Effects of Methylmercury and Organic Acid Mercurials on the Disposition of Exogenous Selenium in Rats

Abstract

Interaction of methylmercury (MM), an environmental and industrial toxicant, with selenium is well known but incompletely understood. Therefore, the effects of MM (10 μmol/kg iv) on the disposition of exogenous selenium were compared with those of other organic mercurials (merbromine, mercuribenzene sulfonic acid, and mercuribenzoic acid) in anesthetized bile duct-cannulated rats injected with sodium [75Se]selenite (10 μmol/kg iv). The mercurial organic acids (10 μmol/kg iv) differed strikingly from MM in their influence on selenium disposition. They promoted renal and hepatic accumulation as well as biliary excretion of selenium but decreased distribution to the muscle, testis, and brain as well as the pulmonary excretion of selenium. In contrast, MM altered selenium distribution in an opposite fashion: it diminished the biliary output of selenium and enhanced selenium exhalation. GC–MS analysis verified that this latter paradoxical effect resulted from increased exhalation of dimethyl selenide. Further studies indicated that the MM-induced increase in pulmonary excretion of dimethyl selenide cannot be due to a diminished conversion of this volatile selenium compound to trimethylselenonium ion (TMSe+), because MM influenced neither the urinary excretion nor the hepatic and renal concentration of TMSe+ in selenite-injected rats. Compared to the selenite-exposed rats, the selenite plus MM-injected animals exhibited a significant rise in the hepatic level of S-adenosylmethionine (SAME), the endogenous methyl donor in selenium methylation, and the ratio of SAME to S-adenosylhomocysteine. Based on these and others' observations, it is hypothesized that MM may increase hepatic availability of SAME in selenite-dosed rats by counteracting selenite-induced inactivation of SAME synthetase, thereby facilitating SAME synthesis, and/or by acting as a methyl donor in formation of dimethyl selenide, thereby sparing SAME. In summary, the toxicologically and ecologically relevant interaction of MM and selenite is not mimicked by organic acid mercurials, possibly because it results in formation of lipophilic Hg- and Se-containing common compound(s) and because it also appears to involve methyl transfer from MM to selenium.