INHIBITORY EFFECT OF SELENIUM ON BILIARY-SECRETION OF METHYL MERCURY IN RATS

The inhibitory effect of sodium selenite on biliary secretion of methy l mercury was examined in rats. The biliary secretion of methyl mercur y in rat treated with 1 mu mol/kg of methyl mercury was significantly decreased by administration of selenite at doses of 0.05 mu mol/kg or higher. In rats given 10 mu mol/kg of methyl mercury, marked depressio n of biliary secretion of mercury was observed when selenite was injec ted at a dose of 0.2 mu mol/kg. On the other hand, secretion of substa ntial amounts of selenium was observed when biliary secretion of mercu ry was depressed, When the concentration of selenium in the bile was h igher than 5 nmol/ml, biliary secretion of mercury was markedly depres sed independently of the dose of methyl mercury administered (1 mu mol /kg or 10 mu mol/kg). These results suggest that the degree of inhibit ory effect of selenite may be determined by the selenium concentration in the liver or the bile after treatment with selenite rather than th e molar ratio of the dose of methyl mercury and selenite. We concluded that the decrease in biliary secretion of methyl mercury induced by s elenite may result from inhibition of pathway for secretion of methyl mercury from liver to bile rather than the direct formation of a compe x between methyl mercury and selenium. Methyl mercury has been conside red to be secreted from liver to bile as a complex with glutathione (G SH). However, administration of selenite did not affect biliary secret ion of GSH or hepatic glutathione S-transferase activity, Moreover, ge l filtration of liver cytosol demonstrated that the distribution patte rn of hepatic methyl mercury between macromolecules and GSH was not si gnificantly changed by administration of selenite. These results sugge st that selenite does not; affect complex formation of methyl mercury with GSH at least in the liver. Selenite might specifically inhibit th e activity of the canalicular transporter(s) which transport complexes of methyl mercury and GSH from the liver to bile. (C) 1997 Academic P ress.