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.

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 Antidiabetic Potential of the Heme Oxygenase-1 Inducer Curcumin Analogues

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yong Son ◽  
Ju Hwan Lee ◽  
Yong-Kwan Cheong ◽  
Hun-Taeg Chung ◽  
Hyun-Ock Pae
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Heme Oxygenase ◽  
Stress Responses ◽  
Therapeutic Potential ◽  
Heme Oxygenase 1 ◽  
Low Grade ◽  
Cellular Protection ◽  
Inflammatory Stress ◽  
Curcumin Analogues

Although there is a therapeutic treatment to combat diabetes, the identification of agents that may deal with its more serious aspects is an important medical field for research. Diabetes, which contributes to the risk of cardiovascular disease, is associated with a low-grade chronic inflammation (inflammatory stress), oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration of these stresses is critical to the pathogenesis of diabetes, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of diabetic diseases. It has been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular protection. Because HO-1 can reduce oxidative stress, inflammatory stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of diabetes. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in diabetes and present some emerging therapeutic options for HO-1 expression in treating diabetic diseases, together with the therapeutic potential of curcumin analogues that have their ability to induce HO-1 expression.

scholarly journals Involvement of Heme Oxygenase-1 Induction in the Cytoprotective and Immunomodulatory Activities ofViola patriniiin Murine Hippocampal and Microglia Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Li ◽  
Dong-Sung Lee ◽  
Hyun-Gyu Choi ◽  
Kyoung-Su Kim ◽  
Gil-Saeng Jeong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Reactive Oxygen Species Generation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ht22 Cells ◽  
Proinflammatory Mediators ◽  
Bv2 Cells ◽  
Anti Inflammatory

A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract ofViola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-αand interleukin-1β). Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

scholarly journals Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Myrna Constantin ◽  
Alexander J. S. Choi ◽  
Suzanne M. Cloonan ◽  
Stefan W. Ryter
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Heme Oxygenase 1 ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Oxidative Breakdown ◽  
Biliverdin Ix

Heme oxygenase (HO), a catabolic enzyme, provides the rate-limiting step in the oxidative breakdown of heme, to generate carbon monoxide (CO), iron, and biliverdin-IXα. Induction of the inducible form, HO-1, in tissues is generally regarded as a protective mechanism. Over the last decade, considerable progress has been made in defining the therapeutic potential of HO-1 in a number of preclinical models of lung tissue injury and disease. Likewise, tissue-protective effects of CO, when applied at low concentration, have been observed in many of these models. Recent studies have expanded this concept to include chemical CO-releasing molecules (CORMs). Collectively, salutary effects of the HO-1/CO system have been demonstrated in lung inflammation/acute lung injury, lung and vascular transplantation, sepsis, and pulmonary hypertension models. The beneficial effects of HO-1/CO are conveyed in part through the inhibition or modulation of inflammatory, apoptotic, and proliferative processes. Recent advances, however, suggest that the regulation of autophagy and the preservation of mitochondrial homeostasis may serve as additional candidate mechanisms. Further preclinical and clinical trials are needed to ascertain the therapeutic potential of HO-1/CO in human clinical disease.

scholarly journals Association of Heme Oxygenase 1 with the Restoration of Liver Function after Damage in Murine Malaria by Plasmodium yoelii

2014 ◽  
Vol 82 (8) ◽  
pp. 3113-3126 ◽  
Author(s):  
Sumanta Dey ◽  
Somnath Mazumder ◽  
Asim Azhar Siddiqui ◽  
M. Shameel Iqbal ◽  
Chinmoy Banerjee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Function ◽  
Heme Oxygenase ◽  
Tissue Injury ◽  
Parasite Clearance ◽  
Plasmodium Yoelii ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
Suitable Model ◽  
Hepatocyte Apoptosis

ABSTRACTThe liver efficiently restores function after damage induced during malarial infection once the parasites are cleared from the blood. However, the molecular events leading to the restoration of liver function after malaria are still obscure. To study this, we developed a suitable model wherein mice infected withPlasmodium yoelii(45% parasitemia) were treated with the antimalarial α/β-arteether to clear parasites from the blood and, subsequently, restoration of liver function was monitored. Liver function tests clearly indicated that complete recovery of liver function occurred after 25 days of parasite clearance. Analyses of proinflammatory gene expression and neutrophil infiltration further indicated that hepatic inflammation, which was induced immediately after parasite clearance from the blood, was gradually reduced. Moreover, the inflammation in the liver after parasite clearance was found to be correlated positively with oxidative stress and hepatocyte apoptosis. We investigated the role of heme oxygenase 1 (HO-1) in the restoration of liver function after malaria because HO-1 normally renders protection against inflammation, oxidative stress, and apoptosis under various pathological conditions. The expression and activity of HO-1 were found to be increased significantly after parasite clearance. We even found that chemical silencing of HO-1 by use of zinc protoporphyrin enhanced inflammation, oxidative stress, hepatocyte apoptosis, and liver injury. In contrast, stimulation of HO-1 by cobalt protoporphyrin alleviated liver inflammation and reduced oxidative stress, hepatocyte apoptosis, and associated tissue injury. Therefore, we propose that selective induction of HO-1 in the liver would be beneficial for the restoration of liver function after parasite clearance.

