Toxic Effects Of Carbon Monoxide Research Articles

Risk of lung diseases in patients with previous carbon monoxide poisoning: a nationwide population-based cohort study in the Republic of Korea

Introduction Carbon monoxide poisoning is associated with severe damage to various organs. In this study, we aimed to determine if previous carbon monoxide poisoning was associated with an increased risk of lung diseases. Methods The study population was derived from the National Health Insurance Service database of Korea between 1 January 2002 and 31 December 2021. Adults with carbon monoxide poisoning, with at least one visit to medical facilities between 2002 and 2021, were included. For comparison, an equal number of matched controls with the same index date were selected from the database. Results A total of 28,618 patients with carbon monoxide poisoning and 28,618 matched controls were included in this study. Approximately 42.8 per cent of the patient and control groups were female, with a mean age of 51.3 years. In patients with carbon monoxide poisoning, there was a significant increase in the risk of lung cancer (adjusted hazard ratio, 1.84; 95 per cent confidence interval, 1.42–2.39; P < 0.001), chronic obstructive pulmonary disease (adjusted hazard ratio, 1.60; 95 per cent confidence interval, 1.36–1.89; P < 0.001), pulmonary tuberculosis (adjusted hazard ratio, 1.46; 95 per cent confidence interval, 1.13–1.88; P = 0.003), and non-tuberculous mycobacterial infection (adjusted hazard ratio, 1.54; 95 per cent confidence interval, 1.01–2.36; P = 0.047). Discussion In this retrospective cohort study, previous carbon monoxide poisoning was associated with an increased risk of lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection. Further studies are needed to confirm such an association in other populations and the risk of lung diseases due to the toxic effect of carbon monoxide from different sources. Conclusions Previous carbon monoxide poisoning was associated with an increased risk of lung diseases, but the relative importance of the causes and sources of exposure was not known. The long-term management of survivors of acute carbon monoxide poisoning should include monitoring for lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection.

Prenatal diagnosis of hydranencephaly: a clinical case

Hydranencephaly is a rare abnormality of the central nervous system (CNS) of the fetus, in which the cerebral hemispheres are absent and replaced with cerebrospinal fluid, while the structures of the posterior fossa, thalami and falx cerebri remains normal. The ischemic, hemorrhagic complications, infection of the fetus, the toxic effects of carbon monoxide, butane and genetic abnormalities are potential causes of a hydranencephaly development. The article presents the modern data on the possible causes of the hydranencephaly development, and clinical case of prenatal ultrasound diagnosis of hydranencephaly at 28–29 weeks of gestation, highlighting a specific ultrasound signs of this pathology. The management strategy and genetic testing recommendations are described. The difficulties of differential diagnosis and the key signs of similar disorders are discussed, as well as recommendation for future pregnancy planning.

Methamphetamine and carbon monoxide co-toxicity: an unusual case report and literature review

BackgroundComprehending the toxic effects of substances co-detected in bodily fluids presents a formidable challenge. The combined toxic effect of carbon monoxide and methamphetamine remains a rarely discussed issue within the realm of scholarly literature. The main objective of this research is to delve into the potential intricacies of death mechanisms, unraveling the profound impact of both CO and methamphetamine on the heart.Case presentationThe cause and mechanism of death of a young man with toxic levels of CO–Hb and low-dose methamphetamine in his bloodstream were discussed in conjunction with the literature in this study. Methamphetamine levels of 30 ng/mL (0.03 mg/L) and 25.8% CO–Hb were detected in the blood of a 25-year-old individual who was found dead and without any disease.ConclusionsAlthough the amounts of methamphetamine and CO–Hb in the blood were not in the deadly range, it was determined that death occurred as a result of the combined action of these substances. In the present case, it was considered that death occurred as a result due to the combined cardiac effect of methamphetamine and CO, before the lethal blood CO level was reached.

