Evidence for the active renal secretion of S-pentachlorophenyl-N-acetyl-L-cysteine by female rats

Biochem Pharmacol. 1983 Dec 15;32(24):3797-801. doi: 10.1016/0006-2952(83)90152-1.

Abstract

Male and female rats received 50 mumoles of pentachloronitrobenzene/kg by oral intubation daily for seven days. The final excreta were hydrolysed and analysed by electron capture GLC for the presence of pentachlorobenzenethiol and tetrachloro-1,4-benzenedithiol (derived from the equivalent N-acetylcysteine conjugates). No differences were found between the sexes for faeces and bile but the urinary excretion of both thiols by females was more than 10-fold greater than males. A similar result for urine was obtained following i.p. administration of a single 20 mumoles/kg dose of S-pentachlorophenyl-N-acetyl-L-cysteine (pentachlorophenyl mercapturate); in addition co-treatment with probenecid did not greatly change excretion by the males but considerably reduced excretion by females. The sex difference in the urinary levels of pentachlorophenyl N-acetylcysteine after 40 and 100 mumoles/kg doses of pentachloronitrobenzene was confirmed by h.p.l.c. of the mercapturate and again probenecid inhibited the excretion. Analysis of urine by TLC following a dose of [14C]hexachlorobenzene (8 muCi/kg; 0.67 mumoles/kg) showed that more radioactivity was associated with the mercapturate from female rats than males. The results suggest that S-pentachlorophenyl-N-acetyl-L-cysteine, a metabolite of hexachlorobenzene and pentachloronitrobenzene, may be excreted by an active renal secretion which is particularly developed in female F344 rats.

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / urine
  • Animals
  • Bile / metabolism
  • Feces / analysis
  • Female
  • Isoxazoles / pharmacology
  • Kidney / metabolism*
  • Male
  • Nitrobenzenes / metabolism
  • Probenecid / pharmacology
  • Rats
  • Rats, Inbred F344
  • Sex Factors

Substances

  • Isoxazoles
  • Nitrobenzenes
  • pentachlorophenylmercapturic acid
  • acivicin
  • Probenecid
  • quintozene
  • Acetylcysteine