Nephrotoxicity pp 595-600 | Cite as

Bioactivation Mechanism and Cytotoxicity of S(2-Chloro-1,1,2-Trifluoroethyl)-L-Cysteine

  • Lawrence H. Lash
  • Wolfgang Dekant
  • M. W. Anders


Glutathione conjugation of electrophilic xenobiotics is an important cellular detoxication mechanism. The nephrotoxicity and nephrocarcinogenicity of certain halogenated alkenes, however, may be attributed to glutathione S-conjugate formation followed by metabolism of the glutathione S-conjugates to the corresponding cysteine S-conjugates, which are metabolised by renal cysteine conjugate β-lyase (β-lyase) to ammonia, pyruvate and a thiol (Dekant et al., 1986a,b; Elfarra and Anders, 1984). The thiols thus formed are thought to lose hydrogen halide or tautomerise to yield reactive, electrophilic species (Anders et al., 1987; Dekant et al., 1986c) that may be the ultimate toxic metabolites. The chemical nature of these metabolites formed from cysteine S-conjugates has, however, not been characterized.


Sulphide Glutathione Bromide Fluoride Cysteine 
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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Lawrence H. Lash
    • 1
  • Wolfgang Dekant
    • 2
  • M. W. Anders
    • 1
  1. 1.Department of PharmacologyUniversity of RochesterRochesterUSA
  2. 2.Institut fur ToxickologieUniversitat WurzburgWurzburgFederal Republic of Germany

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