Carbon monoxide: modern concepts to the treatment of acute poisonings (literature review)

Introduction. Carbon monoxide (CO) is one of the most common causes of chemical injuries and the main toxic factor in the people death in fires. The mechanism of the toxic effect of CO, associated with the formation of carboxyhemoglobin and the development of hypoxia, determines the rapid development of the clinical picture of acute intoxication and the need for emergency first aid and medical care to the poisoned. Material and methods. Literature sources, summarized in the bibliographic databases eLIBRARY.RU, PubMed and Scopus, were the material for analysis. Results. First aid is based on quickly removing the victim from the fire zone or other area with a high concentration of CO and providing him with oxygen as soon as possible. During medical evacuation, it is necessary to carry out continuous inhalation of 80-100% oxygen, to ensure rest and warmth of the victim. In the emergency department of the hospital, oxygen inhalation and maintenance therapy should be continued, clinical and laboratory diagnostic measures aimed at assessing the severity of intoxication, identifying complications and concomitant pathology should be performed. In the case of severe CO poisoning, medical care continues to be provided to the victims in the intensive care unit or in the oxygen-barotherapy unit. The main antidote for CO poisoning is oxygen, which can be used in two versions - normobaric or hyperbaric oxygenation. As a pharmacological antidote to CO, zinc bisvinylimidazole diacetate (acizol) which can accelerate the breakdown of carboxyhemoglobin, improve the oxygen-binding and gas-transport properties of blood, as well as the dissociation of oxyhemoglobin in tissues is used. Along with antidotes, an important role in the treatment of CO poisoning is played by pathogenetic and symptomatic therapy aimed at the prevention and treatment of toxic encephalopathy, brain edema, cognitive dysfunction, toxic myocardiodystrophy and arrhythmia, prevention of pneumonia, correction of the acid-base state, compensation of the energy needs of the body, etc. Conclusion. Further improvement of existing means and methods for the treatment of intoxication, the development and introduction of new antidots into medical practice will increase the effectiveness of therapeutic measures, reduce the number of deaths and disabilities after acute poisoning with carbon monoxide.

Carbon monoxide: mechanism of toxic action, pathogenesis and clinical manifestations of acute intoxication

Introduction. Carbon monoxide (CO) remains one of the most common causes of acute poisoning and death, both in everyday life and in emergency situations, especially in fires.Material and methods. The paper summarizes information about the regulatory effects, mechanisms of toxic action, pathogenesis and clinical picture of intoxication, as well as predictors of the severity of CO poisoning.Results. The main mechanism of the toxic effect of CO is due to its ability to bind to the protohemal iron of hemoglobin (Hb) to form carboxyhemoglobin (HbCO). The toxicity of CO may also be enhanced by impaired functions of the myoglobin of the myocardium and skeletal muscles, mitochondrial cytochrome oxidase, and iron-containing enzymes of the antioxidant system. The leading link in the pathogenesis of acute CO intoxication is a violation of the oxygen transport function of hemoglobin and the associated development of hemic and tissue hypoxia. CO-induced cell and tissue damage due to the induction of mitochondrial dysfunction, oxidative stress, free radical hyperproduction, lipid peroxidation, inflammation, and apoptosis also play a role in the pathogenesis of intoxication.Conclusion. The mechanism of toxic action of CO, associated primarily with the formation of carboxyhemoglobin and the development of hypoxia, determines the clinical manifestations of acute intoxication, which depend on the concentration of CO and the duration of exposure, but are almost always associated with the central nervous system and cardiovascular system.

Cardiorespiratory Toxicity of Biomass Pollutants

Traditional biomass alone accounts for 8.5% of global energy consumption and exclusively covers the energy needs of nearly 3 billion people and 1.2 billion of whom do not yet have access to electricity. The smoke resulting from the combustion of this biomass contains various gases having harmful effects on health. This work aims to evaluate the toxic effects of carbon monoxide, methane and hydrogen sulfide on biochemical and cardiorespiratory parameters of Wistar rats. The complete blood count, C-reactive protein, lipid profile and histology of the lungs are evaluated after subchronic exposure to biomass smoke. The results showed a decrease in red blood cells (p = 0.004), an increase in blood platelets, an increase in C - reactive protein (p = 0.003) and triglycerides (p = 0.0041) and a decrease in HDL (p = 0, 0215) after 28 days of exposure. Exposure to smoke from biomass is therefore a source of alteration of cardiorespiratory parameters.

Akut Karbon Monoksit Zehirlenmesiyle Başvuran Hastaların Laktat Düzeyinin Karboksihemoglobin ve Klinik Bulgularla İlişkisi

