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Journal ArticleDOI

The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: Insights into the potential of various iron therapies to induce oxidative and nitrosative stress

TL;DR: The main features of iron metabolism and its complex interplay with O2(*-), H2O2, NO*, and other more reactive compounds derived from these species are summarized and possible underlying mechanisms are proposed.
About: This article is published in Free Radical Biology and Medicine.The article was published on 2013-12-01. It has received 322 citations till now. The article focuses on the topics: Oxidative stress & Iron deficiency.
Citations
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Journal ArticleDOI
03 Jan 2019-Blood
TL;DR: Based on experience with anemia treatment in chronic kidney disease, critical illness, and cancer, finding the appropriate indications for the specific treatment of AI will require improved understanding and a balanced consideration of the contribution of anemia to each patient's morbidity and the impact of anemic treatment on the patient's prognosis in a variety of disease settings.

537 citations

Journal ArticleDOI
TL;DR: It is shown that following L-carnitine ingestion, γ-butyrobetaine (γBB) is produced as an intermediary metabolite by gut microbes at a site anatomically proximal to and at a rate ∼1,000-fold higher than the formation of TMA.

399 citations


Cites background from "The complex interplay of iron metab..."

  • ...Both HF and iron deficiency are associated with increased oxidative stress.(28,29) Because iron plays a central role in the formation and scavenging of reactive oxygen species,(29) low MCHC could be either a contributing factor to increased oxidative in HF or a result of increased oxidative state because of HF, which impairs iron utilization....

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Journal ArticleDOI
TL;DR: The control over iron homeostasis is a central battlefield in host–pathogen interplay influencing the course of an infectious disease in favor of either the mammalian host or the pathogenic invader.
Abstract: Both, mammalian cells and microbes have an essential need for iron, which is required for many metabolic processes and for microbial pathogenicity. In addition, cross-regulatory interactions between iron homeostasis and immune function are evident. Cytokines and the acute phase protein hepcidin affect iron homeostasis leading to the retention of the metal within macrophages and hypoferremia. This is considered to result from a defense mechanism of the body to limit the availability of iron for extracellular pathogens while on the other hand the reduction of circulating iron results in the development of anemia of inflammation. Opposite, iron and the erythropoiesis inducing hormone erythropoietin affect innate immune responses by influencing IFN- mediated (iron) or NF-kB inducible (erythropoietin) immune effector pathways in macrophages. Thus, macrophages loaded with iron lose their ability to kill intracellular pathogens via IFN- mediated effector pathways such as nitric oxide (NO) formation. Accordingly, macrophages invaded by the intracellular bacteria Salmonella enterica serovar Typhimurium increase the expression of the iron export protein ferroportin thereby reducing the availability of iron for intramacrophage bacteria while on the other side strengthening anti-microbial macrophage effector pathways via increased formation of NO or TNF-. In addition, certain innate resistance genes such as natural resistance associated macrophage protein function (Nramp1) or lipocalin-2 exert part of their antimicrobial activity by controlling host and/or microbial iron homeostasis. Consequently, pharmacological or dietary modification of cellular iron trafficking enhances host resistance to intracellular pathogens but may increase susceptibility to microbes in the extracellular compartment and vice versa. Thus, the control over iron homeostasis is a central battlefield in host-pathogen interplay influencing the course of an infectious disease.

250 citations


Cites background from "The complex interplay of iron metab..."

  • ...…by synergistic effects towards anti-microbial radical formation (Mastroeni et al., 2000; Esposito et al., 2003; Papanikolaou and Pantopoulos, 2005; Koskenkorva-Frank et al., 2013) but second, by directly altering immune cell proliferation and anti-microbial immune effector pathways (Nairz et al.,…...

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  • ...These multiple functional aspects of iron are based on its ability to transfer electrons needed during metabolic processes and to catalyze the formation of highly reactive radicals (Papanikolaou and Pantopoulos, 2005; Koskenkorva-Frank et al., 2013)....

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Journal ArticleDOI
TL;DR: A hypothesis based on strong scientific documentation, associating oxidative stress with changes found in patients with COVID-19, such as its participation in the amplification and perpetuation of the cytokine storm, coagulopathy, and cell hypoxia is proposed.

237 citations

Journal ArticleDOI
TL;DR: It is shown that existing regulatory processes are more than adequate to limit the toxicity of iron even in response to iron overload and that intracellular iron is not toxic but a stress responsive programmed cell death-inducing second messenger.

190 citations

References
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Journal ArticleDOI
TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

12,240 citations

Journal ArticleDOI
TL;DR: In this article, the rate constants for over 3500 reaction are tabulated, including reaction with molecules, ions and other radicals derived from inorganic and organic solutes, and the corresponding radical anions, ⋅O− and eaq−, have been critically pulse radiolysis, flash photolysis and other methods.
Abstract: Kinetic data for the radicals H⋅ and ⋅OH in aqueous solution,and the corresponding radical anions, ⋅O− and eaq−, have been critically pulse radiolysis, flash photolysis and other methods. Rate constants for over 3500 reaction are tabulated, including reaction with molecules, ions and other radicals derived from inorganic and organic solutes.

9,887 citations

Journal ArticleDOI
TL;DR: There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Abstract: At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

9,131 citations

Journal ArticleDOI
TL;DR: Current evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion, which is presented in detail in this review.
Abstract: The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

5,514 citations