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2.
Environ Toxicol Pharmacol ; 67: 117-123, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30818178

RESUMO

This study was designed to investigate the neuroprotective effect of hyperoxygenate hydrogen-rich saline (HOHS) against brain injury induced by carbon monoxide (CO) poisoning in rats. A rat model of CO poisoning was established by administering CO via intraperitoneal injection to male Sprague-Dawley rats. Forty-eight adult male rats were randomly divided into the following groups: normal control group (NG), CO poisoning group (CO), HOS treatment group (hyperoxygenated solution, HOS) and HOHS treatment group (HOHS). After CO poisoning, the carboxyhemoglobin (COHb) contents in the blood of rats in all the CO poisoning groups were increased significantly. However, HOS and HOHS significantly decreased COHb contents, furthermore, the HOHS group had lower COHb contents than the HOS group. Arterial oxygen partial pressure (PaO2) and arterial oxygen saturation (SaO2) results showed that HOS and HOHS could improve the oxygenation of the rats with CO poisoning. Compared with the CO group, the HOS group and the HOHS group had persistently neuroprotective effect on CO-induced brain injury, as assessed by modified neurological severity score (mNSS), furthermore, the HOHS group had better neurological functional recovery than the HOS group. The neuronal apoptosis induced by CO was also evaluated. Except the NG group, all the CO-poisoning groups had varying degrees of neuronal apoptosis. There was lesser degree of neuronal apoptosis in both the HOS group and the HOHS group than that in the CO group. Moreover, the HOHS group had more minor degree of neuronal apoptosis than the HOS group. Compared with the CO group, the free radicals production in the HOS group and the HOHS group were significantly inhibited. In addition, there were significantly difference in the free radicals production between the HOS group and the HOHS group. We could conclude that HOHS exerted a stronger neuroprotective effect against CO-induced brain injury than HOS, and the neuroprotective mechanism of HOHS may be related with inhibition of both neuronal apoptosis and free radicals.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Intoxicação por Monóxido de Carbono/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Solução Salina/uso terapêutico , Soluções/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Intoxicação por Monóxido de Carbono/complicações , Intoxicação por Monóxido de Carbono/metabolismo , Carboxihemoglobina/análise , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Ratos Sprague-Dawley
3.
Mol Med Rep ; 19(2): 1032-1039, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569139

RESUMO

Carbon monoxide (CO) has been shown to induce several cardiovascular abnormalities, as well as necrosis, apoptosis and oxidative stress in the brain. Magnesium sulfate (MS) has been shown to have beneficial activities against hypoxia in the brain. In the present study, the possible protective effects of MS against CO­induced cerebral ischemia were investigated. For this purpose, 25 male Wistar rats were exposed to 3,000 ppm CO for 1 h. The animals were divided into 5 groups (n=5 in each group) as follows: The negative control group (not exposed to CO), the positive control group (CO exposed and treated with normal saline), and 3 groups of CO­exposed rats treated with MS (75, 150 and 300 mg/kg/day) administered intraperitoneally for 5 consecutive days. On the 5th day, the animals were sacrificed and the brains were harvested for the evaluation of necrosis, apoptosis and oxidative stress. Histopathological evaluation revealed that MS reduced the number and intensity of necrotic insults. The Bax/Bcl2 ratio and malondialdehyde (MDA) levels were significantly decreased in a dose­dependent manner in the MS­treated rats compared to the positive control group, while a significant dose­dependent increase in Akt expression, a pro­survival protein, was observed. In addition, MS administration reduced pro­apoptotic indice levels, ameliorated histological insults, favorably modulated oxidative status and increased Akt expression levels, indicating a possible neuroprotective effect in the case of CO poisoning. On the whole, the findings of this study indicate that MS may prove to be useful in protecting against CO­induced cerebral injury.


