Carbon Monoxide in Acute Lung Injury
ABSTRACT Despite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new and effective strategies in order to improve the outcome of these patients. Carbon monoxide, endogenously produced by the heme oxygenase enzyme system, has emerged as promising gaseous therapeutic that exerts protective effects against inflammation, oxidative and mechanical stress, and apoptosis, thus potentially limiting acute lung injury. In this review we discuss the effects of inhaled carbon monoxide on acute lung injury that results from ischemia-reperfusion, transplantation, sepsis, hyperoxia, or mechanical ventilation, the latter referred to as ventilator-induced lung injury. Multiple investigations using in vivo and in vitro models have demonstrated anti-inflammatory, anti-apoptotic, and anti-proliferative properties of carbon monoxide in the lung when applied at low dose prior to or during stressful stimuli. The molecular mechanisms that are modulated by carbon monoxide exposure are still not fully understood. Carbon monoxide mediated lung protection involves several signaling pathways including mitogen activated protein kinases, nuclear factor-κB, activator protein-1, Akt, peroxisome proliferating- activated receptor-γ, early growth response-1, caveolin-1, hypoxia-inducible factor-1α, caspases, Bcl-2-family members, heat shock proteins, or molecules of the fibrinolytic axis. At present, clinical trials on the efficacy and safety of CO investigate whether the promising laboratory findings might be translatable to humans.
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ABSTRACT: Significance: Many reports have underscored the importance of the heme degradation pathway that is regulated by heme oxygenase (HO). This reaction releases bile pigments and carbon monoxide (CO), which are important antioxidant and signaling molecules. Thus, the reaction of HO-1 would have significant cytoprotective effects. Nevertheless, the importance of this protein goes beyond its enzymatic action. New evidence outlines significant effects of inactive forms of the HO-1 protein. Recent advances: In fact, the role of the HO protein in cellular signaling, including transcription factor activation, binding to proteins, phosphorylation, and modulation of protein function, among others, has started being elucidated. The mechanism by which the inducible form of HO-1, in particular, can migrate to various cellular compartments to mediate important signaling or how and why it binds to key transcription factors and other proteins that are important in DNA repair is also described in several physiologic systems. Critical issues: The signaling functions of HO-1 may have particular relevance in clinical circumstances, including cancer, as redistribution of HO-1 into the nuclear compartment is observed with cancer progression and metastasis. In addition, along with oxidative stress, the pleiotropic functions of HO-1 modulate antioxidant defense. In organ transplantation, HO and its byproducts suppress rejection at multiple levels and in sepsis-induced pulmonary dysfunction, inhaled CO or modulation of HO activity can change the course of the disease in animals. Future directions: It is hoped that a more detailed understanding of the various signaling functions of HO will guide therapeutic approaches for complex diseases.Antioxidants & Redox Signaling 11/2013; 20(11). DOI:10.1089/ars.2013.5674 · 7.41 Impact Factor
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ABSTRACT: Ischemia-reperfusion (I/R) physiology, also called reperfusion injury, instigates vascular and tissue injury in human disease states. This review describes why sickle cell anemia should be conceptualized in this fashion and how I/R physiology explains the genesis of characteristic aspects of vascular pathobiology and clinical disease in sickle cell anemia. The nature of I/R and its relevance to sickle cell anemia are discussed, with an emphasis on the acute chest syndrome, endothelial dysfunction with aberrant vasoregulation, circle of Willis vasculopathy, and inflammatory pain. Viewing sickle disease from this perspective elucidates defining pathophysiology and identifies a host of novel potential therapeutic targets.Hematology/oncology clinics of North America 04/2014; 28(2):181-198. DOI:10.1016/j.hoc.2013.11.005 · 2.30 Impact Factor
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ABSTRACT: This study aimed to describe the clinical and socio-demographic aspects of acute poisoning in 2010 in Duzce City, Northwest Anatolian Region of Turkey. Acute poisoning was due to the intentional ingestion of drugs in young and adult people (≥16), who were treated at the Emergency Service of Duzce University Medical Hospital, Turkey from January 1, 2010 to December 31, 2010. In this retrospective and descriptive study, 95 patients were diagnosed with intoxications and 30 of them intentionally ingested drugs to commit suicide. Records of the patients diagnosed with intoxication were obtained from the Clinical Archive of the hospital. Their diagnoses were established according to the International Statistical Classification of Diseases and Related Health Problems. Codes X60-X84 of this classification were used to classify self-infringed drug injuries and drug poisoning. In this series, 35 (36.8%) patients were male and 60 patients (63.2%) female. The male/female ratio was 1.0/1.7. The mean age of the patients was 33.1±14.2 years; 17 (17.9%) patients were below 20 years old and 9 (9.5%) were older than 50 years. Of these patients, 29 (30.5%) were single, 7 (7.4%) divorced or separated, and 59 (62.1%) married. Their mean time for admission to the emergency service after the incident was 208±180 (15-660) minutes. The mean time for admission to the emergency service for patients with food intoxication after the incident was 142±160 minutes, for those with drug intoxication 173±161 minutes, for those with carbon monoxide (CO) intoxication 315±209 minutes, and for those with undefined intoxication 289±166 minutes (P=0.005). Most of the intoxication cases occurred in winter (41.1%, 39 of 95 patients). Admissions to the emergency service were most common in December and April (21 and 16 of 95 patients, respectively). Sixty-five (68.4%) cases were involved in non-deliberate poisoning, whereas 30 (31.6%) were involved in deliberate poisoning. Twenty-six of the 95 patients with acute poisonings had mortality risk at admission, however only one died from CO intoxication in the emergency service (1.1%). Suicide attempts were more common in females than in males (21 of 30 patients, 70%, P<0.05). In Duzce City of Turkey, most intoxication cases occurred in winter, especially in December. They had non-deliberate poisoning, but deliberate poisoning in suicide attempts was more common in females than in males.03/2015; 6(1):54-9. DOI:10.5847/wjem.j.1920-8642.2015.01.010