Aim: Acute carbon monoxide (CO) poisoning is a potentially mortal, though preventable, condition. Mild poisoning presents with non-specific symptoms, such as fatigue, headache, nausea and vomiting, whereas severe exposure to CO can result in loss of consciousness, coma, and death. The aim of this study was to investigate the utility of lactate and carboxyhemoglobin (COHb) levels in the clinical presentation and treatment of patients with acute CO poisoning. Material and Methods: Data were obtained from the hospital information system and patient files with ICD-10 code “T58: Toxic effects of CO”. The blood parameters and vital signs of patients at admission, causes of poisoning, time to hospital, and Glasgow coma scores during admission were recorded. Within related and relevant complications of CO intoxication and data concerning treatment plans and hospitalization status were recorded. Results: A statistically significant difference was found between COHb and lactate levels of patients who did and did not develop neurological and cardiac complications (p&amp;lt;0.001). Moreover, a statistically significant difference was found in COHb and lactate levels among patients who did or did not receive hyperbaric oxygen therapy, and who were hospitalized or not (p&amp;lt;0.001). As looking for biochemical profile, significant correlations was found between COHb and pH, base excess, and bicarbonate and lactate levels. Conclusion: This study shows that COHb and lactate levels at admission to the emergency department are significant for prognosis, follow-up, and treatment of patients with CO poisoning. Elevated lactate and COHb levels may also found to be associated with neurological and cardiac complications.

Carbon monoxide-triggered health effects: the important role of the inflammasome and its possible crosstalk with autophagy and exosomes.

Carbon monoxide (CO) has long been known as a "silent killer" because of its ability to bind hemoglobin (Hb), leading to reduced oxygen carrying capacity of Hb, which is the main cause of CO poisoning (COP) in humans. Emerging studies suggest that mitochondria is a key target of CO action that can impact key biological processes, including apoptosis, cellular proliferation, inflammation, and autophagy. Despite its toxicity at high concentrations, CO also exhibits cyto- and tissue-protective effects at low concentrations in animal models of organ injury and disease. Specifically, CO modulates the production of pro- or anti-inflammatory cytokines and mediators by regulating the NLRP3 inflammasome. Given that human diseases are strongly associated with inflammation, a deep understanding of the exact mechanism is helpful for treatment. Autophagic factors and inflammasomes interact in various situations, including inflammatory disease, and exosomes might function as the bridge between the inflammasome and autophagy activation. Thus, the interplay among autophagy, mitochondrial dysfunction, exosomes, and the inflammasome may play pivotal roles in the health effects of CO. In this review, we summarize the latest research on the beneficial and toxic effects of CO and their underlying mechanisms, focusing on the important role of the inflammasome and its possible crosstalk with autophagy and exosomes. This knowledge may lead to the development of new therapies for inflammation-related diseases and is essential for the development of new therapeutic strategies and biomarkers of COP.

Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.

Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15-40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of these patients requires the identification of accompanying drug ingestions, especially in the setting of intentional poisoning, fire-related toxic gas exposures, and inhalational injuries. Conventional therapy is limited to normobaric and hyperbaric oxygen, with no available antidotal therapy. Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity. There has been some early success in therapies targeting the downstream inflammatory and oxidative effects of CO poisoning. New methods to directly target the toxic effect of CO, such as CO scavenging agents, are currently under development.

Analysis of hospital admissions due to accidental non-fire-related carbon monoxide poisoning in England, between 2001 and 2010.

BackgroundAccidental non-fire-related (ANFR) carbon monoxide (CO) poisoning is a cause of fatalities and hospital admissions. This is the first study that describes the characteristics of ANFR CO hospital admissions in England.MethodsHospital Episode Statistics (HES) inpatient data for England between 2001 and 2010 were used. ANFR CO poisoning admissions were defined as any mention of ICD-10 code T58: toxic effect of CO and X47: accidental poisoning by gases or vapours, excluding ICD-10 codes potentially related to fires (X00-X09, T20-T32 and Y26).ResultsThere were 2463 ANFR CO admissions over the 10-year period (annual rate: 0.49/100 000); these comprised just under half (48.7%) of all non-fire-related (accidental and non-accidental) CO admissions. There was seasonal variability, with more admissions in colder winter months. Higher admission rates were observed in the north of England. Just over half (53%) of ANFR admissions were male, and the highest rates of ANFR admissions were in those aged >80 years.ConclusionThe burden of ANFR CO poisoning is preventable. The results of this study suggest an appreciable burden of CO and highlight differences that may aid targeting of public health interventions.

