High Volume Screening Procedures for Hypobetalipoproteinemic Activity in Rats
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 clofibrate, lifibrate, nicotinic acid, probucol, triparanol, lentysine, D-thyroxine or the estrogens estrone and diethylstilbestrol.
KeywordsEstrogen Heparin Folic Acid Choline Fibrinogen
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- 1.Levy, R.S. and C.E. Day. 1970. Low density lipoprotein structure and its relation to atherogenesis. In: Atherosclerosis: Proceedings of the Second International Symposium. Ed. by R.V. Jones, Springer-Verlag, New York, pp. 186–189.Google Scholar
- 2.Day, C.E. and R.S. Levy. 1975. Control of the precipitation reaction between low density lipoproteins and polyions. Artery 1:150–164.Google Scholar
- 3.Alexander, C. and C.E. Day. 1973. Distribution of serum lipoproteins of selected vertebrates. Comp. Biochem. Physiol. 46B:295–312.Google Scholar
- 4.Day, C.E., B. Barker, and W.W. Stafford. 1974. Composition of very low density lipoproteins from cholesterol fed animals. Comp. Biochem. Physiol. 49B:501–505.Google Scholar
- 5.Day, C.E., P.E. Schurr, W.E. Heyd, and D. Lednicer. 1976. Biological activity of a hypobetalipoproteinemic agent. In: Atherosclerosis Drug Discovery Ed. by C.E. Day, Plenum Press, New York, pp. 231–249.Google Scholar
- 6.Block, W.D., K.J. Jarrett Jr., and J.B. Levine. 1965. Use of a single color reagent to improve the automated determination of serum total cholesterol. In: Automation in Analytical Chemistry, Ed. by L.T. Skeggs Jr., Mediad Inc., New York, pp. 345–347.Google Scholar
- 8.Snedecor, G.W., and W.G. Cochran. 1969. Statistical Methods. Iowa State University Press, Ames, Iowa, pp. 258–296.Google Scholar
- 10.Barnhart, J.W., V.A. Sefranka, and D.D. McIntosh. 1970. Hypocholesterolemic effect of 4,4′-(isopropylidenedithio)-bis (2,6-di-t-butylphenol) (Probucol). Am. J. Clin. Med. 23:1229–1233.Google Scholar
- 16.Cohen, B.M. 1970. Sodium dextrothyroxine. Clin. Med. 77:25–32.Google Scholar