Iron Homeostasis in the Lungs—A Balance between Health and Disease

Neves, Joana; Haider, Thomas; Gassmann, Max; Muckenthaler, Martina U.

doi:10.3390/ph12010005

Cited by 68 publications

(63 citation statements)

References 223 publications

(291 reference statements)

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“…It is well-known that iron, ROS, and inflammation are interconnected, and excessive free iron generated through iron dysregulation or breakdown of iron-metalloproteins may exacerbate disease progression and severity through Fenton-generated ROS (that is the Fe 2+ -dependent production of • OH from H 2 O 2 ), in turn promoting further inflammation [ 76 ]. Disruption of iron homeostasis is known to be a contributing factor in many disorders of the brain, liver, kidneys, and, in particular, the lungs, including ARDS, whereby the excess free iron contributes to oxidative stress and further inflammation if left unchecked [ 76 , 90 , 192 , 193 ]. Indeed, elevated levels of total iron and non-haem iron were seen in the bronchoalveolar lavage fluid of ARDS patients compared to healthy controls [ 90 ].…”

Section: How Might Ergothioneine Be Beneficial In Alleviating Covimentioning

confidence: 99%

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Cheah

Halliwell

2020

Antioxidants

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Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally. Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure. Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine. Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others. When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19. We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions. This review presents evidence to support that proposal.

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Section: How Might Ergothioneine Be Beneficial In Alleviating Covimentioning

confidence: 99%

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Cheah

Halliwell

2020

Antioxidants

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“…Iron participates in the differentiation and growth of epithelial tissue and the production of reactive oxygen species, which combat pathogens [58]. Supplementary iron intake has been found to reduce respiratory infections [122] while pulmonary iron modulation represents a defensive mechanism against various respiratory pathogens [123]. Despite the important role of iron in the immune system, iron-containing enzymes are essential for the replication of coronavirus [124] and the chelation of iron compounds may prove beneficial [37].…”

Section: Zinc Copper Magnesium and Ironmentioning

confidence: 99%

Micronutrients, Non-Nutrients and Mediterranean Diet: A Potential Protective Role Against COVID-19 through Modulation of PAF Actions and Metabolism

Detopoulou¹,

Demopoulos²,

Antonopoulou³

2020

Preprint

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The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, minerals), phytonutrients and Mediterranean diet compounds (olive oil, fish, honey, plant foods) with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/ or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, although there is no single food to prevent coronavirus, the aim is to follow a healthy diet containing PAF inhibitors in order to target both inflammation and thrombosis and try to avoid or/and reduce the deleterious effects of the COVID-19 epidemic.

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“…Similarly, altered iron metabolism was also described in multiple pulmonary diseases including chronic obstructive pulmonary disease (COPD). In the latter one, levels of iron and iron-binding proteins in the lung are increased with normal to reduced systemic iron availability [21,22,23,24]. Moreover, elevated levels of systemic iron are toxic to the lungs and correlate with disease severity and worsening lung function [25,26].…”

Section: Introductionmentioning

confidence: 99%

Mild Iron Overload as Seen in Individuals Homozygous for the Alpha-1 Antitrypsin Pi*Z Variant Does Not Promote Liver Fibrogenesis in HFE Knockout Mice

Güldiken

Hamesch

Schuller

et al. 2019

Cells

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The presence of the homozygous ‘Pi*Z’ variant of alpha-1 antitrypsin (AAT) (‘Pi*ZZ’ genotype) predisposes to liver fibrosis development, but the role of iron metabolism in this process remains unknown. Therefore, we assessed iron metabolism and variants in the Homeostatic Iron Regulator gene (HFE) as the major cause of hereditary iron overload in a large cohort of Pi*ZZ subjects without liver comorbidities. The human cohort comprised of 409 Pi*ZZ individuals and 254 subjects without evidence of an AAT mutation who were recruited from ten European countries. All underwent a comprehensive work-up and transient elastography to determine liver stiffness measurements (LSM). The corresponding mouse models (Pi*Z overexpressors, HFE knockouts, and double transgenic [DTg] mice) were used to evaluate the impact of mild iron overload on Pi*Z-induced liver injury. Compared to Pi*Z non-carriers, Pi*ZZ individuals had elevated serum iron, transferrin saturation, and ferritin levels, but relevant iron overload was rare. All these parameters were higher in individuals with signs of significant liver fibrosis (LSM ≥ 7.1 kPa) compared to those without signs of significant liver fibrosis. HFE knockout and DTg mice displayed similar extent of iron overload and of fibrosis. Loss of HFE did not alter the extent of AAT accumulation. In Pi*ZZ individuals, presence of HFE mutations was not associated with more severe liver fibrosis. Taken together, Pi*ZZ individuals display minor alterations in serum iron parameters. Neither mild iron overload seen in these individuals nor the presence of HFE mutations (C282Y and H63D) constitute a major contributor to liver fibrosis development.

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Iron Homeostasis in the Lungs—A Balance between Health and Disease

Cited by 68 publications

References 223 publications

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

Micronutrients, Non-Nutrients and Mediterranean Diet: A Potential Protective Role Against COVID-19 through Modulation of PAF Actions and Metabolism

Mild Iron Overload as Seen in Individuals Homozygous for the Alpha-1 Antitrypsin Pi*Z Variant Does Not Promote Liver Fibrogenesis in HFE Knockout Mice

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