-
1.
Tuning the Geometric and Electronic Structure of Synthetic High-Valent Heme Iron(IV)-Oxo Models in the Presence of a Lewis Acid and Various Axial Ligands.
Ehudin, MA, Gee, LB, Sabuncu, S, Braun, A, Moënne-Loccoz, P, Hedman, B, Hodgson, KO, Solomon, EI, Karlin, KD
Journal of the American Chemical Society. 2019;(14):5942-5960
-
-
Free full text
-
Abstract
High-valent ferryl species (e.g., (Por)FeIV═O, Cmpd-II) are observed or proposed key oxidizing intermediates in the catalytic cycles of heme-containing enzymes (P-450s, peroxidases, catalases, and cytochrome c oxidase) involved in biological respiration and oxidative metabolism. Herein, various axially ligated iron(IV)-oxo complexes were prepared to examine the influence of the identity of the base. These were generated by addition of various axial ligands (1,5-dicyclohexylimidazole (DCHIm), a tethered-imidazole system, and sodium derivatives of 3,5-dimethoxyphenolate and imidazolate). Characterization was carried out via UV-vis, electron paramagnetic resonance (EPR), 57Fe Mössbauer, Fe X-ray absorption (XAS), and 54/57Fe resonance Raman (rR) spectroscopies to confirm their formation and compare the axial ligand perturbation on the electronic and geometric structures of these heme iron(IV)-oxo species. Mössbauer studies confirmed that the axially ligated derivatives were iron(IV) and six-coordinate complexes. XAS and 54/57Fe rR data correlated with slight elongation of the iron-oxo bond with increasing donation from the axial ligands. The first reported synthetic H-bonded iron(IV)-oxo heme systems were made in the presence of the protic Lewis acid, 2,6-lutidinium triflate (LutH+), with (or without) DCHIm. Mössbauer, rR, and XAS spectroscopic data indicated the formation of molecular Lewis acid ferryl adducts (rather than full protonation). The reduction potentials of these novel Lewis acid adducts were bracketed through addition of outer-sphere reductants. The oxidizing capabilities of the ferryl species with or without Lewis acid vary drastically; addition of LutH+ to F8Cmpd-II (F8 = tetrakis(2,6-difluorophenyl)porphyrinate) increased its reduction potential by more than 890 mV, experimentally confirming that H-bonding interactions can increase the reactivity of ferryl species.
-
2.
Influence of mitochondrial and systemic iron levels in heart failure pathology.
Lupu, M, Tudor, DV, Filip, GA
Heart failure reviews. 2019;(5):647-659
Abstract
Iron deficiency or overload poses an increasingly complex issue in cardiovascular disease, especially heart failure. The potential benefits and side effects of iron supplementation are still a matter of concern, even though current guidelines suggest therapeutic management of iron deficiency. In this review, we sought to examine the iron metabolism and to identify the rationale behind iron supplementation and iron chelation. Cardiovascular disease is increasingly linked with iron dysmetabolism, with an increased proportion of heart failure patients being affected by decreased plasma iron levels and in turn, by the decreased quality of life. Multiple studies have concluded on a benefit of iron administration, even if just for symptomatic relief. However, new studies field evidence for negative effects of dysregulated non-bound iron and its reactive oxygen species production, with concern to heart diseases. The molecular targets of iron usage, such as the mitochondria, are prone to deleterious effects of the polyvalent metal, added by the scarcely described processes of iron elimination. Iron supplementation and iron chelation show promise of therapeutic benefit in heart failure, with the extent and mechanisms of both prospects not being entirely understood. It may be that a state of decreased systemic and increased mitochondrial iron levels proves to be a useful frame for future advancements in understanding the interconnection of heart failure and iron metabolism.
-
3.
Iron considerations for the athlete: a narrative review.
Sim, M, Garvican-Lewis, LA, Cox, GR, Govus, A, McKay, AKA, Stellingwerff, T, Peeling, P
European journal of applied physiology. 2019;(7):1463-1478
Abstract
Iron plays a significant role in the body, and is specifically important to athletes, since it is a dominant feature in processes such as oxygen transport and energy metabolism. Despite its importance, athlete populations, especially females and endurance athletes, are commonly diagnosed with iron deficiency, suggesting an association between sport performance and iron regulation. Although iron deficiency is most common in female athletes (~ 15-35% athlete cohorts deficient), approximately 5-11% of male athlete cohorts also present with this issue. Furthermore, interest has grown in the mechanisms that influence iron absorption in athletes over the last decade, with the link between iron regulation and exercise becoming a research focus. Specifically, exercise-induced increases in the master iron regulatory hormone, hepcidin, has been highlighted as a contributing factor towards altered iron metabolism in athletes. To date, a plethora of research has been conducted, including investigation into the impact that sex hormones, diet (e.g. macronutrient manipulation), training and environmental stress (e.g. hypoxia due to altitude training) have on an athlete's iron status, with numerous recommendations proposed for consideration. This review summarises the current state of research with respect to the aforementioned factors, drawing conclusions and recommendations for future work.
