The Haber–Weiss reaction and mechanisms of toxicity

Kehrer, James P

doi:10.1016/s0300-483x(00)00231-6

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

The Haber–Weiss reaction and mechanisms of toxicity

Kehrer, James P·2000·Toxicology

DOI 10.1016/s0300-483x(00)00231-6

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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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Superoxide can react with ferric iron in the Haber-Weiss reaction to produce Fe(II), effecting redox cycling.
“Superoxide can also react with ferric iron in the Haber-Weiss reaction [67] to produce Fe(II) again, thereby effecting redox cycling:”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [67]
Superoxide can react with ferric iron in the Haber-Weiss reaction to produce Fe(II) again, thereby effecting redox cycling of the iron.
“Superoxide (also produced by mitochondria) can react with ferric iron in the Haber-Weiss reaction (Kehrer 2000) to produce Fe(II) again, thereby effecting redox cycling of the iron (Fig. 1):2”
From Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples (2010) · cites this paper as Kehrer 2000

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“Superoxide can also react with ferric Fe in the Haber – Weiss reaction (214 – 216) to produce Fe(II) again, thereby effecting redox cycling, and meaning the ‘ iron ’ is catalytic (Fig.”
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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 › 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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