Contrasting patterns of selenium excretion by female CD rats treated with chemically related chemopreventive organic selenocyanate compounds.
We previously demonstrated that while both benzyl selenocyanate (BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) have high efficacy as cancer chemopreventive agents in several animal tumor models, p-XSC is less toxic. Using atomic absorption spectrophotometry, we compared the urinary and fecal excretion of total selenium derived from p-XSC and BSC in female CD rats. The results indicate that there exist distinct differences in the selenium excretion patterns when these compounds are administered orally, but not when they are administered i.p. In terms of the percent dose, the total selenium excreted in the 5 days following equimolar dosing (50 mumol/kg) of p-XSC or BSC, respectively, was as follows: after gavage, 68% or 3% in the feces and 6% or 18% in the urine; after i.p. administration, 9% or 4% in feces and 16% or 20% in urine. These results indicate that while most of the BSC administered orally is absorbed in the gastrointestinal tract, most of the p-XSC given the same way is not absorbed. This difference would account for the significantly lower tissue levels of selenium derived from orally administered p-XSC compared to BSC, and accounts, in part, for the lower oral toxicity of p-XSC compared to BSC. Subsequent studies employing o- and m-XSC, isomers of p-XSC, demonstrate that the excretion patterns of selenium are significantly different, depending on the position of substitution. In vitro studies suggest that the differences among BSC and the three XSC isomers with regard to absorption is probably due to different extent of binding to components of the gut contents. The results of these studies are useful for the future design of less toxic and more effective chemopreventive organic seleno-cyanates.
Sohni
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Division of Biochemical Pharmacology, American Health Foundation, Valhalla, NY 10595, USA.
Li
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Surace
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el-Bayoumy
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Upadhyaya
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Fiala
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics*; D003485:Cyanates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D007408:Intestinal Absorption; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D012643:Selenium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D016588:Anticarcinogenic Agents; D003485:Cyanates; D016566:Organoselenium Compounds; C054108:benzyl selenocyanate; C074153:1,4-phenylenebis(methylene)selenocyanate; D012643:Selenium