Assuntos
Lesões Encefálicas/prevenção & controle , Intoxicação por Monóxido de Carbono/prevenção & controle , Monóxido de Carbono/antagonistas & inibidores , Sulfato de Magnésio/farmacologia , Necrose/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Monóxido de Carbono/toxicidade , Intoxicação por Monóxido de Carbono/genética , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/patologia , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Injeções Intraperitoneais , Masculino , Malondialdeído/metabolismo , Necrose/genética , Necrose/metabolismo , Necrose/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
4.
Hum Exp Toxicol ; 38(1): 148-154, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29998771

RESUMO

Carbon monoxide (CO) poisoning is a significant cause of death especially in developing countries. The current study investigated cardioprotective effects of insulin in CO-poisoned rats. Male rats were exposed to 3000 ppm CO for 1 h. Insulin (100 and 120 U/kg intraperitoneally) was immediately administered after CO exposure and on the next 4 days, on a daily basis (a total of 5 doses). On day 5, animals were euthanized, and the hearts were harvested for Western blotting and histopathological studies. The electrocardiograms (ECG) were recorded postexposure to CO and after the completion of insulin treatment period. Histopathological evaluations showed reduction of myocardial necrosis in insulin-treated animals compared to controls. BAX/BCL2 ratio, as a proapoptotic index, was significantly reduced in treatment groups ( p < 0.01). The ECG findings showed no differences among groups; also, compared to control animals, myocardial Akt levels were not markedly affected by insulin. The current study showed that insulin significantly reduces myocardial necrotic and apoptotic indices in CO-poisoned rats.


Assuntos
Intoxicação por Monóxido de Carbono/tratamento farmacológico , Cardiotônicos/uso terapêutico , Insulina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/patologia , Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina/análise , Eletrocardiografia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar
5.
Eur Radiol ; 29(3): 1375-1383, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30143836

RESUMO

PURPOSE: Patients with CO intoxication were demonstrated to exhibit white matter (WM) injuries, changes in substantia nigra, dopamine transporter dysfunctions of striatum and Parkinsonism symptoms. We aimed to investigate the relationship between WM injuries of dopaminergic pathways and dopamine transporter dysfunctions of the striatum in patients with acute CO intoxication using both diffusion kurtosis imaging (DKI) and single photon-emission computed tomography (SPECT). MATERIALS AND METHODS: Seventeen patients with acute CO intoxication and 19 age- and gender-matched healthy subjects were enrolled. DKI data were acquired from all participants and Tc-99m-TRODAT-1 SPECT scan was performed on each patient. DKI datasets were fitted to obtain axial, radial and mean diffusivity, fractional anisotropy, axial, radial and mean kurtosis for voxel-based comparison. In addition, the TRODAT-1 binding ratio of the striatum was calculated using the occipital cortices as a reference. In significant regions, correlational analysis was performed to understand the relationship between DKI indices and TRODAT-1 binding ratio. RESULTS: The results showed that DKI indices were significantly altered in multiple WM regions broadly involving the basal ganglia-thalamocortical circuit and nigrostriatal pathway. The correlation analysis further revealed significant correlations between DKI indices and the TRODAT-1 binding ratio in the nigrostriatal pathway (absolute correlation coefficients ranged from 0.5992 to 0.6950, p<0.05), suggesting that CO-induced early WM injuries were associated with dopamine transporter dysfunctions of striatum. CONCLUSION: We concluded that DKI and Tc-99m-TRODAT-1 SPECT scans were helpful in early detection of global WM injuries associated with dysfunctions of dopamine transporter in patients with acute CO intoxication. KEY POINTS: • Voxel-based diffusion kurtosis imaging analysis was helpful in globally detecting early white matter injuries in patients with acute CO intoxication. • CO-induced early white matter injuries were broadly located in basal ganglia-thalamocortical circuit and nigrostriatal pathway. • Early white matter injuries in dopaminergic pathways were significantly correlated with dopamine transporter dysfunctions of the striatum.


