The interrelationship between non-protein bound thiols and the biliary excretion of methylmercury

Abstract

The biliary excretion of methyl mercury was investigated in male rats injected with various thiol compounds, methionine and 3'-methyl-4-dimethyl-azobenzene (3'-MeDAB) after the i.v. administration of 1.0 mg kg of Hg as Me 20HgCl. All the thiol compounds (2 m-moles of glutathione (GSH) and 4 m-moles kg of cysteine, d-penicillamine or dimercaptosuccinic acid (DMSA) reduced the blood concentration of Me 203Hg +, but only cysteine, GSH and d-penicillamine increased the liver content of mercury and its biliary excretion. No significant changes were seen in the volume of bile flow after treatment. There was no correlation between the increase in non-protein thiol concentration in blood and either the liver content or the biliary excretion of Me 203Hg +. Although those thiol compounds that stimulated the biliary excretion of methylmercury also increased the liver concentration of non-protein thiol groups, there was no proportionality between either the extent or time course of these effects. An initial inhibition of excretion was caused by 4 m-moles kg of cysteine though the concentration of non-protein thiols in the liver was at that time the highest. After the administration of cysteine and GSH, excretion increased from 30 to 120 min while the concentration of non-protein thiols in the liver declined. 3'-Methyl-4-dimethylazobenzene (3'-MeDAB) and methionine caused a larger increase in liver non-protein thiol concentration than GSH but their effect on the biliary excretion of Me 203Hg + was smaller. On the assumption that d-penicillamine spares GSH from other metabolic processes, these results are consistent with the role of GSH in the biliary excretion of methylmercury. They do not support a direct relationship between free GSH and the biliary excretion of methylmercury.