MDL 29311, an analog of probucol, decreases triglycerides in rats by increasing hepatic clearance of very-low-density lipoprotein.
MDL 29311 is an analog of probucol that shares probucol's antioxidant and antiatherogenic properties. When fed to rats as a 1% dietary admixture, MDL 29311 decreased triglyceride levels by 65% without affecting total or high-density lipoprotein (HDL) cholesterol levels. Under the same conditions, probucol decreased triglyceride levels by 23% and total cholesterol levels by 29% (with a corresponding decrease in HDL cholesterol level). MDL 29311 treatment did not affect the rate of triglyceride entry into the plasma. However, MDL 29311-treated rats cleared in vivo-labeled very-low-density lipoprotein (VLDL)-associated [3H]-triglyceride ([3H]-VLDL) over threefold faster than control rats. This increase in clearance led to increased levels of [3H]-lipid in liver and decreased [3H]-lipid in fat, muscle, diaphragm, and kidney of MDL 29311-treated rats 1.5 to 2.0 minutes after injection of [3H]-VLDL. MDL 29311 treatment had no effect on lipoprotein lipase (LPL) or hepatic triglyceride lipase (H-TGL) activities, or on plasma apolipoprotein (apo) C-II-dependent LPL activation. Intravenously injected [3H]-VLDL was allowed to circulate in MDL 29311-treated or control rats for 1 minute, and the undiluted plasma was then perfused through rat livers in a recirculating system. The [3H] in MDL 29311 plasma was cleared threefold faster (t1/2, 1.3 v 3.8 minutes) than the [3H] in control plasma by control livers. Conversely, the [3H] in control plasma was cleared slowly (t1/2 = 3.5 minutes) by the livers of MDL 29311-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheetz
M J
MJ
Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
Barnhart
R L
RL
Jackson
R L
RL
Robinson
K M
KM
D000818:Animals; D002784:Cholesterol / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008074:Lipoproteins / Q000097:blood; D008079:Lipoproteins, VLDL / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D011341:Probucol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C071022:MDL 29311; D002784:Cholesterol; D011341:Probucol