Assuntos
Intoxicação por Monóxido de Carbono/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Compostos de Organotecnécio/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos/farmacologia , Substância Branca/diagnóstico por imagem , Doença Aguda , Adulto , Anisotropia , Intoxicação por Monóxido de Carbono/metabolismo , Feminino , Humanos , Masculino , Compostos Radiofarmacêuticos/farmacologia , Substância Branca/metabolismo
6.
J Med Toxicol ; 14(2): 144-151, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29536431

RESUMO

It is conservatively estimated that 5,000 deaths per year and 20,000 injuries in the USA are due to poisonings caused by chemical exposures (e.g., carbon monoxide, cyanide, hydrogen sulfide, phosphides) that are cellular inhibitors. These chemical agents result in mitochondrial inhibition resulting in cardiac arrest and/or shock. These cellular inhibitors have multi-organ effects, but cardiovascular collapse is the primary cause of death marked by hypotension, lactic acidosis, and cardiac arrest. The mitochondria play a central role in cellular metabolism where oxygen consumption through the electron transport system is tightly coupled to ATP production and regulated by metabolic demands. There has been increasing use of human blood cells such as peripheral blood mononuclear cells and platelets, as surrogate markers of mitochondrial function in organs due to acute care illnesses. We demonstrate the clinical applicability of measuring mitochondrial bioenergetic and dynamic function in blood cells obtained from patients with acute poisoning using carbon monoxide poisoning as an illustration of our technique. Our methods have potential application to guide therapy and gauge severity of disease in poisoning related to cellular inhibitors of public health concern.


Assuntos
Células Sanguíneas/metabolismo , Mitocôndrias/metabolismo , Envenenamento/sangue , Envenenamento/metabolismo , Adulto , Biomarcadores , Intoxicação por Monóxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/metabolismo , Metabolismo Energético , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/ultraestrutura , Pesquisa Médica Translacional
7.
J Appl Physiol (1985) ; 124(3): 761-768, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29357489

RESUMO

Tissue PCO values have not been previously estimated under conditions where the blood carboxyhemoglobin % saturation ([COHb]) is at a normal level or increased. Tissue PCO values are not known for conditions when [COHb] is increased during CO therapy or during CO poisoning. Using a modified Krogh parallel capillary-tissue model, mean tissue PCO was calculated for when [COHb] was 1, 5, 10, and 15% saturation, relevant to CO therapy, and 20, 30, and 40% saturation, relevant to CO poisoning. Calculations were made for the time during which CO was being inhaled, after cessation of CO uptake, and for different O2 extractions from blood flowing in the model capillary. The T1/2 of relevant CO reactions was used in these calculations. When the [COHb] increased to 5 to 10% saturation, mean tissue PCO values increased to 500 to 1,100% of values when the [COHb] was 1% saturation. When the [COHb] increased to 20 to 40% saturation, mean tissue PCO values increased to 2,300 to 5,700% of the 1% saturation value. Results indicate the utility of the modified Krogh model in furthering understanding the physiology of determinants of tissue PCO and should facilitate future studies of in vivo CO binding to different extravascular heme proteins during CO therapy and during CO poisoning. NEW & NOTEWORTHY Tissue PCO levels resulting from carboxyhemoglobin concentrations achieved during CO therapy or during CO poisoning have not been previously estimated. Results published here show that at carboxyhemoglobin levels achieved during CO therapy there are 500 to 1,100% increases in mean tissue PCO values. With carboxyhemoglobin increases associated with toxic effects, there are 2,300 to 5,700% increases in the mean tissue PCO. These differences suggest a basis for understanding the therapeutic and toxic effects of CO.


Assuntos
Intoxicação por Monóxido de Carbono/metabolismo , Monóxido de Carbono/metabolismo , Pulmão/metabolismo , Modelos Biológicos , Monóxido de Carbono/uso terapêutico , Humanos , Pressão Parcial
8.
Brain Res Bull ; 137: 329-337, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29355713

RESUMO

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a difficult-to-manage neurological complication that can severely affect the life quality of patients. Although the central nervous system (CNS) injuries have been reported, the underlying molecular mechanisms are still unclear. Therefore, we established a rat model of DEACMP, applying isobaric tags for a relative and absolute quantification (iTRAQ)-based proteomics approach to identify differentially expressed proteins in cerebral tissue. A total of 170 proteins in the CO exposure groups were identified as differentially changed. Bioinformatics analysis suggested that these proteins are mainly involved in the biological processes, such as energy metabolism and many neurodegenerative diseases. Three proteins, Glial fibrillary acidic protein (GFAP), mitochondrial malate dehydrogenase (MDHM), and isocitrate dehydrogenase [NAD] subunit alpha (IDH3A), were identified as playing important roles in CNS injuries in DEACMP, and were successfully confirmed by immunohistochemistry analysis. Our study not only offers us new insights into the pathophysiological mechanisms of CNS injuries in DEACMP, but also may provide clinicians with important references in early prevention and treatment.


