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Dose-Response Relations in Urinary Excretion of Trimethylselenonium in the Rat¹

Steven H. Zeisel^*, Amy L. Ellis^*, X. F. Sun, Elizabeth A. Pomfret^*, Bill T. G. Ting and Morteza Janghorbani

^* Nutrient Metabolism Laboratory, Departments of Pathology and Pediatrics Stable Isotope Laboratory, Department of Pathology, Boston University School of Medicine, Boston, MA 02118

⁷⁵Se-labeled selenite was administered to fasting rats by orogastric intubation (1.5–3000 µg/kg body wt). Urine was collected and characterized for total radioactivity as well as for radiolabeled trimethylselenonium (TMSe). At lower doses of selenite (up to 500 µg/kg body wt), 30% of the administered dose was excreted. At higher doses of selenite, fractional urine excretion decreased as a function of the dose. The observed decrease in fractional urine excretion was not caused by changes in the absorption of the administered radiolable. There was a direct relationship between the amount of the administered dose of selenite (up to 1500 µg/kg body wt) and the proportion of urinary [⁷⁵Se] excreted as TMSe. Pretreatment with seleno compounds (10 or 100 µg Se/kg body wt as selenite, or selenomethionine) for 35 d before a challenge dose of [⁷⁵Se]selenite did not influence the excretion of total [⁷⁵Se] or of [⁷⁵Se]TMSe in urine. Ingestion of a choline-deficient diet, which should deplete the availability of methyl groups, did not have any effect on excretion of total [⁷⁵Se] or of [⁷⁵Se]TMSe in urine after a challenge dose of [⁷⁵Se]selenite (500 µg/kg body wt). The data presented here permit the following conclusions: 1) Production of TMSe is dose dependent, 2) production of TMSe from a single acute dose does not depend on the history of selenium intake and 3) rats fed a methyl-deficient diet are able to eliminate Se via formation of TMSe.

KEY WORDS: • trimethylselenonium • selenium • selenomethionine • selenite • urine • choline deficient

¹ This study was supported by grants from the National Institutes of Health (CA-38943, HD-16727) and from the U.S. Department of Agriculture (CRCR-1-1828).

Manuscript received 9 February 1987. Revision accepted 7 May 1987.