Transport of HDL cholesterol esters to the liver is not diminished by probucol treatment in rats.
This study examined the relation of decreased high density lipoprotein (HDL) levels in probucol-fed rats and the transport of HDL cholesterol esters (CEs) to the liver. HDLs from both control rats and rats fed 1% probucol for 3 weeks were doubly labeled in their CE and apolipoprotein A-I moieties with intracellularly trapped tracers and then intravenously injected into probucol-fed or control rats for determination of plasma decay kinetics and sites of tracer uptake. Results for HDL from control and probucol-fed rats were not different. The fractional catabolic rate (FCR) of plasma HDL CE was significantly increased by probucol feeding (23%) so that mass transport of HDL CE through the plasma compartment was not significantly different from that in control rats. The plasma FCR for apolipoprotein A-I did not change. Similarly, the FCR for uptake of HDL CE by the liver increased on probucol feeding (20%), resulting in a near-normal rate of HDL CE mass uptake, whereas the FCR for HDL particle uptake (measured by apolipoprotein A-I uptake) did not change. Thus, the maintenance of near-normal HDL CE uptake by the liver was exclusively due to increased selective uptake (32%). To the extent that hepatic uptake of HDL CE mediates reverse cholesterol transport, that process was not significantly compromised in rats fed 1% probucol.
Richard
B M
BM
Department of Medicine, University of California, San Diego, La Jolla 92093-0613.
Pfeuffer
M A
MA
Pittman
R C
RC
D000818:Animals; D016632:Apolipoprotein A-I / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D002788:Cholesterol Esters / Q000737:chemistry / Q000493:pharmacokinetics*; D008076:Cholesterol, HDL / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D010316:Particle Size; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D011341:Probucol