ISSN:
1432-1335
Keywords:
Key words Glutathione S-conjugate
;
Cysteine S-conjugate
;
Nephrotoxicity
;
Cysteine conjugate β-lyase
;
Organ specific toxicity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Several halogenated alkenes are nephrotoxic in rodents. A mechanism for the organ-specific toxicity to the kidney for these compounds has been elucidated. The mechanism involves hepatic glutathione conjugation to dihaloalkenyl or 1,1-difluoroalkyl glutathione S-conjugates, which are cleaved by γ-glutamyltransferase and dipeptidases to cysteine S-conjugates. Haloalkene-derived cysteine S-conjugates are substrates for renal cysteine conjugate β-lyases, which cleave them to form reactive intermediates identified as thioketenes (from chloroalkene-derived S-conjugates) or thionoacyl halides (from 1,1-difluoroalkyl S-conjugates). Alternatively, cysteine S-conjugates may be N-acetylated to excretable mercapturic acids. The formation of reactive intermediates by cysteine-conjugate β-lyase may play a role in the target-organ toxicity and in the possible renal tumorigenicity of several chlorinated olefins widely used in many chemical processes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004320050260
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