scholarly journals The Beneficial Effects of Heme Oxygenase 1 and Hydrogen Sulfide Activation in the Management of Neuropathic Pain, Anxiety- and Depressive-like Effects of Paclitaxel in Mice

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 122
Author(s):  
Gerad Roch ◽  
Gerard Batallé ◽  
Xue Bai ◽  
Enric Pouso-Vázquez ◽  
Laura Rodríguez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Hydrogen Sulfide ◽  
Peripheral Neuropathy ◽  
Heme Oxygenase ◽  
Microglial Activation ◽  
Therapeutic Potential ◽  
Preclinical Model ◽  
Heme Oxygenase 1 ◽  
Pain Anxiety

Chemotherapy-induced peripheral neuropathy constitutes an unresolved clinical problem that severely decreases the quality of the patient’s life. It is characterized by somatosensory alterations, including chronic pain, and a high risk of suffering mental disorders such as depression and anxiety. Unfortunately, an effective treatment for this neuropathology is yet to be found. We investigated the therapeutic potential of cobalt protoporphyrin IX (CoPP), a heme oxygenase 1 inducer, and morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137), a slow hydrogen sulfide (H2S) donor, in a preclinical model of paclitaxel (PTX)-induced peripheral neuropathy (PIPN) in mice. At three weeks after PTX injection, we evaluated the effects of the repetitive administration of 5 mg/kg of CoPP and 35 mg/kg of GYY4137 on PTX-induced nociceptive symptoms (mechanical and cold allodynia) and on the associated emotional disturbances (anxiety- and depressive-like behaviors). We also studied the mechanisms that could mediate their therapeutic properties by evaluating the expression of key proteins implicated in the development of nociception, oxidative stress, microglial activation, and apoptosis in prefrontal cortex (PFC) and dorsal root ganglia (DRG) of mice with PIPN. Results demonstrate that CoPP and GYY4137 treatments inhibited both the nociceptive symptomatology and the derived emotional alterations. These actions were mainly mediated through potentiation of antioxidant responses and inhibiting oxidative stress in the DRG and/or PFC of mice with PIPN. Both treatments normalized some plasticity changes and apoptotic reactions, and GYY4137 blocked microglial activation induced by PTX in PFC. In conclusion, this study proposes CoPP and GYY4137 as good candidates for treating neuropathic pain, anxiety- and depressive-like effects of PTX.

Heme Oxygenase-1 Production by Peripheral Blood Monocytes During Acute Inflammatory Illnesses of Children

2003 ◽  
Vol 228 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Akihiro Yachie ◽  
Tomoko Toma ◽  
Kazunori Mizuno ◽  
Hiroyuki Okamoto ◽  
Shoetsu Shimura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Polymerase Chain Reaction ◽  
Heme Oxygenase ◽  
Tissue Injury ◽  
Heme Oxygenase 1 ◽  
Mrna Levels ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Anti Inflammatory

Monocytes play key roles both in innate and adaptive antigen-specific immunity and they constitute critical components of the immune responses. Although most of the monocyte-derived cytokines exhibit proinflammatory functions in vivo, heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, exerts potent anti-inflammatory effect through production of carbon monoxide and bilirubin. We compared HO-1 production by monocytes in vivo in various acute inflammatory illnesses and in normal controls. Freshly isolated monocytes produced little HO-1 as detected by immunohistochemistry, but it was rapidly induced in vitro upon stimulation. HO-1 production by monocytes was selective because it was not induced in other leukocyte populations, including granulocytes and lymphocytes. Monocytes from acute inflammatory illnesses, such as Kawasaki disease and acute infectious diseases, viral or bacterial, produced significant levels of HO-1, as detected by flow cytometry, immunohistochemistry, and reverse transcription polymerase chain reaction. Quantitative analysis of HO-1 mRNA expression by real-time polymerase chain reaction revealed that monocytes from controls exhibited low, but significant levels of HO-1 mRNA, indicating that circulating monocytes produce HO-1 constantly, in response to basal level of oxidative stress encountered daily. Significantly elevated HO-1 mRNA levels seen in acute inflammatory illnesses suggest that monocyte HO-1 production serve as potent anti-inflammatory agent to control excessive cell or tissue injury in the presence of oxidative stress and cytokinemia.

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

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