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

Timoshnikov, Viktor A.; Kobzeva, T. V.; Polyakov, Nikolay E.; Kontoghiorghes, George J.

doi:10.3390/ijms21113967

Cited by 101 publications

(77 citation statements)

References 78 publications

(149 reference statements)

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“…In previous studies, several examples of experimentally detected mixed ligand iron complexes of ascorbic acid, e.g., with phenol-amide and deferiprone, were reported [ 87 , 88 , 89 , 113 ]. Most of these mixed ligand iron complexes were shown to be redox active, but not in the case of deferiprone, which inhibits the pro-oxidant effects of ascorbate/iron [ 87 , 88 , 89 , 113 , 114 ]. Most of the redox active complexes appear to undergo fast interaction with the ascorbate anion to form ternary complexes, in which the ascorbate anion is bound to the Fe 3+ center.…”

Section: Biological Implications Of the Iron Complexes Of Ascorbicmentioning

confidence: 99%

“…Similar properties have been observed in the presence of the iron chelating drugs deferiprone and deferoxamine, and also in the case of lactoferrin, the sister protein of transferrin found in neutrophils and secretions such as milk, tears, etc. [ 20 , 81 , 113 , 124 , 133 , 134 , 135 ]. Subsequently to iron uptake, transferrin transfers Fe 3+ to cells to be stored in ferritin or utilized in the production of haemoglobin and other iron-containing proteins, such as the iron–sulfur proteins [ 1 , 2 , 3 , 39 , 66 , 67 , 126 , 136 , 137 , 138 , 139 , 140 ].…”

Section: Toxicity Implications Of the Interaction Of Iron And Ascomentioning

confidence: 99%

“…Many such pharmacological and toxicological effects can be avoided or minimized by hetero-chronic administration of the individual drugs involved in the interactions. Furthermore, chelators such as deferiprone and deferoxamine can be used as antidotes for preventing the pro-oxidant effects of ascorbic acid [ 20 , 81 , 113 ].…”

Section: Drug Interactions With Ascorbic Acid and Ironmentioning

confidence: 99%

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Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

et al. 2020

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Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vitamin C is its antioxidant activity against reactive oxygen species, which are implicated in many diseases of free radical pathology, including biomolecular-, cellular- and tissue damage-related diseases, as well as cancer and ageing. Ascorbic acid and its metabolites, including the ascorbate anion and oxalate, have metal binding capacity and bind iron, copper and other metals. The biological roles of ascorbate as a vitamin are affected by metal complexation, in particular following binding with iron and copper. Ascorbate forms a complex with Fe3+ followed by reduction to Fe2+, which may potentiate free radical production. The biological and clinical activities of iron, ascorbate and the ascorbate–iron complex can also be affected by many nutrients and pharmaceutical preparations. Optimal therapeutic strategies of improved efficacy and lower toxicity could be designed for the use of ascorbate, iron and the iron–ascorbate complex in different clinical conditions based on their absorption, distribution, metabolism, excretion, toxicity (ADMET), pharmacokinetic, redox and other properties. Similar strategies could also be designed in relation to their interactions with food components and pharmaceuticals, as well as in relation to other aspects concerning personalized medicine.

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Section: Biological Implications Of the Iron Complexes Of Ascorbicmentioning

confidence: 99%

Section: Toxicity Implications Of the Interaction Of Iron And Ascomentioning

confidence: 99%

Section: Drug Interactions With Ascorbic Acid and Ironmentioning

confidence: 99%

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Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

et al. 2020

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“…The interactions of chelators and other biomolecules possessing metal binding ligands with proteins involved in iron and other metal metabolism are very important in the turnover and inhibition/activation of enzymes involved in metabolic pathways associated with normal bodily functions, growth, development and immuno-protection [ 69 , 274 , 275 , 276 , 277 ]. The need for iron by cancer cells and pathogenic microbes make chelation a suitable tool for the design of anticancer and antimicrobial therapeutics [ 241 , 278 ].…”

Section: Future Prospectsmentioning

confidence: 99%

Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

Kontoghiorghes

Kontoghiorghe

2020

Cells

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102

174

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Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology.

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“…For more than 80 years since the discovery of VC, its physiological activities and biological functions have been continuously developed ( King and Waugh, 1932 ; Naidu, 2003 ; Grosso et al, 2013 ; Camarena and Wang, 2016 ). As a result of the strong reducing ability of ascorbic acid, it is an important antioxidant, free radical scavenger, and one of the nutrients for preventing sepsis ( Padh, 1990 ; Timoshnikov et al, 2020 ). By the 1950s, VC was considered to have an anti-cancer effect by participating in the redox reaction to affect the growth of cancer cells and even kill them ( McCormick, 1954 ; Yun et al, 2015 ; De Francesco et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

One-Step Biosynthesis of Vitamin C in Saccharomyces cerevisiae

Zhou

Bi²,

Ding³

et al. 2021

Front. Microbiol.

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Vitamin C (VC) is comprehensively applied in foods, cosmetics, pharmaceuticals, and especially clinical medicine. Nowadays, the industrial production of VC mainly relies on the classic two-step fermentation route, and researchers have explored the way for one-step fermentation of VC in recent years. In this study, a VC biosynthesis pathway that directly produced VC from glucose was reconstructed in Saccharomyces cerevisiae, and the protein engineering and metabolic engineering strategies were adopted to improve it. First, five exogenous modules from Arabidopsis were introduced into the chassis cells by synthetic biology approaches to obtain the strain YLAA harboring VC biosynthesis. In addition, L-galactose dehydrogenase (L-GalDH) and L-galactono-1,4-lactone dehydrogenase (L-GLDH) were fused and expressed in S. cerevisiae cells for the first time, which increased the intracellular VC accumulation by 2.78-fold, reaching 9.97 ± 0.09 mg/L. Through copy number engineering, it was further confirmed that the last step catalyzed by L-GLDH is the rate-limiting step. GDP-L-galactose phosphorylase (GPP) encoded by vtc2 is another rate-limiting enzyme confirmed by GAL1p overexpression results. Finally, by balancing gene expression and cell growth, the highest production strain with overexpressing vtc2 by multicopy plasmids was constructed. The VC accumulation reached 24.94 ± 1.16 mg/L, which was currently the highest production from glucose in S. cerevisiae. The production of the recombinant strain reached nearly 44 mg/L with the exogenous addition of L-galactose or glutathione. The results further emphasized the importance of the step catalyzed by GPP. The investigation provided experience for the efficient biosynthesis of VC and the determination of rate-limiting steps.

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

Cited by 101 publications

References 78 publications

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications

Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

One-Step Biosynthesis of Vitamin C in Saccharomyces cerevisiae

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