Oral carbon monoxide therapy in murine sickle cell disease: Beneficial effects on vaso-occlusion, inflammation and anemia

Belcher, John D.; Gomperts, Edward D.; Nguyen, Julia; Chen, Chunsheng; Abdulla, Fuad; Kiser, Zachary Monroe; Gallo, David; Levy, Howard; Otterbein, Leo E.; Vercellotti, Gregory M.

doi:10.1371/journal.pone.0205194

Cited by 47 publications

(42 citation statements)

References 33 publications

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“…Furthermore, CO-saturated solutions provides a straightforward vehicle for both acute and chronic administration. We previously reported that brief local delivery of a saturated solution of CO blocks neointima formation in injured rat arteries, while sustained ingestion of an oral formulation of CO decreases vaso-occlusion and inflammation in murine sickle cell disease [76,160].…”

Section: Therapeutic Potential Of Ho-1 and Its Products In Vascular Rmentioning

confidence: 99%

Targeting Heme Oxygenase-1 in the Arterial Response to Injury and Disease

Durante¹

2020

Antioxidants

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Heme oxygenase-1 (HO-1) catalyzes the degradation of heme into carbon monoxide (CO), iron, and biliverdin, which is rapidly metabolized to bilirubin. The activation of vascular smooth muscle cells (SMCs) plays a critical role in mediating the aberrant arterial response to injury and a number of vascular diseases. Pharmacological induction or gene transfer of HO-1 improves arterial remodeling in animal models of post-angioplasty restenosis, vascular access failure, atherosclerosis, transplant arteriosclerosis, vein grafting, and pulmonary arterial hypertension, whereas genetic loss of HO-1 exacerbates the remodeling response. The vasoprotection evoked by HO-1 is largely ascribed to the generation of CO and/or the bile pigments, biliverdin and bilirubin, which exert potent antioxidant and anti-inflammatory effects. In addition, these molecules inhibit vascular SMC proliferation, migration, apoptosis, and phenotypic switching. Several therapeutic strategies are currently being pursued that may allow for the targeting of HO-1 in arterial remodeling in various pathologies, including the use of gene delivery approaches, the development of novel inducers of the enzyme, and the administration of unique formulations of CO and bilirubin.

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Section: Therapeutic Potential Of Ho-1 and Its Products In Vascular Rmentioning

confidence: 99%

Targeting Heme Oxygenase-1 in the Arterial Response to Injury and Disease

Durante¹

2020

Antioxidants

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“…HOs convert heme into biliverdin, CO, and iron. In the past decades, CO has gained a lot of interest not only by its potential toxicity but also its remarkable cytoprotectant properties against inflammation [95,96], acute lung injury, atherosclerosis [97], or in organ transplantation [98]. This fueled the development of suitable CO delivery systems, such as CO-releasing molecules (CORMs).…”

Section: Carbon Monoxidementioning

confidence: 99%

Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders—Interaction between the Heme Oxygenase and H2S-Producing Systems

Gáll

Pethő

Nagy

et al. 2020

IJMS

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Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H2S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H2S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic/hemorrhagic human diseases, and the potential beneficial role of CO and H2S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic/hemorrhagic diseases through heme oxygenase-1/CO as well as H2S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.

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“…132 Later, other permutations including enzyme-controlled release, 169,170 encapsulated metal-based CO-RMs, [171][172][173][174][175] and photosensitive organic CO-RMs [176][177][178][179][180] were developed. There are also oral forms of CO in a solution being developed by Hillhurst Biopharmaceuticals, 181 and organic CO-RMs that require light for activation. 177,180,182 Most recently, Wang's lab developed several hundreds of organic CO prodrugs belonging to different structural classes 133,149,156,183 that have diverse delivery properties including tunable CO release rates, [184][185][186] triggered release (pH-, 185 esterase-, 184,187 and ROS-sensitive 188 ), mitochondriontargeting, 121 dual-triggers, 183,187 and delivering more than one payload using a single prodrug.…”

Section: Carbon Monoxide Deliverymentioning

confidence: 99%

“…In addition to gaseous CO, metal-based CO-RMs, and the organic CO prodrugs, there are also other forms of CO delivery. For example, Hillhurst Biopharmaceuticals developed a proprietary CO oral formulation, which has shown efficacy in various animal models 181 including kidney IRI and sickle cell disease. 54 As mentioned earlier, ProLong Pharmaceuticals has studied the use of pegylated bovine hemoglobin for delivering CO (www.clinicaltrials.gov).…”

Section: Others Forms Of Co Deliverymentioning

confidence: 99%

Carbon monoxide: An emerging therapy for acute kidney injury

Yang

Caestecker

Otterbein

et al. 2019

Medicinal Research Reviews

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Treating acute kidney injury (AKI) represents an important unmet medical need both in terms of the seriousness of this medical problem and the number of patients. There is also a large untapped market opportunity in treating AKI. Over the years, there has been much effort in search of therapeutics with minimal success. However, over the same time period, new understanding of the underlying pathobiology and molecular mechanisms of kidney injury have undoubtedly helped the search for new therapeutics. Along this line, carbon monoxide (CO) has emerged as a promising therapeutic agent because of its demonstrated cytoprotective, and immunomodulatory effects. CO has also been shown to sensitize cancer, but not normal cells, to chemotherapy. This is particularly important in treating cisplatin-This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

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Oral carbon monoxide therapy in murine sickle cell disease: Beneficial effects on vaso-occlusion, inflammation and anemia

Cited by 47 publications

References 33 publications

Targeting Heme Oxygenase-1 in the Arterial Response to Injury and Disease

Targeting Heme Oxygenase-1 in the Arterial Response to Injury and Disease

Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders—Interaction between the Heme Oxygenase and H2S-Producing Systems

Carbon monoxide: An emerging therapy for acute kidney injury

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