| Popis: |
The objectives of the present study were to evaluate the cancer chemopreventive activity of triphenylselenonium chloride and diphenylselenide and to investigate the pharmacology of these two compounds with respect to their tissue accumulation and excretion profile. Although both phenyl selenide derivatives are related to each other structurally, they differ substantially in their intrinsic chemical properties. Triphenylselenonium is positively charged and amphiphilic, while diphenylselenide is uncharged and lipophilic. With the use of either the DMBA- or MNU-induced mammary tumor model in rats, triphenylselenonium was found to have superior chemopreventive efficacy compared to diphenylselenide. Both reagents were present at 30 ppm Se in the diet. At the time of sacrifice (22 weeks post-carcinogen), triphenylselenonium produced only minimal accumulation of selenium in the liver, kidney, mammary gland and plasma. In contrast, diphenylselenide caused a 2- to 3-fold elevation in selenium concentration depending on the tissue examined. Thus even though diphenylselenide was able to increase total selenium in tissues, it was less active in cancer protection. Fecal excretion following a single oral dose of triphenylselenonium (equal to the amount consumed in 1 day by an animal fed a diet containing 30 ppm Se) was approximately 78% and 8% of the dose during the first and second day, respectively, suggesting that the bulk of the dose was not absorbed. With diphenylselenide, fecal excretion was about 6% and 30% of the dose during the first and second day, and about 20% of the dose was excreted in the urine in each of the 2 days. This observation suggests that a large proportion of the diphenylselenide dose was absorbed and that urinary excretion was a major route of elimination for diphenylselenide once it was absorbed. Further studies are needed to clarify the basis for the differential effects of these phenyl selenide derivatives. |