Analysis of Hospital Admissions Due to Carbon Monoxide Poisoning in England, between 2001 and 2010

Background Carbon monoxide (CO) is a known cause of hospital admissions from accidental poisoning. There are no studies describing the characteristics of hospital admissions due to CO in England. Aim To describe the epidemiology of CO hospital admissions in England between 2001 and 2010, with a focus on accidental causes, in order to inform the development of a national CO surveillance programme. Methods This study uses all Hospital Episode Statistics (HES) inpatient data for England between 2001 and 2010. An admission for CO poisoning was counted as any mention of ICD-10 code T58: Toxic effect of carbon monoxide which was further investigated by cause and excluding fire-related ICD codes. Results Between 2001 and 2010 we identified 2463 non-fire-related accidental admissions to hospital (246 per year). There was a clear north-south regional divide in England with the highest age-standardised rates of accidental CO admissions in both males and females being the North East (females 0.62, males 0.76 per 100,000 person years) and lowest rates in the East of England (females - 0.33/100,000) and the South East (males - 0.38/100,000). There was a clear pattern of increased accidental admissions in the colder months (November to February) and admissions were lowest among the least deprived (12.2% females, 13.1% males). Conclusions Little is known about the number of hospital admissions due to CO poisoning in England; the results of this study suggest a significant burden of CO with important gender, regional, seasonal and deprivation related differences.

Molecular basis of reduced birth weight in smoking pregnant women: mitochondrial dysfunction and apoptosis.

In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), newborn cord blood mononuclear cells (CBMCs) and placenta were collected from 30 smoking pregnant women and their newborns and classified as moderate and severe smoking groups, and compared to a cohort of 21 non-smoking controls. A biomarker for tobacco consumption (cotinine) was assessed by ELISA (enzyme-linked immunosorbent assay). The following parameters were measured in all tissues: mitochondrial chain complex IV [cytochrome c oxidase (COX)] activity by spectrophotometry, mitochondrial DNA levels by reverse transcription polymerase chain reaction, oxidative stress by spectrophotometric lipid peroxide quantification, mitochondrial mass through citrate synthase spectrophotometric activity and apoptosis by Western blot parallelly confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay in placenta. Newborns from smoking pregnant women presented reduced birth weight by 10.75 percent. Materno-fetal mitochondrial and apoptotic PBMC and CBMC parameters showed altered and correlated values regarding COX activity, mitochondrial DNA, oxidative stress and apoptosis. Placenta partially compensated this dysfunction by increasing mitochondrial number; even so ratios of oxidative stress and apoptosis were increased. A CO-induced mitotoxic and apoptotic fingerprint is present in smoking pregnant women and their newborn, with a lack of filtering effect from the placenta. Tobacco consumption correlated with a reduction in birth weight and mitochondrial and apoptotic impairment, suggesting that both could be the cause of the reduced birth weight in smoking pregnant women.

Carbon Monoxide Exposure Associated with High-risk Features and Intentional Exposure are Infrequently Treated with Hyperbaric Oxygen

Data is conflicting regarding the management of carbon monoxide (CO) poisoned patients. Objective: To determine the emergency department management (ED) of intentional CO poisoned patients regarding hyperbaric oxygen therapy (HBO2), compared to those who are unintentionally exposed. Methodology Design: A multi-center retrospective emergency department cohort study. Population: Consecutive patients presenting to 23 Northeastern United States hospital emergency departments, comprising academic, non-academic, urban, suburban, and rural hospitals with the International Classification of Disease primary diagnosis of “toxic effects CO”. Patients were “a priori” divided into intentional/unintentional and “high-risk” (syncope, serum carboxyhemoglobin level ≥ 20%, change in mental status, cardiac arrest, and/or seizures) or “low-risk” (without the above). Results: “Toxic effects of CO” was diagnosed in 1136 patients, 1026 charts were available for analysis and 52 (4.8%) met inclusion criteria as intentional.Mean age was 40 years (standard deviation (SD) ± 13), for intentional patients. Overall, high risk intoxication was reported in 12% (N = 124/1026) of patients, compared to 50% (N= 26/52) of the intentional patients (p ≤ 0.0001). Mean overall CO level was 7%, compared to an intentional rate of 17% (p ≤ 0.0001). Fifty percent of intentionally exposed high-risk patients received HBO2, while only 36% (N = 45/124) of high-risk patients overall did (p = 0.27). Conclusions: Carbon monoxide poisoned patients with intentional exposures and high-risk clinical features are not more likely to receive HBO2.

