Stereospecific glutathione conjugation of (R)- and (S)-2-bromoisovalerylurea in freshly isolated rat kidney proximal tubular cells

Biochem Pharmacol. 1992 Feb 18;43(4):902-4. doi: 10.1016/0006-2952(92)90260-p.

Abstract

The glutathione conjugation of 2-bromoisovalerylurea (BIU) was studied in isolated proximal tubular kidney cells of the rat. Racemic (R,S)-BIU was incubated with the cell suspension, and the incubation medium was analysed for the diastereomeric glutathione (GSH) conjugates, cysteine conjugates and mercapturates that can be formed from (R)- and (S)-BIU. Only the mercapturate formed from (R)-BIU was found, as well as its cysteine precursor. No GSH conjugates were detected. These results indicate that these cells conjugate only the (R)-BIU enantiomer, and that the GSH conjugate is immediately further metabolized to its cysteine conjugate and mercapturate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / metabolism
  • Animals
  • Bromisovalum / metabolism*
  • Bromisovalum / pharmacology
  • Cells, Cultured / metabolism
  • Chromatography, High Pressure Liquid
  • Cysteine / metabolism
  • Glutathione / metabolism*
  • Kidney Tubules, Proximal / metabolism*
  • Male
  • Molecular Conformation
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism

Substances

  • Bromisovalum
  • Glutathione
  • Cysteine
  • Acetylcysteine