The Mechanism of Biliary Excretion of Methyl Mercury: Studies with Methylthiols

Abstract

The S-methylated derivatives of N-acetylphenicillamine, thiola and cysteine as well as methyl iodide, decreased biliary excretion of methyl mercury markedly. Excretion of sulfhydryl in bile was not influenced by S-methyl-cysteine, S-methylthiola, S-methyl-N-acetylpenicillamine or a low dose of methyliodide (0.5 mmol/kg body wt). Coupling of methyl mercury to glutathione in the rat liver before biliary excretion is apparently a glutathione S-transferase dependent reaction. The methylthiols tested, or metabolites of these compounds, are evidently likely to be inhibitors of S-transferase. The effect of S-methylcysteine and low doses of methyl iodide probably reflects glutathione S-transferase inhibition as both compounds are metabolized to the S-transferase inhibitor S-methylglutathione in the liver. A higher dose of methyl iodide (1 mmol/kg body wt) seems to deplete the liver of reduced glutathione through S-methylation as illustrated by decreased biliary excretion of sulfhydryl. S-methylthiola and S-methyl-N-acetylpenicillamine are metabolized in the liver to unknown components which are excreted in bile. Whether S-methylthiola and S-methyl-N-acetylpenicillamine are inhibitors of S-transferase themselves or cause inhibition through metabolites cannot be stated from this investigation.