Assuntos
Encefalopatias/etiologia , Encefalopatias/metabolismo , Encéfalo/metabolismo , Intoxicação por Monóxido de Carbono/metabolismo , Proteoma , Animais , Encéfalo/patologia , Encefalopatias/patologia , Encefalopatias/psicologia , Intoxicação por Monóxido de Carbono/patologia , Intoxicação por Monóxido de Carbono/psicologia , Sobrevivência Celular , Biologia Computacional , Modelos Animais de Doenças , Progressão da Doença , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Isocitrato Desidrogenase/metabolismo , Malato Desidrogenase/metabolismo , Masculino , Aprendizagem em Labirinto , Proteômica , Distribuição Aleatória , Ratos Sprague-Dawley , Memória Espacial , Fatores de Tempo
9.
Basic Clin Pharmacol Toxicol ; 122(5): 470-480, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29151273

RESUMO

Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is the most severe and clinically intractable complication that occurs following acute CO poisoning. Unfortunately, the mechanism of DEACMP is still vague. Growing evidence indicates that delayed cerebral damage after CO poisoning is related to oxidative stress, abnormal neuro-inflammation, apoptosis and immune-mediated injury. Our recent report indicated that methylene blue (MB) may be a promising therapeutic agent in the prevention of neuronal cell death and cognitive deficits after transient global cerebral ischaemia (GCI). In this study, we aimed to investigate the potential of MB therapy to ameliorate the signs and symptoms of DEACMP. Rats were exposed to 1000 ppm CO for 40 min. in the first step; CO was then increased to 3000 ppm, which was maintained for another 20 min. The rats were implanted with 7-day release Alzet osmotic mini-pumps subcutaneously under the back skin, which provided MB at a dose of 0.5 mg/kg/day 1 hr after CO exposure. The results showed that MB significantly suppressed oxidative damage and expression of pro-inflammatory factors, including tumour necrosis factor-α and interleukin (IL)-1ß. MB treatment also suitably modulated mitochondrial fission and fusion, which is helpful in the preservation of mitochondrial function. Furthermore, MB dramatically attenuated apoptosis and neuronal death. Lastly, behavioural studies revealed that MB treatment preserved spatial learning and memory in the Barnes maze test. Our findings indicated that MB may have protective effects against DEACMP.


Assuntos
Antídotos/farmacologia , Encefalopatias/prevenção & controle , Região CA1 Hipocampal/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/tratamento farmacológico , Azul de Metileno/farmacologia , Neurônios/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encefalopatias/metabolismo , Encefalopatias/patologia , Encefalopatias/fisiopatologia , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/fisiopatologia , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/fisiopatologia , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Dinâmica Mitocondrial/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Aprendizagem Espacial/efeitos dos fármacos , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
10.
Toxicology ; 394: 63-71, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29223502

RESUMO

Severe poisoning induced by carbon monoxide (CO) at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (OH) production in rat striatum, which is greatly susceptible to inhibitors of NADPH oxidase (NOX), including diphenyleneiodonium (DPI), but not xanthine oxidase. The quantitative real-time PCR confirmed the previous microarray finding that CO at 3000 ppm, but not 1000 ppm, enhanced mRNA expression of dual oxidase 2 (DUOX2), but not DUOX1, in rat striatum, both of which are NOX family members producing reactive oxygen species. However, the protein levels of DUOX2 and DUOX1 were decreased by 3000 ppm CO. The CO-induced OH production was resistant to chelerythrine and SB230580, inhibitors of protein kinase C and p38MAPK, respectively, which are reported to mediate activation of DUOX1 and DUOX2, respectively. Deprivation of Ca2+, which is required for activation of both DUOXs, failed to suppress the CO-induced OH production. The CO-induced OH production was strongly suppressed by EHT1864, an inhibitor of Rac (Ras-related C3 botulinum toxin substrate), which is a factor for activation of NOX1, NOX2 and NOX3 (the role of Rac on Nox3 activation is controversial) as much as that was suppressed by DPI. In addition, EHT1864 in combination with DPI further suppressed the CO-induced OH production. There were no significant changes in the protein levels of NOX1 through NOX4 and Rac1. It is likely that the CO-induced OH production is mediated through the activation of Rac-dependent NOX enzymes, such as Nox1, Nox2, and Nox3.


