Experimental hyper-beta-lipoproteinemia and its amelioration by a novel hypolipidemic agent.
Experimental models for hyper-beta-lipoproteinemia were established in rats and the effects of certain hypolipidemic drugs were studied with these models. In the hyperlipemia induced in rats by feeding a high cholesterol diet, Y-9738 [ethyl 2(4-chlorophenyl)-5-ethoxy-4-oxazoleacetate] produced a dose-dependent reduction of serum cholesterol: such hypolipidemic activity was estimated to be about 7 times as great as that of clofibrate. On the other hand, clofibrate induced hepatomegaly at 100 mg/kg, whereas Y-9738 did not at this dosage, which is about 10 times the effective dose. Hyperlipemia induced by high cholesterol and thiouracil was characterized by increased beta-lipoprotein (heparin-calcium and disc electrophoresis). In this model, Y-9738 showed a dose-dependent lowering effect on beta-lipoprotein cholesterol with a marked decrease in the beta/alpha lipoprotein ratio. A tendency was noted for alpha-lipoprotein to be increased. In contrast, clofibrate exerted no effect on this hyper-beta-lipoproteinemia. These results suggest that the above models may be of value in exploring hyper-beta-lipoproteinemia and that Y-9738 may be more useful than clofibrate in the therapy of hyperlipemia.
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002994:Clofibrate / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D010080:Oxazoles / Q000627:therapeutic use*; D011441:Propylthiouracil / Q000008:administration & dosage; D051381:Rats; D014280:Triglycerides / Q000097:blood
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D010080:Oxazoles; D014280:Triglycerides; C016920:ethyl 2-(4-chlorophenyl)-5-ethoxy-4-oxazoleacetate; D011441:Propylthiouracil; D002784:Cholesterol; D002994:Clofibrate