Studies on intestinal absorption, distribution and metabolism of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro[4-14C]stigmast-5-ene in mice.
A method for the analysis of 3 beta-chloro steroids by high-performance liquid chromatography is described. These compounds are known to occur in commercial protein hydrolysates. The gastro-intestinal absorption, distribution and metabolism of chlorinated steroids were studied after their intragastric application to mice. At 2 hr after stomach intubation of 3 beta-chloro[4-14C]cholest-5-ene and 3 beta-chloro-[4-14C]stigmast-5-ene, large proportions of radioactivity had passed through the small intestine and were found to be concentrated in the contents of the caecum and colon. Very small amounts of 3 beta-chlorocholest-5-ene were absorbed by the intestinal mucosa and distributed to organs and tissues outside the alimentary canal, whereas intestinal permeability of 3 beta-chlorostigmast-5-ene was negligible. After administration of labelled 3 beta-chlorocholest-5-ene, the highest value of radioactivity, 120 Bq/g tissue, outside the intestinal tract was detected in liver. Altogether, less than 0.5% of the total radioactivity applied to the animals was found to be transported through the intestinal wall and less than 0.5% of the total radioactivity was detected in various metabolites. In general, 3 beta-chlorostigmast-5-ene was transported in smaller proportions and metabolized to a lesser extent than the corresponding cholesterol derivative. Moreover, metabolites of the two radioactive substrates formed by enzymatic attack of enteric micro-organisms were not detected in the contents of the caecum and colon. It appears that 3 beta-chlorinated steroids are fairly stable products that are metabolized poorly both by the cells of the intestinal mucosa and by enteric micro-organisms of mice.
Weber
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Bundesanstalt für Fettforschung, H.P. Kaufmann-Institut, Münster, Federal Republic of Germany.
D000818:Animals; D002782:Cholestenes / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005243:Feces / Q000032:analysis; D005260:Female; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal; D008055:Lipids / Q000032:analysis; D051379:Mice; D012855:Sitosterols; D013025:Glycine max / Q000032:analysis; D013258:Steroids, Chlorinated / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002782:Cholestenes; D008055:Lipids; D012855:Sitosterols; D013258:Steroids, Chlorinated; C060067:3-chlorostigmast-5-ene; C060066:3-chlorocholest-5-ene