Iron metabolism in infections: Focus on COVID-19

Girelli, Domenico; Marchi, Giacomo; Busti, Fabiana; Vianello, Alice

doi:10.1053/j.seminhematol.2021.07.001

Cited by 56 publications

(57 citation statements)

References 90 publications

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“…As previously commented, oxidative damage gets aggravated when alterations in iron metabolism are also present [ 47 ]. Iron is transported across the membrane of throphoblasts via the divalent metal transporter DMT1 and released from the basolateral membrane to the bloodstream via FPN.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 during Gestation: Maternal Implications of Evoked Oxidative Stress and Iron Metabolism Impairment

et al. 2022

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COVID-19 has reached pandemic proportions worldwide, with considerable consequences for both health and the economy. In pregnant women, COVID-19 can alter the metabolic environment, iron metabolism, and oxygen supply of trophoblastic cells, and therefore have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the oxidative/antioxidant status in mothers’ serum and placenta, together with placental iron metabolism. Results showed no differences in superoxide dismutase activity and placental antioxidant capacity. However, antioxidant capacity decreased in the serum of infected mothers. Catalase activity decreased in the COVID-19 group, while an increase in 8-hydroxy-2’-deoxyguanosine, hydroperoxides, 15-FT-isoprostanes, and carbonyl groups were recorded in this group. Placental vitamin D, E, and Coenzyme-Q10 also showed to be increased in the COVID-19 group. As for iron-related proteins, an up-regulation of placental DMT1, ferroportin-1, and ferritin expression was recorded in infected women. Due to the potential role of iron metabolism and oxidative stress in placental function and complications, further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in mothers’ and infants’ health.

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Section: Discussionmentioning

confidence: 99%

COVID-19 during Gestation: Maternal Implications of Evoked Oxidative Stress and Iron Metabolism Impairment

et al. 2022

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“…Dysregulation of iron metabolism (i.e., increased plasma levels of ferritin and decreased levels of iron and TF saturation) and anemia are frequently described in COVID-19 patients [ 24 , 37 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ] and are suggested to play a main role in multiorgan failure of severe SARS-CoV-2 infection. In particular, data from observational studies, which have been confirmed in a large meta-analysis, showed that hemoglobin level decreases, particularly in older people, and is negatively associated with comorbidity and severity of the disease [ 65 , 66 , 68 ].…”

Section: Proposed Mechanisms Of Sars-cov-2 Infection and Ferroptosis Inductionmentioning

confidence: 99%

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

et al. 2021

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Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.

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“…Ferroptosis of non-leukocytic cells often results in the release and activation of a different damage-associated molecular pattern (DAMP), triggering the inflammatory responses [32,33]. Because COVID-19 patients suffered from systemic hyper-inflammation, characterized by ROS elevation and cytokine storm, SARS-CoV-2 infection was predicted to involve ferroptosis [34][35][36]. The prediction was also evidenced by the elevated serum iron load in COVID-19 patients, and the decreased GPX4 expression in SARS-CoV-2 infected cells [37][38][39].…”

Section: Introductionmentioning

confidence: 99%

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

Xia

Zhang

You

2021

Viruses

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Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.

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Iron metabolism in infections: Focus on COVID-19

Cited by 56 publications

References 90 publications

COVID-19 during Gestation: Maternal Implications of Evoked Oxidative Stress and Iron Metabolism Impairment

COVID-19 during Gestation: Maternal Implications of Evoked Oxidative Stress and Iron Metabolism Impairment

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

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