Assuntos
Intoxicação por Monóxido de Carbono/metabolismo , Corpo Estriado/metabolismo , Oxidases Duais/metabolismo , Radical Hidroxila/metabolismo , Animais , Monóxido de Carbono/administração & dosagem , Intoxicação por Monóxido de Carbono/enzimologia , Intoxicação por Monóxido de Carbono/genética , Intoxicação por Monóxido de Carbono/patologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/enzimologia , Corpo Estriado/patologia , Relação Dose-Resposta a Droga , Oxidases Duais/genética , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
11.
Undersea Hyperb Med ; 44(2): 121-131, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28777902

RESUMO

INTRODUCTION: Acute carbon monoxide (CO) poisoning causes serious health problems such as neuropsychological sequelae. This study aimed to investigate neuronal apoptosis and the effects of hyperbaric oxygen (HBO2) on different regions of the rat hippocampus after CO poisoning. METHODS: 90 mature male Sprague Dawley rats were randomly divided into three groups: the normal control group (NC group), the acute carbon monoxide-poisoned group (CO group) and the hyperbaric oxygen treatment group (HBO2 group). CO exposure included 0, 1, 3, 7, 14 and 21 treatment days, one exposure on the first day, and sacrifice on each of the following days. HBO2 exposure included treatment for 0, 1, 3, 7, 14 and 21 days, daily treatment after CO exposure, and sacrifice after the last HBO2 treatment on each of those days. Hematoxylin-eosin staining, immunohistochemical staining, immunofluorescence staining, and western blot analysis were performed to detect apoptosis in brain tissue samples. RESULTS: MMP-9 and caspase-3 were prominently increased by CO exposure and inhibited by HBO2 in the CA3 region in the hippocampus at one, three and seven days (immunohistochemical staining [IHC]: P ⟨ 0.05). Neu N and the ratio of Bcl-2/ BAX were prominently decreased by CO exposure and rescued by HBO2 in the CA3 region after seven days of treatment (IHC: P ⟨ 0.05). CONCLUSION: These findings indicated that neuronal apoptosis in the rat hippocampus could be induced by acute CO exposure, especially in the CA3 region. HBO2 could effectively inhibit neuronal apoptosis, especially in the CA3 region after seven days of treatment. The application of HBO2 to inhibit MMP-9 and apoptosis may contribute to brain recovery after acute CO poisoning.


Assuntos
Apoptose , Intoxicação por Monóxido de Carbono/complicações , Hipocampo/metabolismo , Hipocampo/patologia , Oxigenação Hiperbárica , Metaloproteinase 9 da Matriz/metabolismo , Neurônios/fisiologia , Animais , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/terapia , Caspase 3/metabolismo , Ativação Enzimática , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
12.
Undersea Hyperb Med ; 44(2): 173-177, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28777908

