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

Abstract

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.

Keywords

Hydrogen Sulphide Benzyl Bromide Hydrogen Fluoride Bovine Kidney Acylating Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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