Abstract
Mangiferin acts as a strong antioxidant on mitochondria. However, when in the presence of Ca2+, mangiferin elicits mitochondrial permeability transition (MPT), as evidenced by cyclosporin A-sensitive mitochondrial swelling. We now provide evidence, by means of electrochemical and UV-visible spectroscopical analysis, that Fe(III) coordinates with mangiferin. The resulting mangiferin-Fe(III) complex does not elicit MPT and prevents MPT by scavenging reactive oxygen species. Indeed, the complex protects mitochondrial membrane protein thiols and glutathione from oxidation. Fe(III) also significantly increases the ability of mangiferin to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical, as well as to display antioxidant activity toward antimycin A-induced H2O2 production and t-butyl hydroperoxide-promoted membrane lipid peroxidation in mitochondria. We postulate that coordination with Fe(III) constitutes a potential protective mechanism toward the prooxidant action of mangiferin and other catechol-containing antioxidants regarding MPT induction. Potential therapeutic relevance of this finding for conditions of pathological iron overload is discussed.
Footnotes
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This work was partially supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, by the Conselho Nacional de Pesquisa, and by a predoctoral fellowship from the Red de Macrouniversidades de América Latina y el Caribe, 2006.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.112003.
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ABBREVIATIONS: ROS, reactive oxygen species; MPT, mitochondrial permeability transition; CsA, cyclosporin A; MDA, malondialdehyde; DPPH, 1,1-diphenyl-2-picrylhydrazyl radical; GSH, reduced glutathione.
- Received August 3, 2006.
- Accepted October 20, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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