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Science 3 September 1976:
Vol. 193. no. 4256, pp. 901 - 903
DOI: 10.1126/science.7838
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Articles

Science, Vol 193, Issue 4256, 901-903
Copyright © 1976 by American Association for the Advancement of Science

articles

Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat

SD Nelson, Mitchell JR, JA Timbrell, WR Snodgrass, and GB Corcoran 3rd

Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Uniform Procedure of 1H NMR Analysis of Rat Urine and Toxicometabonomics Part II: Comparison of NMR Profiles for Classification of Hepatotoxicity.
W. G. E. J. Schoonen, C. P. A. M. Kloks, J.-P. H. T. M. Ploemen, M. J. Smit, P. Zandberg, G. J. Horbach, J.-R. Mellema, C. Thijssen-vanZuylen, A. C. Tas, J. H. J. van Nesselrooij, et al. (2007)
Toxicol. Sci. 98, 286-297
   Abstract »    Full Text »    PDF »
N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark.
G. Lower Jr, T Nilsson, C. Nelson, H Wolf, T. Gamsky, and G. Bryan (2007)
Int. J. Epidemiol.
   Full Text »    PDF »
Hydrazine, Cancer, the Internet, Isoniazid, and the Liver.
M. Black and H. Hussain (2000)
Ann Intern Med 133, 911-913
   Full Text »    PDF »
Isoniazid - and rifampicin-induced oxidative hepatic injury - protection by N-acetylcysteine.
S Attri, S V Rana, K Vaiphei, C P Sodhi, R Katyal, R C Goel, C K Nain, and K Singh (2000)
Human and Experimental Toxicology 19, 517-522
   Abstract »    PDF »
In Vivo Characterization of T-794, a Novel Reversible Inhibitor of Monoamine Oxidase-A, as an Antidepressant with a Wide Safety Margin.
M. Kato, T. Katayama, H. Iwata, M. Yamamura, Y. Matsuoka, and H. Narita (1998)
J. Pharmacol. Exp. Ther. 284, 983-990
   Abstract »    Full Text »    PDF »
Promutagenic Alkyl Lesions are Induced in the Tissue DNA of Animals Treated with Isoniazid.
R. Saffhill, S. Fida, M. Bromley, and P.J. O'Connor (1988)
Human and Experimental Toxicology 7, 311-317
   Abstract »    PDF »
Urinary Metabolic Profile of Isoniazid in Patients who Develop Isoniazid-related Liver Damage.
J.A. Timbrell and J.M. Wright (1984)
Human and Experimental Toxicology 3, 485-495
   Abstract »    PDF »


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