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Related Experiment Videos

Rat liver nuclear nifurtimox nitroreductase activity

E G de Toranzo1, D M Herrera, J A Castro

  • 1Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, Pcia. de Buenos Aires, Argentina.

Research Communications in Molecular Pathology and Pharmacology
|March 5, 1998
PubMed
Summary

Nifurtimox (Nfx), used for Chagas' disease, shows toxicity linked to its metabolism. Rat liver nuclei possess Nfx-nitroreductase activity, suggesting reactive metabolites may cause long-term harm.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Toxicology

Background:

  • Nifurtimox (Nfx) treats American Trypanosomiasis (Chagas' disease).
  • Nfx exhibits mutagenic, reproductive, and carcinogenic toxic effects.
  • Toxicity is associated with NADPH-dependent nitroreductive metabolism and reactive oxygen species.

Purpose of the Study:

  • Investigate Nifurtimox-nitroreductase activity in rat liver nuclei.
  • Determine the metabolic pathways of Nifurtimox.
  • Explore the relationship between Nifurtimox metabolism and its toxic effects.

Main Methods:

  • Assay of Nifurtimox-nitroreductase (Nfx-ase) activity in rat liver nuclei.
  • Evaluation of Nfx-ase activity under varying oxygen and carbon monoxide conditions.

Related Experiment Videos

  • Assessment of Nifurtimox's effect on lipid peroxidation.

    • Main Results:

    • Rat liver nuclei exhibit Nifurtimox-nitroreductase activity.
    • This activity is abolished under oxygen and partially inhibited by carbon monoxide.
    • Nifurtimox does not induce lipid peroxidation.
    • Nifurtimox is metabolized by both cytochrome P450 and NADPH P450 reductase, predominantly the latter.

    Conclusions:

    • Nifurtimox undergoes significant nitroreduction in rat liver nuclei.
    • The formation of reactive metabolites near DNA and nuclear proteins may explain Nifurtimox's long-term toxicity.
    • NADPH P450 reductase plays a major role in Nifurtimox biotransformation.