Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes

Aljwaid, H. O.; White, Davinia; Collard, Keith J.; Moody, A. John; Pinkney, Jonathan

doi:10.1016/j.jdiacomp.2015.05.017

Cited by 25 publications

(21 citation statements)

References 40 publications

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“…A subsequent one-electron reduction of ferric to ferrous iron and also producing dehydroascorbate (DHA) can be obtained by oxidation of AFR [4,23]. An alternative mechanism may involve electron transference by tunnelling through the protein via an electron transport chain.…”

Section: Release Of Iron From Ferritinmentioning

confidence: 99%

“…Free "labile" iron activity within body fluids is normally very low and present mainly as hydrated complexes in proteins, such as albumin, or as low molecular weight chelates with citrate or glutathione [2]. In the plasma of patients suffering from iron overload, the amount of redox active and chelatable nontransferrin bound iron (NTBI) is in the range of 1-20 µM [3][4][5]. Ascorbic acid is highly concentrated in a few tissues, e.g.…”

Section: Introductionmentioning

confidence: 99%

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Labile iron potentiates ascorbate-dependent reduction and mobilization of ferritin iron

Badu-Boateng

Pardalaki

Wolf³

et al. 2017

Free Radical Biology and Medicine

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Ascorbate mobilizes iron from equine spleen ferritin by two separate processes. Ascorbate alone mobilizes ferritin iron with an apparent K ≈1.5mM. Labile iron >2μM, complexed with citrate (10mM), synergises ascorbate-dependent iron mobilization by decreasing the apparent K to ≈270μM and raising maximal mobilization rate by ≈5-fold. Catalase reduces the apparent K for both ascorbate and ascorbate+iron dependent mobilization by ≈80%. Iron mobilization by ascorbate alone has a higher activation energy (E=45.0±5.5kJ/mole) than when mediated by ascorbate with labile iron (10μM) (E=13.7±2.2kJ/mole); also mobilization by iron-ascorbate has a three-fold higher pH sensitivity (pH range 6.0-8.0) than with ascorbate alone. Hydrogen peroxide inhibits ascorbate's iron mobilizing action. EPR and autochemiluminescence studies show that ascorbate and labile iron within ferritin enhances radical formation, whereas ascorbate alone produces negligible radicals. These findings suggest that iron catalysed single electron transfer reactions from ascorbate, involving ascorbate or superoxide and possibly ferroxidase tyrosine radicals, accelerate iron mobilization from the ferroxidase centre more than EPR silent, bi-dentate two-electron transfers. These differing modes of electron transference from ascorbate mirror the known mono and bidentate oxidation reactions of dioxygen and hydrogen peroxide with di-ferrous iron at the ferroxidase centre. This study implies that labile iron, at physiological pH, complexed with citrate, synergises iron mobilization from ferritin by ascorbate (50-4000μM). This autocatalytic process can exacerbate oxidative stress in ferritin-containing inflamed tissue.

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Section: Release Of Iron From Ferritinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Labile iron potentiates ascorbate-dependent reduction and mobilization of ferritin iron

Badu-Boateng

Pardalaki

Wolf³

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

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“…Numerous forms of body iron exist, and only forms not bound to transferrin or other iron-binding proteins named non-transferrin-bound iron (NTBI) seem to be implicated in oxidative damages due to their high reactivity [248]. NBTI could be considered a biomarker of the side effect of iron in diseases, greatly correlated with Hb1Ac [249]. Recently, Aljwaid et al [249] confirmed association of NTBI with the risk of vascular complications in diabetes already highlighted 10 years earlier [250,251,252], because NBTI is easily accessible to plaque as well as endothelial cells, macrophages, and smooth muscle cells.…”

Section: Oxidative Stress and Cardiovascular Complicationsmentioning

confidence: 99%

“…NBTI could be considered a biomarker of the side effect of iron in diseases, greatly correlated with Hb1Ac [249]. Recently, Aljwaid et al [249] confirmed association of NTBI with the risk of vascular complications in diabetes already highlighted 10 years earlier [250,251,252], because NBTI is easily accessible to plaque as well as endothelial cells, macrophages, and smooth muscle cells. Inflammation contributes to iron-mediated endothelial dysfunction, characterized by a high release of iron by infiltrated macrophages, an increase in E-selectin, and other adhesion molecules implicated in atherosclerotic plaque [247,253].…”

Section: Oxidative Stress and Cardiovascular Complicationsmentioning

confidence: 99%

The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications

Dal

Sigrist

2016

Diseases

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Obesity and diabetes is generally accompanied by a chronic state of oxidative stress, disequilibrium in the redox balance, implicated in the development and progression of complications such as micro- and macro-angiopathies. Disorders in the inner layer of blood vessels, the endothelium, play an early and critical role in the development of these complications. Blunted endothelium-dependent relaxation and/or contractions are quietly associated to oxidative stress. Thus, preserving endothelial function and oxidative stress seems to be an optimization strategy in the prevention of vascular complications associated with diabetes. Diet is a major lifestyle factor that can greatly influence the incidence and the progression of type 2 diabetes and cardiovascular complications. The notion that foods not only provide basic nutrition but can also prevent diseases and ensure good health and longevity is now attained greater prominence. Some dietary and lifestyle modifications associated to antioxidative supply could be an effective prophylactic means to fight against oxidative stress in diabesity and complications. A significant benefit of phytochemicals (polyphenols in wine, grape, teas), vitamins (ascorbate, tocopherol), minerals (selenium, magnesium), and fruits and vegetables in foods is thought to be capable of scavenging free radicals, lowering the incidence of chronic diseases. In this review, we discuss the role of oxidative stress in diabetes and complications, highlight the endothelial dysfunction, and examine the impact of antioxidant foods, plants, fruits, and vegetables, currently used medication with antioxidant properties, in relation to the development and progression of diabetes and cardiovascular complications.

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“…Measures of hepcidin, NTBI [74][75][76], glycated hemoglobin, insulin resistance, inflammation and possibly other variables were not available in this study. T2D risk may also be attributable to socio-economic factors, environmental contaminants [77][78][79] or Western Lifestyles [80]. These require further investigation of their effects on iron biomarkers and associated iron metabolism.…”

Section: Limitations Of This Studymentioning

confidence: 99%

Ferritin and Percent Transferrin Saturation Levels Predict Type 2 Diabetes Risk and Cardiovascular Disease Outcomes

Zacharski

Shamayeva²,

Chow³

et al. 2017

CDR

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Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes

Abstract: These results support the hypothesis that iron-mediated oxidative stress may be a mechanism linking poor glycaemic control with vascular dysfunction in type 2 diabetes.

Cited by 25 publications

References 40 publications

Labile iron potentiates ascorbate-dependent reduction and mobilization of ferritin iron

Labile iron potentiates ascorbate-dependent reduction and mobilization of ferritin iron

The Protective Effect of Antioxidants Consumption on Diabetes and Vascular Complications

Ferritin and Percent Transferrin Saturation Levels Predict Type 2 Diabetes Risk and Cardiovascular Disease Outcomes

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