A high-performance platinum electrocatalyst loaded on a graphene hydrogel for high-rate methanol oxidation

Platinum (Pt)-based catalysts used in direct methanol fuel cells (DMFCs) usually suffer from low catalytic activity, slow kinetics of methanol oxidation and poor electrochemical stability. This is mainly due to the toxic effect of carbon monoxide and inefficient use of the Pt catalysts. To address these problems, we immobilized Pt nanoparticles with diameters of 4-6 nm onto the three-dimensional (3D) interpenetrating graphene networks (graphene hydrogel or G-Gel) deposited in the micropores of nickel foam (NF). In this Pt/G-Gel/NF composite catalyst, nearly all the Pt nanoparticles are accessible to methanol and can be efficiently used for electrocatalyzation. It showed excellent electrochemical stability and an activity 2.6 times that of a conventional Pt/reduced graphene oxide (Pt/rGO) composite catalyst. Furthermore, the rate of methanol electro-oxidation at the Pt/G-Gel/NF catalyst can be about 27 times that at the Pt/rGO catalyst, making it applicable for fabricating DMFCs with high current and/or power outputs.

Mortality and Hospital Admissions Due to Carbon Monoxide Poisoning in Poland

CO в отношении здоровья очень высокая и выражается тысячами людей, которые теряют жизнь и здоровье вследствие вполне узнанного и теоретически возможного для избежания яда.Objective: The quantitative assessment of the health effects due to carbon monoxide poisoning in Poland, their spatial and temporal distribution as well as their relation to the selected indicators of housing and climatic conditions. Material and methods: The descriptive analysis based on the data from mortality registration of the Central Statistical Office in 2000-2011 and on the data from the Polish General Hospital Morbidity Study managed by the National Institute of Public Health in 2005-2011. Results: Between 331 and 418 deaths due to exposure to gases were registered annually in Poland in 2000-2011. A slight decline of mortality in the period covered by the analysis was observed, but the mortality in Poland was higher than in most of the European countries for which data are available. There were more than two-fold differences in mortality between the regions of Poland. In 20052011, between 2557 and 5026 patients annually were treated for toxic effects of carbon monoxide in hospitals. The monthly number of hospital admissions in winter months (November-March) was 4-7 times higher than in the other part of the year (April-October). Monthly hospital admission rates were highly correlated with ambient air temperature and their increase with the declining temperature was especially clear at mean monthly temperature below 10oC. There were more than five-fold differences in hospital admission rates between the regions. However the associations of the region-specific hospitalization rates with mortality due to CO poisoning or with region-specific indicators of housing conditions were weak. Exposure to smoke, fire and flames was the external cause of 6% of cases hospitalized for treatment of toxic effects of CO. Conclusions: The frequency of carbon monoxide poisoning in Poland is greater than in majority of European countries. There are reasons to assume that the poisonings are most often caused by the escape of carbon monoxide from malfunctioning house equipment and by insufficient ventilation. Health burden of carbon monoxide poisoning in Poland is significant, amounting to thousands of people sick or killed by a well-known and potentially avoidable poison.

Carbon monoxide signaling in human red blood cells: evidence for pentose phosphate pathway activation and protein deglutathionylation.

The biochemistry underlying the physiological, adaptive, and toxic effects of carbon monoxide (CO) is linked to its affinity for reduced transition metals. We investigated CO signaling in the vasculature, where hemoglobin (Hb), the CO most important metal-containing carrier is highly concentrated inside red blood cells (RBCs). By combining NMR, MS, and spectrophotometric techniques, we found that CO treatment of whole blood increases the concentration of reduced glutathione (GSH) in RBC cytosol, which is linked to a significant Hb deglutathionylation. In addition, this process (i) does not activate glycolytic metabolism, (ii) boosts the pentose phosphate pathway (PPP), (iii) increases glutathione reductase activity, and (iv) decreases oxidized glutathione concentration. Moreover, GSH concentration was partially decreased in the presence of 2-deoxyglucose and the PPP antagonist dehydroepiandrosterone. Our MS results show for the first time that, besides Cys93, Hb glutathionylation occurs also at Cys112 of the β-chain, providing a new potential GSH source hitherto unknown. This work provides new insights on the signaling and antioxidant-boosting properties of CO in human blood, identifying Hb as a major source of GSH release and the PPP as a metabolic mechanism supporting Hb deglutathionylation. CO-dependent GSH increase is a new RBC process linking a redox-inactive molecule, CO, to GSH redox signaling. This mechanism may be involved in the adaptive responses aimed to counteract stress conditions in mammalian tissues.

