Correlation of the in vivo and in vitro renal toxicity of s-(1,2-dichlorovinyl)-l-cysteine

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

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The major site at which vinyl cysteine conjugates exert nephrotoxicity is the proximal tubule. Since this is the site of all active anion and cation transport, tubule transport integrity was used to assess nephrotoxicity. Tubules were isolated from young rabbits to study the in vivo and in vitro nephrotoxicity of the conjugate, dichlorovinyl cysteine (DCVC). In vivo exposure to DCVC caused necrosis in the pars recta region of the proximal tubules (20-100 mg/kg ip) and a dose-dependent decrease in tubular active transport. Addition of DCVC to the perfused kidney and tubule suspensions resulted in similar decreases in tubular organic ion transport. At 0.01 mM DCVC, transport was similar to controls while 1 mM DCVC completely inhibited active accumulation of the organic ions. Thus kidney tubule active transport is similarly inhibited in vivo and in vitro by DCVC indicating that bioactivation of DCVC and inhibition of active transport occur directly in the renal tubule.

Original languageEnglish (US)
Pages (from-to)507-520
Number of pages14
JournalDrug and Chemical Toxicology
Volume6
Issue number6
DOIs
Publication statusPublished - 1983

    Fingerprint

ASJC Scopus subject areas

  • Chemical Health and Safety
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Chemistry(all)

Cite this