In vitro and in vivo nephrotoxicity of the L and D isomers of S-(1,2-dichlorovinyl)-cysteine

Toxicology. 1989 Sep;58(1):33-42. doi: 10.1016/0300-483x(89)90102-9.

Abstract

The toxicity of the optical isomers S-(1,2-dichlorovinyl)-L-cysteine (L-DCVC) and S-(1,2-dichlorovinyl)-D-cysteine (D-DCVC) was investigated in vivo and in vitro. In vitro studies, utilizing a rabbit renal cortical slice system, demonstrated toxicity due to both forms with the L-form being more toxic. Dose- and time-dependent decreases in intracellular K+ and LDH were observed. Both compounds produced an initial S3 lesion, L-DCVC at 10(-5) M (12 h), D-DCVC at 10(-4) M (8 h), followed by a lesion encompassing all proximal tubules. In vivo studies demonstrated elevated blood urea nitrogen values at 24 and 48 h with 25 mg/kg of either isomer. Histopathology indicated both D and L-DCVC produced a straight proximal tubular lesion by 48 h, the lesion produced by L-DCVC being more severe. The D and L isomers of DCVC were both shown to be toxic, the toxicity assessed in vitro corresponded well with the toxicity in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Culture Techniques
  • Cysteine / toxicity
  • Isomerism
  • Kidney Cortex / drug effects*
  • Kidney Cortex / metabolism
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / pathology
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Potassium / metabolism
  • Rabbits
  • Time Factors

Substances

  • S-(1,2-dichlorovinyl)cysteine
  • L-Lactate Dehydrogenase
  • Cysteine
  • Potassium