Redox Interactions of Vitamin C and Iron: Inhibition of the Pro-Oxidant Activity by Deferiprone.

Autor: Timoshnikov VA; Institute of Chemical Kinetics & Combustion, Novosibirsk zip code: 630090, Russia., Kobzeva TV; Institute of Chemical Kinetics & Combustion, Novosibirsk zip code: 630090, Russia., Polyakov NE; Institute of Chemical Kinetics & Combustion, Novosibirsk zip code: 630090, Russia., Kontoghiorghes GJ; Postgraduate Research Institute of Science, Technology, Environment and Medicine, CY-3504 Limassol, Cyprus.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 May 31; Vol. 21 (11). Date of Electronic Publication: 2020 May 31.
DOI: 10.3390/ijms21113967
Abstrakt: Ascorbic acid (AscH 2 ) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in a medical practice especially for increasing the iron absorption and as an adjuvant therapeutic in the iron chelation therapy, but its mode of action and implications in the iron metabolism and toxicity are not yet clear. In this study, we used UV-Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe 3+ to Fe 2+ , followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe 3+ ↔ Fe 2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron-ascorbate complex compared to the FeL1 3 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL1 3 chelate complex resulting in the formation of mixed L1 2 AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4-5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid , iron, and L1.
Databáze: MEDLINE
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