Combined effects of pravastatin and probucol on high-density lipoprotein apolipoprotein A-I kinetics in cholesterol-fed rabbits.
The combined effects of pravastatin and probucol on high- density lipoprotein (HDL) apolipoprotein (apo) A-I kinetics in cholesterol (Ch)-fed rabbits were investigated. Japanese White rabbits were treated with 0.15% pravastatin and 0.5% Ch (group 1) or 0.15% pravastatin plus 1% probucol and 0.5% Ch (group 2) for 2 months. After treatment, the serum total cholesterol levels in groups 1 and 2 had significantly (p < 0.01) increased (37.4 +/- 6.7 mg/dl vs 117.1 +/- 46.4 mg/dl, and 31.4 +/- 4.9 mg/dl vs 143.0 +/- 84.5 mg /dl, respectively). The serum HDL-cholesterol levels in both groups decreased (18.2 +/- 2.8 mg/dl, vs 16.2 +/- 3.7 mg/dl p < 0.01 for group 1; 18.2 +/- 1.9 mg/dl vs 15.5 +/- 4.5 mg/dl, ns for group 2). Apo A-I kinetics were assessed by injecting (125)I-labeled HDL intravenously into both groups of rabbits, and taking blood samples periodically for 6 days. Kinetic parameters calculated from apo A-I specific radioactivity decay curves showed that the apo A-I fractional catabolic rates in rabbits fed pravastatin and Ch (group 1) were significantly less than those in rabbits fed pravastatin plus probucol and Ch (group 2) (0.546 +/- 0.017 /day vs 0.730 +/- 0.126 /day, p < 0.05), while the synthetic rate of apo A-I was lower in group 2 than in group 1 (14.76 +/- 1.71 mg/kg per day vs 11.21 +/- 2.38 mg/kg per day, respectively, p < 0.01). These data indicate that pravastatin and probucol have different effects on HDL-apo A-I kinetics in a diet which includes cholesterol.
Saku
K
K
Department of Internal Medicine, Fukuoka University School of Medicine,Japan.
Liu
R
R
Jimi
S
S
Matsuo
K
K
Yamamoto
K
K
Yanagita
T
T
Arakawa
K
K
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000378:metabolism*; D004357:Drug Synergism; D007700:Kinetics; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology*; D011817:Rabbits
D016632:Apolipoprotein A-I; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D002784:Cholesterol; D017035:Pravastatin; D011341:Probucol