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Gossypitrin, A Naturally Occurring Flavonoid, Attenuates Iron-Induced Neuronal and Mitochondrial Damage
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Author
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Abstract
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The disruption of iron homeostasis is an important factor in the loss of mitochondrial function in neural cells, leading to neurodegeneration. Here, we assessed the protective action of gossypitrin (Gos), a naturally occurring flavonoid, on iron-induced neuronal cell damage using mouse hippocampal HT-22 cells and mitochondria isolated from rat brains. Gos was able to rescue HT22 cells from the damage induced by 100 mu M Fe(II)-citrate (EC50 8.6 mu M). This protection was linked to the prevention of both iron-induced mitochondrial membrane potential dissipation and ATP depletion. In isolated mitochondria, Gos (50 mu M) elicited an almost complete protection against iron-induced mitochondrial swelling, the loss of mitochondrial transmembrane potential and ATP depletion. Gos also prevented Fe(II)-citrate-induced mitochondrial lipid peroxidation with an IC50 value (12.45 mu M) that was about nine time lower than that for the tert-butylhydroperoxide-induced oxidation. Furthermore, the flavonoid was effective in inhibiting the degradation of both 15 and 1.5 mM 2-deoxyribose. It also decreased Fe(II) concentration with time, while increasing O-2 consumption rate, and impairing the reduction of Fe(III) by ascorbate. Gos-Fe(II) complexes were detected by UV-VIS and IR spectroscopies, with an apparent Gos-iron stoichiometry of 2:1. Results suggest that Gos does not generally act as a classical antioxidant, but it directly affects iron, by maintaining it in its ferric form after stimulating Fe(II) oxidation. Metal ions would therefore be unable to participate in a Fenton-type reaction and the lipid peroxidation propagation phase. Hence, Gos could be used to treat neuronal diseases associated with iron-induced oxidative stress and mitochondrial damage. |
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Language
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English
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Source (journal)
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Molecules: a journal of synthetic chemistry and natural product chemistry. - Bazel
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Publication
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Bazel
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2021
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ISSN
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1420-3049
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DOI
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10.3390/MOLECULES26113364
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Volume/pages
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26
:11
(2021)
, 17 p.
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Article Reference
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3364
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ISI
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000660366600001
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Pubmed ID
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34199597
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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