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November 20, 2001Biochemistry

Peroxidase- and Nitrite-Dependent Metabolism of the Anthracycline Anticancer Agents Daunorubicin and Doxorubicin

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Key result

Oxidation of doxorubicin and daunorubicin by lactoperoxidase and hydrogen peroxide is highly dependent on nitrite concentration and pH, leading to rapid and irreversible degradation.

Population

In vitro biochemical models of doxorubicin (DXR) and daunorubicin (DNR)

Comparison

Lactoperoxidase/H2O2 and horseradish… vs Peroxidase/H2O2 systems in the absence of nitrite

Design

Preclinical

Authors

KRKrzysztof J. ReszkaNational Institute of Environmental Health SciencesMMMichael L. McCormickHamilton CollegeBBBradley E. BritiganNebraska Medical Center

Discussion

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Implication

Anthracycline chromophore loss via LPO/H2O2/NO2- may occur in inflammatory settings; leaves open relevance to cardiotoxicity or dosing.

Structured PICO

P
Population
In vitro biochemical models of doxorubicin (DXR) and daunorubicin (DNR)
I
Intervention
Lactoperoxidase (LPO)/H2O2 and horseradish peroxidase (HRP)/H2O2 systems in the presence of nitrite (NO2-)
C
Comparator
Peroxidase/H2O2 systems in the absence of nitrite
O
Outcome
Oxidative degradation of anthracycline chromophores and generation of semiquinone radicals measured by spectrophotometric and EPR techniquessurrogate

This study identifies a novel peroxidase- and nitrite-dependent mechanism for the oxidative transformation of anthracyclines, which may contribute to their in vivo biological activity and toxicity.

Cite This Study

Reszka et al. (2001) studied this question. Lactoperoxidase/H2O2/nitrite system vs. Absence of nitrite or HRP/H2O2/nitrite was evaluated on Oxidative degradation of anthracycline chromophores. Oxidation of doxorubicin and daunorubicin by lactoperoxidase and hydrogen peroxide is highly dependent on nitrite concentration and pH, leading to rapid and irreversible degradation.

synapsesocial.com/papers/6a6c8bf226a7f98052db42cbhttps://doi.org/10.1021/bi011869c
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Doxorubicin cardiotoxicity: analysis of prevailing hypotheses1990 · 692 citations
  2. 2Augmentation of Cancer Chemotherapy by Preinjection of Human Macrophage Colony‐stimulating Factor in L1210 Leukemic Cell‐inoculated Mice1995 · 12 citations
  3. 3Adriamycin analogs. Periodate oxidation of adriamycin1976 · 22 citations
  4. 4Hammett pσ correlation for reactions of lactoperoxidase compound II with phenols1993 · 29 citations
  5. 5The Lactoperoxidase System Functions in Bacterial Clearance of Airways2000 · 177 citations