Laser-induced photodissociation of carboxyhemoglobin: An optical method for eliminating the toxic effect of carbon monoxide

We propose and examine an optical method for eliminating the toxic effect of carbon monoxide. The developed method is based on laser-induced photodissociation of carboxyhemoglobin in blood vessels and capillaries. By numerical simulation of the interaction of laser radiation with tissue, we calculate the spectra of the action of carboxyhemoglobin and oxyhemoglobin in cutaneous blood vessels. We show that, despite the sufficiently strong overlap of the action spectra of carboxyhemoglobin and oxyhemoglobin, the substantial difference in the quantum yield values makes it possible to develop an optical method for eliminating the toxic effect of carbon monoxide. We determine the criteria for the efficiency of laser-induced photodissociation of carboxyhemoglobin under direct action on lung alveoli through the skin tissue and intravenously.

Induction of heme oxygenase-1 with hemin attenuates hippocampal injury in rats after acute carbon monoxide poisoning

Carbon monoxide (CO) poisoning is a major cause of brain injury and mortality; delayed neurological syndrome (DNS) is encountered in survivors of acute CO exposure. The toxic effects of CO have been attributed to oxidative stress induced by hypoxia. Heme oxygenase-1 (HO-1) is the inducible heme oxygenase isoform, and its induction acts as an important cellular defense mechanism against oxidative stress, cellular injury and disease. In this study, we examined the functional roles of HO-1 induction in a rat model of CO-exposured hippocampal injury. We report that acute CO exposure produces severe hippocampal injury in rats. However, hemin pretreatment reduced both the CO-induced rise in hippocampal water content and levels of neuronal damage in the hippocampus; survival rates at 24 h were significantly improved. Upregulation of HO-1 by hemin pretreatment resulted in a significant decrease in hippocampal levels of malondialdehyde (MDA), a marker of oxidative stress; levels of pro-apoptotic caspase-3 were also reduced. In contrast, inhibition of HO activity by administration of tin protoporphyrin IX (SnPP, a specific inhibitor of HO) abolished the neuroprotective effects of HO-1 induction. These data suggested that the upregulation of endogenous HO-1 expression therefore plays a pivotal protective role in CO neurotoxicity. Though the precise mechanisms underlying hemin-mediated HO-1 induction and neuroprotection are not known, these may involve the anti-oxidant and anti-apoptotic effects of HO-1 enzyme activity.

Lipid Peroxidation was Involved in the Memory Impairment of Carbon Monoxide-induced Delayed Neuron Damage

Carbon monoxide (CO)-induced delayed neuron damage is the serious complication, but the underlying mechanisms are poorly understood. This study was designed to investigate the time-dependent changes of the lipid peroxidation (malondialdehyde, MDA) and antioxidative status (glutathione, GSH; glutathione peroxidase, GSH-Px; glutathione reductase, GR; and anti-reactive oxygen species anti-ROS) in nerve tissues for the possible mechanisms exploration. Adult rats were treated with CO by peritoneal injection, and sacrificed after day 0, 1, 3, 7, 14 and 21 of treatment. The results showed that the step-down latency progressively shortened while the numbers of error increased. Comparing with the level of day 0, MDA levels in serum, cerebral cortex and hippocampus significantly increased on day 1, 3 and 7. The level of GSH increased firstly but then decreased. The activities of GR, GSH-Px, and anti-ROS decreased in serum, cerebral cortex and hippocampus of rats after day 1, 3, 7, 14 and 21. Thus, we concluded that CO-mediated delayed neuron damage might be associated with elevation of lipid peroxidation and reduction of antioxidative status. The time-dependent changes of lipid peroxidation and antioxidative status in serum, cerebral cortex and hippocampus, at least in part, are involved in the toxic effects of CO poisoning on neuron.

Derivatives of Sodium Boranocarbonate as Novel CO-Releasing Molecules (CO-RMs)

Despite the apparent and well-known toxic effects of carbon monoxide (CO), studies on the intriguing biological roles of this molecule are rapidly emerging. Recent investigations have brought to the limelight various physiological effects of CO which include, among others, vasorelaxation and inhibition of organ rejection after transplantation. The importance of CO in biology can be compared with another gas, nitric oxide (NO), an essential and ubiquitous signalling molecule. This parallelism led to the tantalising concept of using CO for therapeutic purposes wherein compounds that transport and deliver this gas to a target tissue would clearly facilitate both the clinical feasibility and the specificity of CO therapy. Sodium boranocarbonate, Na[H3 BCO2H] (1) was the first water-soluble and non-transition metal containing CO-releasing molecule (CO-RM) to be identified. In order to tune the rate of CO release, we modified 1 and synthesised and characterized various derivatives which release CO under physiological conditions but at rates different from the parent compound 1. The synthesis, structure and CO-releasing properties of ester and amide derivatives of 1 will be presented together with some biological studies carried out with a selection of the compounds.