Cited by 1,418Redox biology and oxidative stressAntioxidant Activity and Oxidative StressFree Radicals and Antioxidants

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The Haber–Weiss reaction and mechanisms of toxicity

Kehrer, James P·2000·Toxicology

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Abstract

The concept that the highly reactive hydroxyl radical (HO) could be generated from an interaction between superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) was proposed (with Joseph Weiss) in Professor Haber's final paper published in 1934. Until it was recognized that free radicals are produced in biological systems, this finding seemed to have no relevance to biology. However, following the discovery that O(2)(-) was a normal cellular metabolite, it was quickly recognized that the Haber-Weiss reaction (O(2)(-)+H(2)O(2) -->HO+O(2)+HO(-)) might provide a means to generate more toxic radicals. Although the basic reaction has a second order rate constant of zero in aqueous solution and thus cannot occur in biological systems, the ability of iron salts to serve as catalysts was discussed by these authors. Because transition metal ions, particularly iron, are present at low levels in biological systems, this pathway (commonly referred to as the iron-catalyzed Haber-Weiss reaction) has been widely postulated to account for the in vivo generation of the highly reactive HO. Recent data documenting the importance of redox regulation of various cellular signaling pathways makes it clear that free radicals are essential for normal cellular function. However, this also makes it obvious that disruptions of free radical production or defenses at many different levels can lead to adverse effects on cells. While the generation of HO, which is by far the most reactive oxygen species, is generally indicative of an overtly toxic event, it is through studies at this level that we have reached a better understanding of free radicals as both signaling molecules and toxic species.

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“Ferrous iron can catalyze the formation of hydroxyl radicals through the Fenton reaction, which initiates LPO [78].”
Superoxide Activates Ferroptosis via the Haber‐Weiss Reaction and Enhances Age‐Related Macular Degeneration
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“Since the criticism was irrelevant to the biological system, the reaction was further supported by widely postulating that superoxide is a normal cellular metabolite and may produce hydroxyl radicals in vivo, although the basic reaction is slow in aqueous solution (Kehrer 2000).”
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“However, since this was not reflected in NF-κB activation, ROS were most probably generated through the iron-catalyzed Fenton reaction in case of MHG NPs, [51,52] or generated through photocatalytic surface reactivity of TiO2 P25 NPs [53].”
Background
Clues and new evidences in arterial hypertension: unmasking the role of the chloride anion
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“The formation of hydroxyl radicals (•OH) from H2O2 is catalysed by iron ions, called the Fenton or Haber–Weiss reaction [64].”
Background
The Potential Modulatory Effects of Exercise on Skeletal Muscle Redox Status in Chronic Kidney Disease
Mendes, S., Leal, D. V., Baker, L. A., Ferreira, A., Smith, A. C., & Viana, J. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076017 · Cited by 12
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“[45] Equally important is the noted increased generation of H2O2 in the EcV incubated cells, which interacts with SOA leading to the formation of the more reactive hydroxyl radicals [46] that react with purines and pyrimidines causing DNA damage [44] and subsequent lowered gene expression of the antioxidant enzymes.”
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Study on a 65‐mer peptide mimetic enzyme with GPx and SOD dual function
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Sulforaphane and Albumin Attenuate Experimental Intestinal Ischemia-Reperfusion Injury
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Hepatotoxicity Due to Mitochondrial Injury
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Ascorbate ameliorates Echis coloratus venom-induced oxidative stress in human fibroblasts
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“The demonstrated increased H 2 O 2 generation could have also interacted with SOA thus producing the more reactive hydroxyl radicals (48) known to react with purines and pyrimidines causing DNA damage and lowered antioxidant gene expression.”
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“Cu can induce HO · formation via the Haber–Weiss/Fenton reaction in the presence of H 2 O 2 [56].”
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“Free iron can generate highly reactive ROS directly through the Fenton and Haber–Weiss reactions (Kehrer, 2000).”
Background
Discovery of a Redox-Activatable Chemical Probe for Detection of Cyclooxygenase-2 in Cells and Animals
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“For example, in the absence of adequate levels of copper, H 2 O 2 can be converted to OH, which is a highly reactive oxidant.(31,56) Animal and human studies have indicated that the concentration of antioxidant scavengers is reduced in the presence of risk factors for CVD, as well as in the presence of overt atheroscl…”
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Lower Iron Levels Predict Acute Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage
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Maternal hemoglobin concentrations across pregnancy and child health and development from birth through 6–7 years
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An evaluation of pyrite as a component of respirable coal dust.
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“This radical together with other reactive oxygen species (ROS – singlet oxygen, hydrogen peroxide) can damage DNA, lipids and proteins that are important molecules mainly as enzymes, transporters, or antioxidants (Kehrer 2000).”
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“The oxidative dissolution of pyrite releases ferrous iron into the solution, which then interacts with dissolved molecular oxygen leading to the Haber–Weiss reaction mechanism (Kehrer 2000) and eventually the formation of H 2 O 2 (Rxns. ).”
Polyoxometalates in environmental remediation and energy storage
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Authors: Kehrer, J. P.
Affiliations: The University of Texas at Austin (US)
Corresponding author: Kehrer, James P
Venue: Toxicology
Publisher: Elsevier BV
Published: 2000-08
Volume: 149
Issue: 1
Pages: 43-50
ISSN: 0300-483X (ISSN-L)
DOI: 10.1016/s0300-483x(00)00231-6
OpenAlex: W2126473492
Cited by: 1,418
References: 39
Citations by year: 2026: 46 · 2025: 71 · 2024: 90 · 2023: 91 · 2022: 101 · 2021: 101 · 2020: 91 · 2019: 65 · 2018: 76 · 2017: 72 · 2016: 71 · 2015: 62 · 2014: 48 · 2013: 65 · 2012: 59
FWCI: 1.20
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Toxicology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01es009791-04, 5r01hl051005-05, 5r01hl048035-07)
National Heart, Lung, and Blood Institute (HL 48035, HL 51005)
National Institute of Environmental Health Sciences (ES09791)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
Keywords: Haber-Weiss reaction, hydroxyl radicals, superoxide, hydrogen peroxide, free radicals, reactive oxygen species, oxidative stress, redox signaling, toxicity mechanisms, transition metal catalysis
MeSH terms: Animals, Humans, Hydrogen Peroxide, Superoxides, Hydroxyl Radical, Oxidative Stress

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The Haber–Weiss reaction and mechanisms of toxicity

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