ABSTRACT
Previous work has suggested that endogenous sulfhydryls, such as glutathione (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(cysteinylglycine)2 [Hg(CYS-GLY)2] and Hg(CYS)2 were investigated in rabbit renal proximal tubule suspensions (RPT). The intracellular K+ was used as 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 was: Hg(CYS)2 > Hg(CYS-GLY)2 > Hg(SG)2. However, no significant difference among the mercury contents in the tubules exposed to these synthesized mercury-thiol-complexes was detected. Acivicin (0.25 mM), an inhibitor of gamma-glutamyltranspeptidase (GGT), decreased the toxicity of Hg(SG)2 in a manner that did not decrease the uptake of mercury in the tubules. This suggests 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(+)-dependent 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 transporter, did not have significant effect on their uptake and toxicity. L-phenylalanine, an inhibitor of the neutral amino acid decreased the uptake of mercury, but to a lesser extent. This suggested that neutral amino acid transporter seemed to play a role, in part, in the toxicity and uptake of synthesized Hg(CYS)2. In summary, the data suggested that basolateral transport is important for the toxicity of the three synthesized mercury-thiol-complexes, and a variety of mechanisms are involved in the toxicity and uptake of these complexes in isolated rabbit RPT.
Subject(s)
Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Organomercury Compounds/pharmacokinetics , Organomercury Compounds/toxicity , Sulfhydryl Compounds/pharmacokinetics , Sulfhydryl Compounds/toxicity , Animals , Biological Transport , Kidney Tubules, Proximal/enzymology , Male , Organomercury Compounds/chemical synthesis , Rabbits , Sulfhydryl Compounds/chemical synthesis , Time Factors , gamma-Glutamyltransferase/metabolismABSTRACT
We present three examples to illustrate the use of backscattering spectrometry to determine film stoichiometry, areal density, and impurity levels in optical coatings. Helium-ion beams with energies in the 1.5-5.0-MeV range were used to analyze (1) a magnesium fluoride coating, (2) a tungsten/silicon multilayer soft x-ray mirror, and (3) a trilayer optical data storage film.