 10 mg/kg once a day for 14 days. On the 8th day, [ 3H]cholesterol was given orally to each animal. In the groups fed a normal diet, single and consecutive administration of MK-733 did not affect the absorption and excretion of [ 3H]cholesterol. In the cholesterol-fed groups, however, single administration of MK-733 decreased the serum 3H radioactivity slightly, but did not affect the fecal excretion of [ 3H]cholesterol. However, the consecutive treatment with MK-733 clearly reduced the serum 3H radioactivity. The cumulative excretion of the fecal radioactivity of [ 3H]cholesterol in the MK-733 group (multiple) was higher than that in the control group. From these results, it is concluded that MK-733 inhibits the absorption of cholesterol from the gastrointestinal wall in cholesterol-fed rabbits.