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Cited by 668

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Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators

Open access
Kajarabille, Naroa, Latunde-Dada, Gladys O.·2019·International Journal of Molecular Sciences

Abstract

Iron, the fourth most abundant element in the Earth’s crust, is vital in living organisms because of its diverse ligand-binding and electron-transfer properties. This ability of iron in the redox cycle as a ferrous ion enables it to react with H2O2, in the Fenton reaction, to produce a hydroxyl radical (•OH)—one of the reactive oxygen species (ROS) that cause deleterious oxidative damage to DNA, proteins, and membrane lipids. Ferroptosis is a non-apoptotic regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is triggered when the endogenous antioxidant status of the cell is compromised, leading to lipid ROS accumulation that is toxic and damaging to the membrane structure. Consequently, oxidative stress and the antioxidant levels of the cells are important modulators of lipid peroxidation that induce this novel form of cell death. Remedies capable of averting iron-dependent lipid peroxidation, therefore, are lipophilic antioxidants, including vitamin E, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1) and possibly potent bioactive polyphenols. Moreover, most of the enzymes and proteins that cascade or interact in the pathway of ferroptosis such as a subunit of the cystine/glutamate transporter xc− (SLC7A11), glutathione peroxidase 4 (GPX4), and the glutamate–cysteine ligase (GCLC) iron metabolism genes transferrin receptor 1 (TfR1) ferroportin, (Fpn) heme oxygenase 1 (HO-1) and ferritin are regulated by the antioxidant response element of the transcription factor, Nrf2. These, as well as other radical trapping antioxidants (RTAs), are discussed in the current review.

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Metadata

Authors
Kajarabille, N., & Latunde-Dada, G. O.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-10-08
Volume
20
Issue
19
Pages
4968
ISSN
1422-0067 (ISSN-L)
OpenAlex
W2979398595
Cited by
668
References
76
FWCI
36.40
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators. https://app.cochat.ai/papers/10.3390/ijms20194968
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Kajarabille, N., & Latunde-Dada, G. O. (2019). Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms20194968

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