High volume screening procedures for hypobetalipoproteinemic activity in rats.

ABSTRACT

We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol.