Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle.
Mangiferin acts as a strong antioxidant on mitochondria. However, when in the presence of Ca(2+), 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 H(2)O(2) 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.
Pardo-Andreu
Gilberto L
GL
Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, Calle 200, Esq. 21, Playa, Ciudad de La Habana, Cuba. g031071@yahoo.com
Cavalheiro
Renata A
RA
Dorta
Daniel J
DJ
Naal
Zeki
Z
Delgado
René
R
Vercesi
Aníbal E
AE
Curti
Carlos
C
D000818:Animals; D004563:Electrochemistry; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D015388:Organelles / Q000187:drug effects*; D010084:Oxidation-Reduction; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D044004:Xanthones; C013592:mangiferin; D007501:Iron; D005978:Glutathione