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Ferritin as a source of iron for oxidative damage
Abstract
The generation of deleterious activated oxygen species capable of damaging DNA, lipids, and proteins requires a catalyst such as iron. Once released, ferritin iron is capable of catalyzing these reactions. Thus, agents that promote iron release may lead to increased oxidative damage. The superoxide anion formed enzymatically, radiolytically, via metal-catalyzed oxidations, or by redox cycling xenobiotics reductively mobilizes ferritin iron and promotes oxidative damage. In addition, a growing list of compounds capable of undergoing single electron oxidation/reduction reactions exemplified by paraquat, adriamycin, and alloxan have been reported to release iron from ferritin. Because the rapid removal of iron from ferritin requires reduction of the iron core, it is not surprising that the reduction potential of a compound is a primary factor that determines whether a compound will mobilize ferritin iron. The reduction potential does not, however, predict the rate of iron release. Therefore, ferritin-dependent oxidative damage may be involved in the pathogenesis of diseases where increased superoxide formation occurs and the toxicity of chemicals that increase superoxide production or have an adequate reduction potential to mobilize ferritin iron.
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“One interpretation for these disappointing results, that is consistent with the general theme of this review, involves the recognition that a variety of antioxidants can in fact act as pro-oxidants and thus actually promote the production of OH• radicals in the presence of inappropriately or inadequately liganded Fe(II) [130,528,1602,1604,1659,1660].”
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 [1602]
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Metadata
- Authors
- Reif, D. W.
- Corresponding author
- Reif, David W.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 1992
- Volume
- 12
- Issue
- 5
- Pages
- 417-427
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W1972164300
- Cited by
- 357
- References
- 95
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 10 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 10 · 2014: 11 · 2013: 10 · 2012: 7
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- ferritin, iron release, oxidative damage, superoxide, iron-catalyzed oxidation, redox potential, one-electron oxidation, paraquat, doxorubicin, alloxan, radiolysis, metal-catalyzed oxidation, DNA damage, lipid peroxidation, protein oxidation
- MeSH terms
- Animals, Ferritins, Humans, Iron, Nitric Oxide, Oxidation-Reduction, Oxygen, Superoxides, Lipid Peroxidation, Xenobiotics
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