RESUMO

INTRODUCTION: The carboxyhemoglobin half-life (COHb t1/2) during hyperbaric oxygen (HBO2) is often quoted as 23 minutes, derived from the average of two adult male volunteers breathing HBO2 at 3 atmospheres absolute (ATA). However, the mean COHb t1/2 of 12 male volunteer smokers was 26.3 minutes at 1.58 ATA and in 12 non-intubated carbon monoxide (CO) poisoned patients treated at 3 ATA, was 43 minutes. CASE REPORT: An 81-year old male, poisoned by an improperly ventilated natural gas heater, was intubated for coma, then treated with HBO2. His PaO2/FiO2 = 283 from aspiration. His initial COHb was 34.4%, and 18 minutes before HBO2, 5.9%. After a compression interval of 17 minutes, the COHb measured after 22 minutes at 3 ATA was 3.3%. RESULTS: By exponential decay, his COHb t1/2 before HBO2 was 95 minutes. We estimate the range for COHb t1/2 during compression as 62-81 minutes and for the 3-ATA interval, 58 to 49 minutes, respectively. The mid-point estimate of COHb t1/2 at 3 ATA was 53 minutes. CONCLUSIONS: The COHb t1/2 we calculated is greater than previously reported, but longer in our patient possibly because of concomitant respiratory failure, lung dysfunction, and mechanical ventilation. The often-cited COHb t1/2 of 23 minutes, likely underestimates the actual COHb t1/2 in CO-poisoned patients, especially those with cardiopulmonary dysfunction.


Assuntos
Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/metabolismo , Oxigenação Hiperbárica , Idoso de 80 Anos ou mais , Meia-Vida , Humanos , Masculino , Resultado do Tratamento
13.
Hum Exp Toxicol ; 36(3): 247-255, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27150386

RESUMO

Carbon monoxide (CO) poisoning is a leading cause of toxicity-related mortality and morbidity worldwide. Recent studies focused on CO-induced cardiovascular toxicity. Oxidative stress plays an important role in the pathophysiology of CO toxicity. The aim of this study was to elucidate the relationship between cardiac damage biomarkers and oxidative stress biomarkers in patients with CO-induced cardiotoxicity. This study was carried out on 36 CO-poisoned patients admitted to Zagazig University Hospitals. Forty healthy individuals (age- and sex-matched) were selected as a control group. Clinical examination and electrocardiography (ECG) were performed for CO-poisoned patients. These patients have been investigated for carboxyhaemoglobin percent (COHB%) and cardiac damage biomarkers; cardiac troponin I (cTn-I), heart-type fatty acid-binding protein 3 (H-FABP3). Oxidative stress biomarkers comprising malondialdehyde (MDA), asymmetric dimethylarginine (ADMA), and total antioxidant capacity (TAC) have been also assessed. All biomarkers have been assessed on admission (0 h) and 6 h after treatment of CO-poisoned patients with high-flow oxygen and compared with those of the control groups. ECG findings were abnormal in 31 patients (86.11%), where sinus tachycardia was the commonest finding (58.33%). There was a statistically significant increase of COHB%, MDA, ADMA, and H-FABP3 levels, and a significant decrease of TAC level in CO-poisoned patients compared to controls with no significant changes in cTn-I. Six hours following treatment, all measured parameters were significantly improved except for cTn-I, which was significantly increased when compared with admission status (0 h). Furthermore, H-FABP3 showed a significant positive correlation with COHB%, MDA, ADMA, and a negative correlation with TAC, while cTn-I was significantly correlated with COHB% only. ADMA and MDA seem to be the strongest determinants for the prediction of H-FABP3 changes and hence cardiovascular toxicity. Thus, cardiac damage in patients with CO poisoning could be partially mediated by CO-induced oxidative stress, where H-FABP3 level was directly and strongly associated with MDA and ADMA levels.


Assuntos
Arginina/análogos & derivados , Biomarcadores/metabolismo , Intoxicação por Monóxido de Carbono/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Coração/efeitos dos fármacos , Coração/fisiopatologia , Adulto , Arginina/metabolismo , Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina/metabolismo , Estudos de Casos e Controles , Egito , Eletrocardiografia , Proteína 3 Ligante de Ácido Graxo , Feminino , Humanos , Masculino , Fatores de Risco , Adulto Jovem
15.
Basic Clin Pharmacol Toxicol ; 120(6): 541-549, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27983767

