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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“These data are consistent with observations that, in most organisms, intracellular iron levels are tightly regulated to avoid forming toxic hydroxyl radicals and superoxide anions via HaberWeiss-Fenton catalysis (9).”
Background
Serum hepcidin concentrations correlate with serum iron level and outcome in patients with intracerebral hemorrhage
Xiong, X., Chen, J., Zhu, W., Zhao, T., Zhong, Q., Zhou, K., Meng, Z., Wang, Y., Wang, P., Huang, F., et al. (2015) · Neurological Sciences · doi:10.1007/s10072-015-2266-2 · Cited by 23
“Iron that is deposited in the perihematoma after ICH, derived from the erythrocyte degradation product heme, can produce a large number of toxic free radicals through the Haber–Weiss reaction [3] and also cause DNA damage [4, 5].”
Background
Comparative Analysis of ROS Network Genes in Extremophile Eukaryotes
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“Another major source of downstream ROS occurs through the reaction of metal ions with hydrogen peroxide (H2O2) to produce the unstable hydroxyl radical, particularly via Haber–Weiss and Fenton-type reactions [12].”
Background
Plasma activated media and direct exposition can selectively ablate retinoblastoma cells
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“OH damages DNA, proteins and membranes (10).”
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“Iron chelation ability Iron-chelation may render important antioxidative effects by retarding metal-catalyzed oxidation (Kehrer, 2000).”
Background
Synthesis of nickel(II) complexes of isatin thiosemicarbazone derivatives: in vitro anti-cancer, DNA binding, and cleavage activities
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“the reaction of H2O2 and O2•– catalyzed by iron [62].”
Background
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“Reactivated oxygen species (ROS) such as superoxide radicals, hydrogen peroxide, and hydroxyl radicals are generated in organism from the incomplete reaction of oxygen during aerobic metabolism or from exposure to environmental agents (Kehrer 2000; Kim et al. 2001; Reuter et al. 2010).”
Background
Effects of β-alanine administration on selected parameters of oxidative stress and phosphoryltransfer network in cerebral cortex and cerebellum of rats
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Background
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“Hydroxyl free radicals are mainly formed from H2O2 by the iron-catalyzed Fenton reaction or by the Haber–Weiss reaction [50].”
Background
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“1 Damages caused by ROS and RNS in vivo ROS and RNS, when not detoxified, lead to intracellular damage, by being key components in the oxidation of membrane lipids, amino acids, DNA or thiol-containing molecules [20,23].”
Background
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Background
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BackgroundMethod
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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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