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Journal of Nutrition Vol. 101 No. 11 November 1971, pp. 1515-1523
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Specific Inhibition of Cholesterol Absorption in Sulfaguanidine-fed Rats1

J. F. Van Den Bosch, G. A. Janssen, H. Eyssen and H. Vanderhaeghe

University of Leuven, The Rega Institute for Medical Research, 10 Minderbroedersstraat, B-3000 Leuven, Belgium

The influence of sulfaguanidine on the absorption of cholesterol was studied in the rat. In rats fed a diet without added cholesterol, feeding of 1% sulfaguanidine for 2 weeks did not significantly affect the cholesterol concentrations in the serum and the liver. Conversely, sulfaguanidine inhibited the rise of cholesterol levels in serum and liver of rats fed a 1% cholesterol diet. In rats with a thoracic duct fistula, feeding of 1% sulfaguanidine had no influence on lymphatic output of endogenous cholesterol but markedly inhibited the uptake of exogenous cholesterol. These experiments demonstrated that sulfaguanidine primarily inhibited the absorption of cholesterol from the intestine. The inhibitory effect on cholesterol absorption did not seem to be mediated via an effect on bile salts since sulfaguanidine did not promote fecal bile salt excretion, did not disturb micelle formation and did not displace cholesterol from preformed mixed micelles. Esterification of cholesterol by pancreatic esterase in vitro was not inhibited by concentrations of up to 10 mg of sulfaguanidine per milliliter. The effect of sulfaguanidine on cholesterol was highly specific, and minor modifications of the molecule resulted in almost complete loss of the inhibitory effect on cholesterol absorption.

1 Supported by a grant from the "Fonds voor Kollektief Fundamenteel Onderzoek" and by the "Instituut voor Wetenschappelijk Onderzoek in Nijverheid en Landbouw."

Manuscript received 6 May 1971.




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