Extracellular Iron(II) Can Protect Cells from Hydrogen Peroxide

Hempel, S. L.; Buettner, Garry R.; Wessels, D. A.; Galvan, George M.; O’Malley, Yunxia

doi:10.1006/abbi.1996.0268

Cited by 25 publications

(16 citation statements)

References 9 publications

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“…Paradoxically, extracellular iron can in some circumstances protect cells from H 2 O 2 -induced toxicity [20, 21, 26, 27] by initiating the Fenton reaction outside the cell; thus H 2 O 2 is removed and the highly oxidizing hydroxyl radical reacts with media components, leading to minimal damage to cells. In order to investigate the role of intracellular labile iron, we used the iron chelator 8-hydroxyquinoline (HQ).…”

Section: Resultsmentioning

confidence: 99%

“…HO • is very reactive and as such has an extremely limited diffusion distance, only about 6 nm in cells [19]. In cell culture experiments, introduction of Fe 2+ to media containing H 2 O 2 can actually protect cells [20, 21] because the H 2 O 2 in the media is removed; HO • generated by the Fenton reaction in the media will have little consequence, as the majority will react with media components and not cells. Removal of extracellular H 2 O 2 will minimize any possible site-specific oxidative damage to intracellular macromolecules, such as DNA.…”

Section: Introductionmentioning

confidence: 99%

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Role of labile iron in the toxicity of pharmacological ascorbate

Wagner

Buettner

et al. 2015

Free Radical Biology and Medicine

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Pharmacological ascorbate has been shown to induce toxicity in a wide range of cancer cell lines; using animal models pharmacological ascorbate has shown promise for use in cancer treatment. At pharmacological concentrations the oxidation of ascorbate produces a high flux of H2O2 via the formation of ascorbate radical (Asc•−). The rate of oxidation of ascorbate is principally a function of the level of catalytically active metals. Iron in cell culture media contributes significantly to the rate of H2O2 generation. We hypothesized that increasing intracellular iron would enhance ascorbate-induced cytotoxicity and that iron chelators could modulate the catalytic efficiency with respect to ascorbate oxidation. Treatment of cells with the iron-chelators deferoxamine (DFO) or dipyridyl (DPD) in the presence of 2 mM ascorbate decreased the flux of H2O2 generated by pharmacological ascorbate and reversed ascorbate-induced toxicity. Conversely, increasing the level of intracellular iron by pre-incubating cells with Fe-hydroxyquinoline (HQ) increased ascorbate toxicity and decreased clonogenic survival. These findings indicate that redox metal metals, e.g. Fe3+/Fe2+, have an important role in ascorbate-induced cytotoxicity. Approaches that increase catalytic iron could potentially enhance the cytotoxicity of pharmacological ascorbate in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of labile iron in the toxicity of pharmacological ascorbate

Wagner

Buettner

et al. 2015

Free Radical Biology and Medicine

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“…Hydroxyl radical is considered to be the most notorious reactive oxygen species due to its high reactivity (about 10 9 times less stabile compared to H 2 O 2 )36. However, for the same reason, extracellularly-produced hydroxyl radical is incapable of reaching sensitive intracellular targets18. Most hydroxyl radicals are buffered by extracellular proteins and some by Asc and membrane lipids.…”

Section: Discussionmentioning

confidence: 99%

“…It is important to point out that although plasma and interstitial fluid share very similar redox properties17, the critical in vivo accumulation of H 2 O 2 could take place only in interstitial fluid, as catalase (CAT)-rich erythrocytes buffer H 2 O 2 in the blood. The lack of studies that address the effects of iron at (patho)physiological concentrations is rather perplexing, particularly if we take into account previous findings showing that iron can protect cancer cells from H 2 O 2 18.…”

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confidence: 99%

Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study

Mojić

Pristov

Maksimović‐Ivanić

et al. 2014

Sci Rep

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In vitro studies have shown that hydrogen peroxide (H2O2) produced by high-concentration ascorbate and cell culture medium iron efficiently kills cancer cells. This provided the rationale for clinical trials of high-dose intravenous ascorbate-based treatment for cancer. A drawback in all the in vitro studies was their failure to take into account the in vivo concentration of iron to supplement cell culture media which are characterized by low iron content. Here we showed, using two prostate cancer cell lines (LNCaP and PC-3) and primary astrocytes, that the anticancer/cytotoxic effects of ascorbate are completely abolished by iron at physiological concentrations in cell culture medium and human plasma. A detailed examination of mechanisms showed that iron at physiological concentrations promotes both production and decomposition of H2O2. The latter is mediated by Fenton reaction and prevents H2O2 accumulation. The hydroxyl radical, which is produced in the Fenton reaction, is buffered by extracellular proteins, and could not affect intracellular targets like H2O2. These findings show that anticancer effects of ascorbate have been significantly overestimated in previous in vitro studies, and that common cell culture media might be unsuitable for redox research.

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“…EPR using specific traps is an indispensable tool in studying the metabolism of nitric oxide ( • NO), which represents a radical species that is crucial in a large number of biomedical settings (14,88,92,111). EPR technique for the measurement of • NO is based on its entrapment to form a stable paramagnetic NO-adduct.…”

Section: Epr In Oxidative Status Research -The Detection Of Long Livementioning

confidence: 99%

Electron Paramagnetic Resonance - A Powerful Tool of Medical Biochemistry in Discovering Mechanisms of Disease and Treatment Prospects

Spasojević¹

2010

Journal of Medical Biochemistry

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Electron Paramagnetic Resonance - A Powerful Tool of Medical Biochemistry in Discovering Mechanisms of Disease and Treatment ProspectsIn pathophysiological conditions related to oxidative stress, the application of selected antioxidants could have beneficial effects on human health. Electron paramagnetic resonance (EPR) spectroscopy is a technique that provides unique insight into the redox biochemistry, due to its ability to: (i) distinguish and quantify different reactive species, such as hydroxyl radical, superoxide, carbon centered radicals, hydrogen atom, nitric oxide, ascorbyl radical, melanin, and others; (ii) evaluate the antioxidative capacity of various compounds, extracts and foods; (iii) provide information on other important parameters of biological systems. A combination of EPR spectroscopy and traditional biochemical methods represents an efficient tool in the studies of disease mechanisms and antioxidative therapy prospects, providing a more complete view into the redox processes in the human organism.

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Extracellular Iron(II) Can Protect Cells from Hydrogen Peroxide

Cited by 25 publications

References 9 publications

Role of labile iron in the toxicity of pharmacological ascorbate

Role of labile iron in the toxicity of pharmacological ascorbate

Extracellular iron diminishes anticancer effects of vitamin C: An in vitro study

Electron Paramagnetic Resonance - A Powerful Tool of Medical Biochemistry in Discovering Mechanisms of Disease and Treatment Prospects

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