Mechanism of the plasma cholesterol lowering effect of tazasubrate in rats: accelerated plasma cholesterol transport with increased liver lipoprotein receptor activity.
Tazasubrate (30 mg/kg/day) a new lipid lowering agent, chemically unrelated to fibrates, reduces plasma cholesterol in rats within 2-3 days to 50% of controls. During the early rapid decrease of plasma cholesterol, increased liver cholesterol concentrations are observed. These return to normal, once the new steady state of plasma cholesterol (at 50% of controls) has been reached. Radiotracer studies with 3H-cholesterol labelled plasma very low density lipoproteins are consistent with an accelerated plasma cholesterol turnover. Analysis of the binding to liver membranes of 125I labelled cholesterol rich very low density lipoproteins (beta-VLDL) shows a marked increase in the total binding (Bmax rising from 106 ng/mg of protein 378 ng/mg), without significant alterations in the receptor affinity.
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D015243:Cholesterol, VLDL; D005260:Female; D008074:Lipoproteins / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018110:Receptors, Lipoprotein; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D000924:Anticholesteremic Agents; D015243:Cholesterol, VLDL; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D013844:Thiazoles; C041008:tazasubrate; D002784:Cholesterol