RESUMO

Carbon monoxide (CO) poisoning is one of the leading causes of toxicity-related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of this study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulphoraphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO. We found that CO poisoning could induce advanced cognitive dysfunction, while the mitochondrial ultrastructure of neurons in rats of the CO poisoning group was seriously damaged and mitochondrial membrane potential (ΔΨm) was accordingly reduced by transmission electron microscopy (TEM) and JC-1 fluorescent probe assay. CO poisoning could also increase the expressions of both nuclear factor erythroid 2-related factor 2 (Nrf-2) and thioredoxin-1 (Trx-1) proteins and their mRNA in brain tissue with immunohistochemistry and quantitative PCR (qPCR) techniques. Early administration of either middle-dose or high-dose SFP could efficiently improve mitochondrial structure and function and enhance the antioxidative stress ability, thus exerting a positive effect against brain damage induced by acute CO poisoning.


Assuntos
Encéfalo/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/tratamento farmacológico , Isotiocianatos/farmacologia , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Doença Aguda , Animais , Encéfalo/ultraestrutura , Intoxicação por Monóxido de Carbono/metabolismo , Isotiocianatos/uso terapêutico , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Mitocôndrias/ultraestrutura , Fator 2 Relacionado a NF-E2/fisiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/fisiologia
16.
Eur Rev Med Pharmacol Sci ; 20(13): 2891-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27424991

RESUMO

OBJECTIVE: Carbon monoxide (CO) poisoning is very common worldwide. Despite the fact that CO is known to have cardiotoxic effects, as it has non-specific symptoms; cardiotoxicity could easily be overlooked, especially when troponin is not measured. The present study aimed to evaluate the association between troponin I levels and red cell distribution width (RDW) levels, which can be measured rapidly, easily, and affordably in the Emergency Room (ER). PATIENTS AND METHODS: This single-center observational study included a total of 504 consecutive patients, who presented to the ER due to CO poisoning between January 2011 and June 2015. The diagnosis of CO poisoning was made according to the medical history and carboxyhemoglobin (COHb) level of >5%. Elevated troponin test levels, which measure >0.04 ng/ml for our laboratory, were accepted as positive. RESULTS: Patients (mean age 37±14) were classified into two groups: those who had positive troponin levels (38%) and those that did not. Patients with positive troponin, who were older, had longer CO exposure time and higher creatinine, COHb and RDW levels at the index admission following CO poisoning than patients with negative troponin. In a multivariate logistic regression model with forward stepwise method, age, COHb level, CO exposure time, and RDW (HR=1.681, 95% CI: 1.472-1.934, p<0.001) remained associated with an increased risk of troponin positivity following adjustment for the variables that were statistically significant in the univariate analysis and correlated with RDW. CONCLUSIONS: In patients presenting to the ER with CO poisoning, RDW can be helpful for the risk stratification of troponin positivity.


Assuntos
Intoxicação por Monóxido de Carbono , Troponina I/metabolismo , Intoxicação por Monóxido de Carbono/diagnóstico , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina , Índices de Eritrócitos , Humanos , Valor Preditivo dos Testes
17.
J Neurol Sci ; 360: 161-9, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26723994

RESUMO

Proton magnetic resonance spectroscopy ((1)H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using (1)H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent (1)H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent (1)H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. (1)H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. (1)H-MRS within 1week may be useful for predicting DNS development; (1)H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes.


Assuntos
Encéfalo/metabolismo , Intoxicação por Monóxido de Carbono/metabolismo , Substância Branca/metabolismo , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/patologia , Intoxicação por Monóxido de Carbono/patologia , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Substância Branca/patologia
18.
Drug Chem Toxicol ; 39(4): 375-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26810905

