Formation of Reactive Metabolites and Appearance of Antiorganelle Antibodies in Man

  • D. Mansuy
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


The toxic effects of many xenobiotics are very often not due to the parent compound itself but to reactive intermediates or metabolites formed in situ inside the cell. These reactive species may bind covalently to cell proteins leading to various cell disorders and eventually to toxic effects.


Human Liver Microsome Reactive Metabolite Thiophene Ring Tienilic Acid Human Liver Cytochrome 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beaune, P., Dansette, P.M., Mansuy, D., Kiffel, L., Finck, M., Amer, C., Leroux, J.P. and Homberg, J.C. (1987). Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc. of the National Academy of Sciences, USA, 84, 551–555.CrossRefGoogle Scholar
  2. Dansette, P.M., Amar, C., Smith, C.B., Neau, E., Pons, C. and Mansuy, D. (1989). In vitro, the 5-hydroxylation of tienilic acid is catalyzed by cytochrome P-450 in rat and human microsomes, in Cytochrome P-450, Biochemistry and Biophysics, Schuster I. Edit., Taylor and Francis, pp. 751–754.Google Scholar
  3. Dansette, P.M., Amar, C., Smith, C.B., Pons, C. and Mansuy, D. (1990). Oxidative activation of the thiophene ring by hepatic enzymes: hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes. Biochemical Pharmacology,in press.Google Scholar
  4. Homberg, J.C., Abuaf, N., Helmy-Khalil, S., Biour, M. et al. (1985). Drug-induced hepatitis with anti-intracytoplasmic organelle autoantibodies. Hepatology, 5, 722–727.CrossRefPubMedGoogle Scholar
  5. Mansuy, D., Dansette, P.M., Foures, C., Jaouen, M., Moinet, G. and Bayer, N. (1984). Metabolic hydroxylation of the thiophene ring: isolation of 5- hydroxytienilic acid as major urinary metabolite in man and rat. Biochemical Pharmacology, 33, 1429–1439.CrossRefPubMedGoogle Scholar
  6. Pohl, L.R., Satoh, H., Christ, D.D. and Kenna, J.G. (1988). The immunologicand metabolic basis of drug hypersensitivities. Annual Review of Pharmacology, 28, 367–387.Google Scholar
  7. Singer, T.P. (1985). Mitochondrial monoamine oxidase, in Biochemical Pharmacology and Toxicology, Zakim, D. and Vessey, D.A. Edit, Wiley J. and Sons, New-York, vol. 1, pp. 229–264.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • D. Mansuy
    • 1
  1. 1.Laboratoire de Chimie et Biochimie Pharmacologiques et ToxicologiquesUniversité René DescartesParis Cedex 06France

Personalised recommendations