Metabolism of subtoxic levels of selenium in animals and humans.

Since high levels of selenium are used as cancer chemopreventive agents in animals and humans, a better understanding of the metabolism of subtoxic levels is desirable. Absorption from rat small intestine using in situ double perfusion, ligated intestinal segments, and brush border membrane vesicles (BBMV) was used to study selenium absorption. A level of 1.2 mM intraluminal selenite was required to inhibit 50 percent of the transepithelial transport of 3-0-methylglucose, indicating a high tolerance of the intestinal tract to selenium. The relative efficiency patterns for uptake of different selenocompounds during in vitro perfusion and in vivo ligated segments were identical with selenomethionine (SeMet) > selenate > selenite. In contrast, selenite was taken up most rapidly by BBMV, followed by SeMet and selenate in decreasing order. Ligated segments, double perfusion experiments, and uptake by BBMV indicated that selenium as selenodiglutathione or selenodicysteine was taken up faster than when present as selenite. Selenate and SeMet appeared in the vascular effluent largely unchanged, but selenite was metabolized extensively during absorption. Most of the selenium in plasma from subjects living in a high selenium area of China was associated with albumin, which is likely a result of high dietary intake of SeMet. Cracked fingernails and extensive hair loss were the symptoms of selenium toxicity in these individuals. Low adverse effect level of dietary (mean LOAEL) selenium was calculated to be about 1540 +/- 653 micrograms per day (or 28 micrograms/kg body weight) and the maximum safe dietary (mean NOAEL) selenium was calculated to be 819 +/- 126 micrograms per day (or 15 micrograms/kg body weight).