Some Possible Mechanisms of Interaction

Various proposals have been presented to explain the interaction of selenium with heavy metals. However, no single one appears to explain the mechanism of interaction with all heavy metals. It appears that there are several mechanisms involved in this interaction and that more than one could be involved with a particular metal. It is clear that selenium does not protect animals against heavy metal toxicity by increasing their excretion instead, it causes an increased retention of metals (Parizek et al, 1971 Wagner et al., 1975 Diplock, 1976 Ganther, 1978 Whanger, 1981). A summary of the proposed interactions of selenium with cadmium, mercury, and silver is presented in Fig. 1. 

Another possibility is that the selenide form of selenium may react with metals to form insoluble metal selenides (reaction 3), thus reducing their toxicity. Consistent with this possibility, Groh et al. (1973), using the scanning transmission electron microscope, found that the addition of mercury and selenium to diets for rats results in the formation of dense aggregates of black particles, composed of mercury and selenium, in the cells of the liver and kidneys. The molar ratio of selenium to mercury (Ganther and Sunde, 1974 Koeman et ai, 1975 Kosta et al., 1975) or cadmium (Gasiewicz and Smith, 1976) in the tissues is also consistent with this possibility. 

Since vitamin E prevents the promotion of liver necrosis in rats by silver, and since this element appears to promote in vivo peroxidation, one of the ways that silver brings about its damaging effects may be by generation of peroxides (reaction 5). It has been proposed that vitamin E functions in inhibiting the formation of peroxides, whereas selenium, as GSH-Px, is involved in the breakdown of peroxides (reaction 6) to the less harmful, alcohols (Hoekstra, 1975). If metals such as mercury or silver inhibit the activity of this enzyme (reaction 7), this could result in tissue damage due to peroxide accumulation, particularly when vitamin E is also absent or low. Evidence has been presented that selenide is an intermediate in GSH-Px synthesis (Sunde and Hoekstra, 1980). Thus, an adequate supply of selenide should generate more GSH-Px (reaction 8) and sele-noamino acids, such as selenocysteine (reaction 9). An adequate supply of selenide would allow the animal to more adequately combat the detrimental effects of heavy metals. Finally, the involvement of tissue sulfhy-dryls in the formation of bis(methylmercuric)selenide is another possible mechanism of heavy metal detoxification by selenium (Iwata et al., 1981  

Naganuma et al., 1980). Selenide has been found to react with methyl-mercury in vitro to form bis(methylmercuric)selenide (reaction 10), but either protein sulfhydryl groups or reduced glutathione was needed when other chemical forms of selenium were used (Iwata et al., 1981). The detection of selenide, although at very low levels, in the tissues of mice treated with selenium and methylmercury (Naganuma et al., 1980) is evidence that this reaction occurs in animals. Hence, there are several possible mechanisms of interaction of selenium with cadmium, mercury, and silver, and many physiological aspects of this interaction still to be elucidated. 

---