Effects of dose on the methylation of selenium to monomethylselenol and trimethylselenonium ion in rats

Mechanisms and metabolic significance in rats of methylation to the reduced form of selenium (Se), i.e., selenide (Se2-), were studied by dose- and time-related experiments with injection of selenite. Urinary Se-metabolites were determined by HPLC using an inductively coupled argon plasma-mass spectrometer as an in-line detector (HPLC/ICP-MS method). Although only monomethylselenol (MMSe) has been detected in urine of normal rats even in those fed a Se-excess diet, the three types of Se-metabolites - MMSe, trimethylselenonium ion (TMSe), and inorganic Se, were detected in urine of Wistar rats injected with selenite (0, 0.1, 0.3, 0.5 and 1.0 mg Se/kg body weight) into the tail vein. The amount of the three Se-metabolites was plotted against the total urinary Se concentration and shown to change dose- and time-dependently. The monomethylated metabolite, i.e., MMSe, increased in urine rapidly at first and was slowly followed by linear dose-dependent ex cretion of the trimethylated metabolite, TMSe. The new methylation pathway of MMSe leading to TMSe was assumed to be induced or activated when the dose of Se exceeds the limit of the normal capacity for monomethylation. Progressive methylation reactions were suggested to be regulated enzymatically.