Evidence for the active renal secretion of S-pentachlorophenyl-N-acetyl-L-cysteine by female rats.
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.
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism; D005243:Feces / Q000032:analysis; D005260:Female; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D007555:Isoxazoles; D009578:Nitrobenzenes; C027672:pentachlorophenylmercapturic acid; C006303:acivicin; D011339:Probenecid; C005805:quintozene; D000111:Acetylcysteine