Natural compounds as heme oxygenase-1 inducers to reduce the deleterious consequences following SARS-CoV-2 infection

2021 ◽  
Vol 15 ◽  
Author(s):  
Valeria Sorrenti ◽  
Valeria Consoli ◽  
Salvo Grosso S. ◽  
Luca Vanella
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Organ Failure ◽  
Heme Oxygenase ◽  
Fruits And Vegetables ◽  
Informed Choice ◽  
Natural Compounds ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
Global Pandemic ◽  
Free Heme

: The virus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) causes COVID 19 (COronaVIrus Disease 19), a global pandemic with multi-organ failure and resulting in high morbidity and mortality. Some individuals are more vulnerable than others and have deleterious consequences following covid- 19. It has been postulated that Heme oxygenase-1 (HO-1) reduction and free heme may contribute to many of the inflammatory phenomena observed in COVID-19 patients. Therefore, HO-1 inducers could prove to be potential therapeutic or preventive agents for COVID 19. Many of the natural compounds present in fruits and vegetables, such as polyphenols, resulted able to induce HO-1. Aim of this review is to focus on the main foods containing bioactive compounds able to induce HO-1 for an informed choice of foods to use to counteract damage from SARS-CoV-2 infection.

Abstract TP102: Modulation of Neuroinflammation by Haptoglobin Reduces Oxidative Stress and Improves ICH Outcomes

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jenna Leclerc ◽  
Alex Dang ◽  
Juan Santiago-Moreno ◽  
Sylvain Dore
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Functional Outcomes ◽  
Ferric Iron ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
Blood Components ◽  
Autologous Whole Blood ◽  
The Brain ◽  
Histological Staining

Intracerebral hemorrhage (ICH) is a stroke subtype associated with high morbidity and mortality. With breakdown of the blood-brain barrier and entry of toxic blood components and metabolites within the brain, a highly oxidative environment ensues and leads to a toxic neuroinflammatory cascade. A major cause of the debilitation following brain hemorrhage is due to the direct toxicity of blood components, notably hemoglobin (Hb), the most upstream precipitating factor in the cascade. The acute phase plasma protein haptoglobin (Hp) binds Hb and inhibits its cytotoxic, pro-oxidative, and pro-inflammatory properties. In this study, we investigated whether the local and specific overexpression of Hp would aid in the safe detoxification and clearance of free Hb, thereby protecting the neuropil from Hb-mediated oxidative stress and improving ICH outcomes. Hp was overexpressed locally within the brain using uniquely designed adeno-associated viral vectors and ICH was induced using the intrastriatal autologous whole blood injection model. Functional outcomes were assessed by a 24-point neurological deficit score. At 72h post-hemorrhage, mice were sacrificed and brains collected for histological staining. Hp-overexpressing mice demonstrated smaller lesion volumes (p<0.05) with less blood accumulation (p<0.05) and improve neurologic status after ICH (p<0.05) when compared to an identically treated control group (n=11-13/group). Histological staining for Iba-1, GFAP, heme oxygenase-1, 4-hydroxynonenal, ferric iron, and myeloperoxidase was performed and revealed: 1) significantly less heme oxygenase-1 expression and lipid peroxidation, 2) a trend towards reduced peripheral neutrophil infiltration, 3) significantly increased cortical microgliosis and cortical and striatal astrogliosis, and 4) no changes in ferric iron content or striatal microgliosis. In conclusion, Hp overexpression in the brain reduces ICH-induced brain injury and improves functional outcomes. Locally modulating brain Hp levels could represent an important clinically relevant strategy for the treatment of ICH.

scholarly journals Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria

2012 ◽  
Vol 80 (4) ◽  
pp. 1445-1454 ◽  
Author(s):  
Vitor R. R. Mendonça ◽  
Nívea F. Luz ◽  
Nadja J. G. Santos ◽  
Valéria M. Borges ◽  
Marilda S. Gonçalves ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Inflammatory Marker ◽  
Plasma Concentrations ◽  
Soluble Form ◽  
Heme Oxygenase 1 ◽  
Asymptomatic Malaria ◽  
Symptomatic Malaria ◽  
Free Heme ◽  
Main Components ◽  
Genetic Profiles

ABSTRACTIntravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of theHMOX1andHpgenes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)nrepeats in the microsatellite polymorphism region of theHMOX1gene, theHp2allele, and theHp2.2genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria.

scholarly journals Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 540 ◽  
Author(s):  
Frank A. D. T. G. Wagener ◽  
Peter Pickkers ◽  
Stephen J. Peterson ◽  
Stephan Immenschuh ◽  
Nader G. Abraham
Keyword(s):  
Critically Ill ◽  
Heme Oxygenase ◽  
Heme Proteins ◽  
Distress Syndrome ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Proof Of Concept ◽  
Effector Molecules ◽  
Free Heme ◽  
Anti Inflammatory

SARS-CoV-2 is causing a pandemic resulting in high morbidity and mortality. COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) are often critically ill and show lung injury and hemolysis. Heme is a prosthetic moiety crucial for the function of a wide variety of heme-proteins, including hemoglobin and cytochromes. However, injury-derived free heme promotes adhesion molecule expression, leukocyte recruitment, vascular permeabilization, platelet activation, complement activation, thrombosis, and fibrosis. Heme can be degraded by the anti-inflammatory enzyme heme oxygenase (HO) generating biliverdin/bilirubin, iron/ferritin, and carbon monoxide. We therefore postulate that free heme contributes to many of the inflammatory phenomena witnessed in critically ill COVID-19 patients, whilst induction of HO-1 or harnessing heme may provide protection. HO-activity not only degrades injurious heme, but its effector molecules possess also potent salutary anti-oxidative and anti-inflammatory properties. Until a vaccine against SARS-CoV-2 becomes available, we need to explore novel strategies to attenuate the pro-inflammatory, pro-thrombotic, and pro-fibrotic consequences of SARS-CoV-2 leading to morbidity and mortality. The heme-HO system represents an interesting target for novel “proof of concept” studies in the context of COVID-19.

Improvement of heme oxygenase-1-based heme sensor for quantifying free heme in biological samples

2015 ◽  
Vol 489 ◽  
pp. 50-52 ◽  
Author(s):  
Junichi Taira ◽  
Yukinori Nakashima ◽  
Shun Yoshihara ◽  
Shinya Koga ◽  
Shinji Sueda ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Biological Samples ◽  
Heme Oxygenase 1 ◽  
Free Heme

Intestinal preconditioning prevents inflammatory response by modulating heme oxygenase-1 expression in endotoxic shock model

2007 ◽  
Vol 293 (6) ◽  
pp. G1308-G1314 ◽  
Author(s):  
Fabienne Tamion ◽  
Vincent Richard ◽  
Sylvanie Renet ◽  
Christian Thuillez
Keyword(s):  
Inflammatory Response ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Heme Oxygenase ◽  
Ischemia Reperfusion ◽  
Multiple Organ ◽  
Intestinal Injury ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Lps Challenge

Gut mucosal injury observed during ischemia-reperfusion is believed to trigger a systemic inflammatory response leading to multiple organ failure. It should be interesting to demonstrate this relationship between gut and multiple organ failure in a sepsis model. Intestinal preconditioning (PC) can be used as a tool to assess the effect of intestinal ischemia in inflammatory response after LPS challenge. The aim of this study was to investigate the protective effect of PC against LPS-induced systemic inflammatory and intestinal heme oxygenase-1 (HO-1) expression. ES was performed with LPS (10 mg/kg iv) with or without PC, which was done before LPS. Rats were first subjected to sham surgery or PC with four cycles of 1 min ischemia and 4 min of reperfusion 24 h before LPS challenge or saline administration. PC significantly reduced fluid requirements, lung edema, intestinal lactate production, and intestinal injury. Inflammatory mRNA expressions for intestine and lung ICAM and TNF were significantly reduced after PC, and these effects were significantly abolished by zinc-protoporphyrin (a specific HO-1 activity inhibitor) and mimicked by bilirubin administration. Intestinal PC selectively increased HO-1 mRNA expression in intestine, but we have observed no expression in lungs. These findings demonstrate that intestinal injury is a important event for inflammatory response and multiple organ injury after LPS challenge. Intestinal HO-1 expression attenuates LPS-induced multiple organ failure by modulating intestine injury and its consequences on inflammatory response. Identification of the exact mechanisms responsible for intestine HO-1 induction may lead to the development of new pharmacological interventions.