-
4.
An overview of the relationship between anaemia, iron, and venous leg ulcers.
Ferris, AE, Harding, KG
International wound journal. 2019;(6):1323-1329
-
-
Free full text
-
Abstract
The factors preventing healing in venous leg ulcers are still not fully understood. Iron-mediated tissue damage has been hypothesised, yet anecdotally anaemia is also thought to have a negative effect on wound healing. This article summarises the current evidence for these theories and their likely effects in the context of venous ulceration. A comprehensive search of the literature was conducted. Studies suggest that a number of forms of iron including haemosiderin and ferritin are implicated in progression of venous disease, ulcer formation, and impaired healing, which is thought to be primarily free radical mediated. There is a paucity of evidence for the role of iron deficiency and anaemia on ulcer healing; however, there is likely to be a highly complex interplay between the damaging effects of iron on local tissues and the negative effects of anaemia-mediated tissue hypoxia. Studies looking at options to increase local oxygen delivery such as topical haemoglobin suggest that this may have an impact on some aspects of healing, but findings are generally inconclusive. There is growing evidence that locally elevated iron levels may have a detrimental effect on ulcer healing and formation; however, more robust research is needed.
-
5.
Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.
Rayman, MP
The Proceedings of the Nutrition Society. 2019;(1):34-44
Abstract
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health.
-
6.
Serum Biomarkers of Iron Status and Risk of Primary Liver Cancer: A Systematic Review and Meta-Analysis.
Tran, KT, Coleman, HG, McCain, RS, Cardwell, CR
Nutrition and cancer. 2019;(8):1365-1373
Abstract
Hereditary hemochromatosis, a disease which causes iron overload, has been shown to increase liver cancer risk but the association between serum iron levels within non-hemochromatosis population and liver cancer risk is unclear. We investigated this association by conducting a systematic review and meta-analysis. Medline, Embase, and Scopus were searched to identify articles published up to January 2019. The search incorporated terms for liver cancer (hepatocellular and cholangiocarcinoma) and for serum iron (iron, ferritin, and transferrin). Briefly, nested case-control or cohort studies were included if they recorded a measure of iron, prior to diagnosis, and contained liver cancer patients and controls. Meta-analysis techniques were used to calculate pooled hazard ratios (HRs) and investigate heterogeneity between studies. Nine relevant studies were identified. There was evidence of an association between high serum ferritin and primary liver cancer risk (six studies, HR 1.49, 95% CI 1.13, 1.96) and high serum iron and primary liver cancer risk (three studies, HR 2.47 95% CI 1.31, 4.63). However, these associations were subject to heterogeneity (I2 = 62%, P = 0.02 and I2=80%, P = 0.007, respectively). In conclusion, we found some evidence that increased iron levels was associated with primary liver cancer. The cause of this association merits additional research.
-
7.
Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration.
Masaldan, S, Bush, AI, Devos, D, Rolland, AS, Moreau, C
Free radical biology & medicine. 2019;:221-233
Abstract
Perturbations in iron homeostasis and iron accumulation feature in several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Proteins such as α-synuclein, tau and amyloid precursor protein that are pathologically associated with neurodegeneration are involved in molecular crosstalk with iron homeostatic proteins. Quantitative susceptibility mapping, an MRI based non-invasive technique, offers proximal evaluations of iron load in regions of the brain and powerfully predicts cognitive decline. Further, small molecules that target elevated iron have shown promise against PD and AD in preclinical studies and clinical trials. Despite these strong links between altered iron homeostasis and neurodegeneration the molecular biology to describe the association between enhanced iron levels and neuron death, synaptic impairment and cognitive decline is ill defined. In this review we discuss the current understanding of brain iron homeostasis and how it may be perturbed under pathological conditions. Further, we explore the ramifications of a novel cell death pathway called ferroptosis that has provided a fresh impetus to the "metal hypothesis" of neurodegeneration. While lipid peroxidation plays a central role in the execution of this cell death modality the removal of iron through chelation or genetic modifications appears to extinguish the ferroptotic pathway. Conversely, tissues that harbour elevated iron may be predisposed to ferroptotic damage. These emerging findings are of relevance to neurodegeneration where ferroptotic signalling may offer new targets to mitigate cell death and dysfunction.
-
8.
Integration of nanoscale zero-valent iron and functional anaerobic bacteria for groundwater remediation: A review.
