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Selective activation of chemicals by the kidney: its relevance to toxicity and mutagenicity

  • E. A. Lock
  • T. Green

Abstract

A number of chemicals have been shown to undergo metabolism in the kidney, to metabolites which can covalently bind to macromolecules and produce toxicity. Both paracetamol (McMurtry et al., 1978; Mudge et al., 1978) and chloroform (Ilett et al., 1973; Kluwe et al., 1978) undergo metabolism in the kidney via cytochrome P-450 enzymes to ‘reactive’ metabolites which are thought to be responsible for the cellular necrosis. However, in both these cases, the cytochrome P-450 enzymes are also present in the liver, where these compounds also produce extensive centrilobular necrosis (Mitchell et al., 1973; Ilett et al., 1973). These compounds are therefore not entirely organ selective, and the extent of toxicity to the liver or kidney can be modified by altering the level of activation and deactivation enzymes in these target organs (Mitchell et al., 1973; Ilett et al., 1973; McMurtry et al., 1978; Kluwe et al., 1978).

Keywords

Renal Tumour Plasma Urea Centrilobular Necrosis Cysteine Conjugate Renal Tubular Necrosis 
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

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • E. A. Lock
    • 1
  • T. Green
  1. 1.Biochemical Toxicology SectionCentral Toxicology Laboratory, Imperial Chemical Industries PLCMacclesfieldUK

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