Identification of the 1-cyano-3,4-epithiobutane-derived urinary mercapturic acid n-acetyl-s-(4-cyano-2-thio-1-butyl)-cysteine in male fischer 344 rats
✍ Scribed by Jan L. Vansteenhouse; Judith S. Prescott; Steven A. Barker
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 167 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0260-437X
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✦ Synopsis
1-Cyano-3,4-epithiobutane (CEB), a naturally occurring nitrile derived from cruciferous plants, causes nephrotoxicity in male Fischer 344 rats. Nephrotoxicity induced by CEB is dependent on glutathione (GSH) conjugation and bioactivation. Conjugation with GSH and subsequent metabolism leads to the formation of specific urinary metabolites. The objectives of the present study were to identify CEB-derived urinary metabolites and quantify urinary non-protein thiols and thioethers in male Fischer 344 rats. Animals received 125 mg kg(-1) of CEB alone or following pretreatment with one of three selective inhibitors of GSH metabolism: acivicin, probenecid or aminooxyacetic acid. Total non-protein urinary thiol and urinary thioether concentrations were elevated in all treated groups at 12 and 24 h; however, elevations in non-protein thiols were not significantly greater in rats administered CEB alone as compared to negative controls. A single predominant urinary metabolite was identified as the CEB-derived mercapturic acid N-acetyl-S-(4-cyano-thio-1-butyl)-cysteine. Evidence for other CEB-derived metabolites was also demonstrated. These findings represent the identification of a unique compound and provide further evidence for the importance of GSH conjugation as a significant pathway in CEB metabolism.