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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.

Transport of HDL cholesterol esters to the liver is not diminished by probucol treatment in rats.