scholarly journals Therapeutic Potential of Heme Oxygenase-1 in Aneurysmal Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1150
Author(s):  
Wei-Cheng Jiang ◽  
Chen-Mei Chen ◽  
Candra D. Hamdin ◽  
Alexander N. Orekhov ◽  
Igor A. Sobenin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Vascular Diseases ◽  
High Rate ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
Attractive Option

Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH.

Carbon dots up-regulate heme oxygenase-1 expression towards the acute lung injury therapy

2021 ◽  
Author(s):  
Bo Wang ◽  
Peipei Liu ◽  
Hui Huang ◽  
Xiting Wang ◽  
Mengling Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Carbon Dots ◽  
Morbidity And Mortality ◽  
Heme Oxygenase 1 ◽  
High Morbidity ◽  
A Cell

Pneumonia is a kind of inflammation, which can cause high morbidity and mortality, and the treatment of pneumonia has received widespread attention. Heme oxygenase-1 (HMOX 1) is a cell protective...

scholarly journals Using ultrasound to define the time point of intrauterine growth retardation in a mouse model of heme oxygenase-1 deficiency†

2020 ◽  
Vol 103 (1) ◽  
pp. 126-134 ◽  
Author(s):  
Nicole Meyer ◽  
Stefanie Langwisch ◽  
Markus Scharm ◽  
Ana Claudia Zenclussen
Keyword(s):  
Heme Oxygenase ◽  
Fetal Growth ◽  
Molecular Mechanisms ◽  
Maternal Blood ◽  
Heme Oxygenase 1 ◽  
Intrauterine Growth ◽  
Flow Parameters ◽  
Free Heme ◽  
The Impact

Abstract The enzyme heme oxygenase-1 (HO-1), encoded by the HMOX1 gene, mediates heme catabolism by cleaving free heme. We have previously revealed the importance of HO-1 in pregnancy. Here, we determined the impact of maternal or paternal HO-1 deficiency on fetal growth and placental parameters throughout gestation. We mated Hmox1-sufficient (WT), partial (HET)-, or total (KO)-deficient BALB/c female mice with Hmox1-WT or -KO BALB/c males and performed ultrasound analysis to monitor placental and fetal growth. Doppler measurements were used to determine maternal blood flow parameters. Offspring weights and feto-placental indices (FPI) were also determined. We found a significantly increased number of underdeveloped fetuses at gd10 in HET females that were mated with WT males compared with WT × WT pairings. At the same gestational age, underdeveloped placentas could be detected in HET females mated with KO males. Many fetuses from the KO × KO combination died in utero between gd12 and gd14. At gd14, abnormal placental parameters were found in surviving fetuses, which had significant reduced weights. Moreover, only 3.11% female and 5.33% male KO pups resulted from 10 HET × HET breeding pairs over 1 year. Our results show that HO-1 from both maternal and paternal origins is important for proper placental and fetal growth. Placental growth restriction and occurrence of abortions in mice that were partially or totally deficient in HO-1 were recorded in vivo from gd10 onwards. Future studies will focus on elucidating the cellular and molecular mechanisms behind these observations.

Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease

Blood ◽  
2021 ◽  
Author(s):  
Archita Venugopal Menon ◽  
Jing Liu ◽  
Hanting Phoebe Tsai ◽  
Lingxue Zeng ◽  
Seungjeong Yang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Sickle Cell Disease ◽  
Heme Oxygenase ◽  
Sickle Cell ◽  
Cardiovascular Complications ◽  
Heme Oxygenase 1 ◽  
Cell Disease ◽  
Cardiac Damage ◽  
Downstream Effects ◽  
Free Heme

Sickle cell disease (SCD) is characterized by increased hemolysis which results in plasma heme overload and ultimately cardiovascular complications. Here, we hypothesized that increased heme in SCD causes upregulation of heme oxygenase 1 (Hmox1) which consequently drives cardiomyopathy through ferroptosis, an iron-dependent non-apoptotic form of cell death. First, we demonstrated that the Townes SCD mice had higher levels of hemopexin-free heme in the serum and increased cardiomyopathy, which was corrected by hemopexin supplementation. Cardiomyopathy in SCD mice was associated with upregulation of cardiac Hmox1, and inhibition or induction of Hmox1 improved or worsened cardiac damage, respectively. Since free iron, a product of heme degradation through Hmox1, has been implicated in toxicities including ferroptosis, we evaluated the downstream effects of elevated heme in SCD. Consistent with Hmox1 upregulation and iron overload, levels of lipid peroxidation and ferroptotic markers increased in SCD mice, which were corrected by hemopexin administration. Moreover, ferroptosis inhibitors decreased cardiomyopathy, whereas a ferroptosis inducer erastin exacerbated cardiac damage in SCD and induced cardiac ferroptosis in non-sickling mice. Finally, inhibition or induction of Hmox1 decreased or increased cardiac ferroptosis in SCD mice, respectively. Together, our results identify ferroptosis as a key mechanism of cardiomyopathy in SCD.

scholarly journals Heme oxygenase-1 affords protection against noncerebral forms of severe malaria

2009 ◽  
Vol 106 (37) ◽  
pp. 15837-15842 ◽  
Author(s):  
Elsa Seixas ◽  
Raffaella Gozzelino ◽  
Ângelo Chora ◽  
Ana Ferreira ◽  
Gabriela Silva ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Hepatic Failure ◽  
Parasite Burden ◽  
Heme Oxygenase 1 ◽  
Content Type ◽  
Inflammatory Conditions ◽  
Free Heme ◽  
The One ◽  
Pathogen Burden ◽  
Prosthetic Groups

Infection by Plasmodium, the causative agent of malaria, is associated with hemolysis and therefore with release of hemoglobin from RBC. Under inflammatory conditions, cell-free hemoglobin can be oxidized, releasing its heme prosthetic groups and producing deleterious free heme. Here we demonstrate that survival of a Plasmodium-infected host relies strictly on its ability to prevent the cytotoxic effects of free heme via the expression of the heme-catabolyzing enzyme heme oxygenase-1 (HO-1; encoded by the Hmox1 gene). When infected with Plasmodium chabaudi chabaudi (Pcc), wild-type (Hmox1+/+) BALB/c mice resolved infection and restored homeostasis thereafter (0% lethality). In contrast, HO-1 deficient (Hmox1−/−) BALB/c mice developed a lethal form of hepatic failure (100% lethality), similar to the one occurring in Pcc-infected DBA/2 mice (75% lethality). Expression of HO-1 suppresses the pro-oxidant effects of free heme, preventing it from sensitizing hepatocytes to undergo TNF-mediated programmed cell death by apoptosis. This cytoprotective effect, which inhibits the development of hepatic failure in Pcc-infected mice without interfering with pathogen burden, is mimicked by pharmacological antioxidants such as N-acetylcysteine (NAC). When administered therapeutically, i.e., after Pcc infection, NAC suppressed the development of hepatic failure in Pcc-infected DBA/2 mice (0% lethality), without interfering with pathogen burden. In conclusion, we describe a mechanism of host defense against Plasmodium infection, based on tissue cytoprotection against free heme and limiting disease severity irrespectively of parasite burden.

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