Toxicity and transport of three synthesized mercury-thiol-complexes in isolated rabbit renal proximal tubule suspensions

Previous work has suggested that endogenous sulfhydryls, such as glutathion e (GSH) and cysteine, are involved in the uptake and toxicity of HgCl2. To study this possibility uptake and toxicity of synthesized Hg(SG)(2), Hg(cys teinylglycine)(2) [Hg(CYS-GLY)(2)] and Hg(CYS)(2) were investigated in rabb it renal proximal tubule suspensions (RPT). The intracellular K+ was used a s a toxicity indicator, and the mercury content in the tubules was measured by proton induced x-ray emission analysis. The toxicity rank order of the three synthesized mercury-thiol-complexes from the highest to the lowest wa s: Hg(CYS)(2) > Hg(CYS-GLY)(2) > Hg(SC)(2). However, no significant differe nce among the mercury contents in the tubules exposed to these synthesized mercury-thiol-complexes was detected. Acivicin (0.25mM), an inhibitor of ga mma-glutamyltranspeptidase (GGT), decreased the toxicity of Hg(SG)(2) in a manner that did not decrease the uptake of mercury in the tubules. This sug gests that the toxicity of Hg(SG)(2) requires processing to Hg(CYS-GLY)(2) or Hg(CYS)(2), while Hg(SG)(2) may be taken up by the tubules via Na+-depen dent GSH transporter since 10 mM acivicin, an inhibitor of this transporter dramatically decreased the uptake of Hg(SG)(2). Organic anion transporter plays a minor role, if any, in the toxicity and uptake of Hg(SG)(2) and Hg( CYS)(2) since p-aminohippuric acid (PAH), an inhibitor of organic anion tra nsporter, did not have significant effect on their uptake and toxicity. L-p henylalanine, an inhibitor of the neutral amino acid decreased the uptake o f mercury, but to a lesser extent. This suggested that neutral amino acid t ransporter seemed to play a role, in part, in the toxicity and uptake of sy nthesized Hg(CYS)(2). In summary, the data suggested that basolateral trans port is important for the toxicity of the three synthesized mercury-thiol-c omplexes, and a variety of mechanisms are involved in the toxicity and upta ke of these complexes in isolated rabbit RPT.