The formation and biotransformation of cysteine conjugates of halogenated ethylenes by rabbit renal tubules

C. D. Hassall, A Jay Gandolfi, R. C. Duhamel, K. Brendel

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21 Scopus citations

Abstract

The nephrotoxicity of chlorotrifluoroethylene (CTFE) was examined using isolated rabbit renal tubules suspensions. Exposure of the tubules to CTFE resulted in consumption of CTFE, formation of a glutathione conjugate and inhibition of active organic acid transport. Synthetic cysteine, N-acetylcysteine or glutathione conjugates of CTFE inhibited transport indicating S-conjugation as a possible toxic pathway. 1,2-dichlorovinyl glutathione (DCVG), a model synthetic glutathione conjugate, was used to examine the degradation and toxicity of these conjugates. DCVG inhibited rabbit renal tubule transport in vivo and in vitro. The DCVG was found to be degraded with the evolution of glutamine and glycine to produce the ultimate nephrotoxicant, dichlorovinyl cysteine. Dichlorovinyl cysteine is then bioactivated with the release of ammonia. This sequential degradation explains the latency of DCVG-induced renal transport inhibition relative to dichlorovinyl cysteine. It is now evident that certain halogenated ethylenes are capable of being biotransformed to glutathione conjugates in the kidney with their subsequent hydrolysis to nephrotoxic cysteine conjugates.

Original languageEnglish (US)
Pages (from-to)283-297
Number of pages15
JournalChemico-Biological Interactions
Volume49
Issue number3
DOIs
Publication statusPublished - 1984

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Keywords

  • Active organic acid base transport
  • Chlorotrifluoroethylene
  • Dichlorovinyl cysteine
  • Glutathione S-conjugation
  • Nephrotoxins
  • Renal tubule suspensions

ASJC Scopus subject areas

  • Toxicology

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