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

Hongbing Wei, Li Qiu, Kevin K. Divine, M. D. Ashbaugh, L. C. McIntyre, Quintus Fernando, A Jay Gandolfi

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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 (0.25mM), an inhibitor of γ-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.

Original languageEnglish (US)
Pages (from-to)323-341
Number of pages19
JournalDrug and Chemical Toxicology
Volume22
Issue number2
StatePublished - 1999

Fingerprint

Proximal Kidney Tubule
Mercury
Sulfhydryl Compounds
Toxicity
Suspensions
cysteinylglycine
Rabbits
acivicin
Organic Anion Transporters
Neutral Amino Acid Transport Systems
p-Aminohippuric Acid
Neutral Amino Acids
Mercuric Chloride
Amino acids
Negative ions
Phenylalanine
Glutathione
Cysteine
Protons
X-Rays

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Toxicity and transport of three synthesized mercury-thiol-complexes in isolated rabbit renal proximal tubule suspensions. / Wei, Hongbing; Qiu, Li; Divine, Kevin K.; Ashbaugh, M. D.; McIntyre, L. C.; Fernando, Quintus; Gandolfi, A Jay.

In: Drug and Chemical Toxicology, Vol. 22, No. 2, 1999, p. 323-341.

Research output: Contribution to journalArticle

Wei, Hongbing ; Qiu, Li ; Divine, Kevin K. ; Ashbaugh, M. D. ; McIntyre, L. C. ; Fernando, Quintus ; Gandolfi, A Jay. / Toxicity and transport of three synthesized mercury-thiol-complexes in isolated rabbit renal proximal tubule suspensions. In: Drug and Chemical Toxicology. 1999 ; Vol. 22, No. 2. pp. 323-341.
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AU - Fernando, Quintus

AU - Gandolfi, A Jay

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