Dong, H, Li, L, Lu, Y, Cheng, Y, Wang, Y, Ning, Q, Wang, B, Zhang, L, Zeng, G
Environment international. 2019;:265-277
Abstract
The technology of integrating nanoscale zero-valent iron (nZVI) and functional anaerobic bacteria has broad prospects for groundwater remediation. This review focuses on the interactions between nZVI and three kinds of functional anaerobic bacteria: organohalide-respiring bacteria (OHRB), sulfate reducing bacteria (SRB) and iron reducing bacteria (IRB), which are commonly used in the anaerobic bioremediation. The coupling effects of nZVI and the functional bacteria on the contaminant removal in the integrated system are summarized. Generally, nZVI could create a suitable living condition for the growth and activity of anaerobic bacteria. OHRB and SRB could synergistically degrade organic halides and remove heavy metals with nZVI, and IRB could reactive the passivated nZVI by reducing the iron (hydr)oxides on the surface of nZVI. Moreover, the roles of these anaerobic bacteria in contaminant removal coupling with nZVI and the degradation mechanisms are illustrated. In addition, this review also discusses the main factors influencing the removal efficiency of contaminants in the integrated treatment system, including nZVI species and dosage, inorganic ions, organic matters, pH, type of pollutants, temperature, and carbon/energy sources, etc. Among these factors, the nZVI species and dosage play a fundamental role due to the potential cytotoxicity of nZVI, which might exert a negative impact on the performance of this integrated system. Lastly, the future research needs are proposed to better understand this integrated technology and effectively apply it in groundwater remediation.
-
9.
Myocardial Performance in Elite Athletes: The Role of Homocysteine, Iron, and Lipids.
Duyuler, S
Medical science monitor : international medical journal of experimental and clinical research. 2019;:1194-1203
Abstract
BACKGROUND The myocardial performance index (MPI) is a comprehensive measure of global systolic and diastolic function of the ventricle, and it has an inverse correlation with maximal oxygen consumption. In this study, the potential association between left ventricle MPI and biochemical biomarkers (including iron, homocysteine, and lipids) in elite athletes was investigated. MATERIAL AND METHODS This cross-sectional observational study consisted of 80 young male elite soccer and basketball players (age: 18-34 years) examined for a seasonal medical check-up. Cardiological examinations and transthoracic echocardiography of these athletes were performed and blood samples were analyzed according to standard laboratory protocols. Tissue Doppler recording was acquired from the mitral annulus using apical 4-chamber view and then the tissue Doppler-derived MPI was computed. RESULTS Athletes were separated into 2 groups based on MPI values (MPI ≤0.40 and MPI >0.40), and baseline demographic, clinical, and biochemical variables of the study participants were compared between these 2 groups. Serum triglyceride, high-density lipoprotein, total cholesterol, homocysteine levels, and iron parameters did not significantly differ between groups, while low-density lipoprotein level was significantly lower in the MPI ≤0.40 group (103.8±26.0 mg/dl vs. 116.8±30.2 mg/dl; p=0.043). Correlation analysis and multivariate linear regression analysis demonstrated a significant association between low-density lipoprotein and MPI. CONCLUSIONS In this study, various biochemical markers were evaluated for possible association with left ventricle MPI as a surrogate of cardiac performance. Among these biomarkers, only low-density lipoprotein was significantly associated with MPI in elite athletes.
-
10.
Iron-Related Factors in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus: the Ma'anshan Birth Cohort (MABC) Study.
Zhu, B, Liang, C, Xia, X, Huang, K, Yan, S, Hao, J, Zhu, P, Gao, H, Tao, F
Biological trace element research. 2019;(1):45-53
Abstract
Iron is an essential micronutrient while its excessive load has been related to the etiology of diabetes. We used data of 3289 pregnant women from the Ma'anshan birth cohort (MABC) study in China to examine the associations of three iron-related factors (i.e., serum iron (SI) concentration, hemoglobin level, and use of iron supplements) with risk of gestational diabetes mellitus (GDM). Emphatically explore the potential non-linear relationship between SI concentration and risk of GDM. SI concentration was measured in fasting blood using inductively coupled plasma mass spectrometry (ICP-MS). GDM diagnosis was determined by 75 g oral glucose tolerance test at 24~28 weeks. Restricted cubic splines with three knots were used to examine potential non-linear relationship between SI concentration and GDM risk. We observed a U-shape relation between SI concentration in the first trimester and risk of GDM. In the multivariate-adjusted model, compared with the middle level (ln(SI), 7.1-7.7 μg/L), both the lowest level (ln(SI) ≤ 7.1 μg/L) (odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.04-1.76) and the highest level (ln(SI) > 7.7 μg/L) (OR = 1.63, 95%CI = 1.16-2.28) increased risk of GDM. Associations of hemoglobin level in the first trimester and risk of GDM attenuated to non-significance after adjustment for pre-pregnancy body mass index (BMI) and blood pressure. Pre-pregnancy iron supplement use was associated with an increased risk of GDM (OR = 1.57, 95%CI = 1.06-2.32). In conclusion, the three iron-related factors are all related to GDM risk on some level.