RESUMO

Carbon monoxide (CO) is an odorless, colorless, tasteless and non-irritating by-product of inefficient combustion of hydrocarbon fuels such as motor vehicle exhausted gases. It is the leading cause of mortality in the USA among all unintentional toxicants. Male rats exposed to CO poisoning in the heart has many cardiovascular effects such as, cardiomyopathy, tachycardia, arrhythmias, and ischemia and in severe cases, myocardial infarction (MI) and cardiac arrest. Cardiomyocyte apoptosis is one of the most frequent consequences in the heart. Granulocyte colony stimulating factor (G-CSF) is a cytokine that mobilizes and differentiates granulocytes from stem cells. It can stimulate many anti-apoptotic pathways such as JAK2-STAT3 and PI3-Akt kinases following cardiac ischemia. G-CSF exerts its anti-apoptotic effects through binding to its specific cell surface receptor. The purpose of this study was to elucidate the mechanism of anti-apoptotic effect of G-CSF following CO poisoning. Rats were exposed to CO 1500 or 3000 ppm for 60 min. Animals received G-CSF 100 µg/kg subcutaneously for five consecutive days after CO intoxication. Western blot analysis was used to evaluate the expression of six proteins namely JAK2, p-JAK2, STAT3, p-STAT3, Akt1 and p-Akt1 following G-CSF 100 µg/kg consecutive dose administration after CO poisoning. There was a significant difference between phosphorylated proteins including p-JAK2, p-STAT3 and p-Akt1 in the G-CSF groups and those in control groups and there were not any significant differences in total protein among the groups.


Assuntos
Intoxicação por Monóxido de Carbono/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Janus Quinase 2/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/enzimologia , Intoxicação por Monóxido de Carbono/patologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Injeções Subcutâneas , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Fosforilação , Ratos Wistar
19.
Hum Exp Toxicol ; 35(3): 323-31, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25813961

RESUMO

INTRODUCTION: Carbon monoxide (CO) is a colorless, tasteless, odorless, nonirritant gas and CO poisoning affects all organ systems. AIM: We aimed to detect any possible effects of CO exposure on the argyrophilic nucleolar organizing region (AgNOR)-associated protein synthesis of heart cells and whether there is any relationship between AgNOR protein amount and both carboxyhemoglobin (COHb) level and histopathological evaluation methods used for the detection of damage in heart tissue after CO exposure. MATERIALS AND METHODS: The rats were divided into four groups (control, 1000, 3000, and 5000 ppm), each containing six rats. After CO intoxication, COHb levels were measured and the animals were killed on the 7th day. AgNOR staining was performed in the heart tissue. One hundred nuclei per rat were evaluated, and total AgNOR area/nuclear area and mean AgNOR number were analyzed for each nucleus. The CO exposure groups had significantly higher AgNOR values than the control group (p < 0.0001). According to cardiomyopathy (CMY) scoring methods, the differences between groups 3 and 4 and groups 1 and 2 were significant (p < 0.05). A significant positive correlation between AgNOR values and both CMY and COHb levels were detected. CONCLUSION: The detection of AgNOR protein amount may give information about the CMY levels and be used to detect the CO intoxication levels instead of COHb in later periods.


Assuntos
Antígenos Nucleares/metabolismo , Intoxicação por Monóxido de Carbono/patologia , Miocárdio/patologia , Animais , Intoxicação por Monóxido de Carbono/sangue , Intoxicação por Monóxido de Carbono/metabolismo , Carboxihemoglobina/análise , Masculino , Miocárdio/metabolismo , Ratos Wistar
20.
Brain Res ; 1633: 62-72, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26711852

RESUMO

OBJECTIVE: Delayed neuropsychological sequelae (DNS) are the most common and serious effects of severe carbon monoxide (CO) poisoning, occurring in approximately half of all CO poisoning cases. Growing evidence suggests that oxidative stress and secondary reactions in delayed brain injury are crucial to CO toxicity, similar to ischaemia-reperfusion injury. Exogenous methane plays a protective role in ischaemia-reperfusion injury by affecting key events through anti-oxidant, anti-inflammatory, and anti-apoptosis actions. Our study aimed to explore the potential of exogenous methane to relieve the severity of DNS. METHODS: Thirty-six male Sprague-Dawley (SD) rats were divided into three groups of normal-, CO- and CO plus methane-treated rats. The rats in the latter two groups were exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO exposure, saline or methane saline (10 ml/kg) was intraperitoneally administered to rats in the CO group or the CO plus methane group, respectively. On the ninth day after CO exposure, Morris water maze testing, histological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and immunohistochemical labelling were performed on 6 rats in each group. The remaining 6 rats in each group were used to detect oxidative damage markers, inflammatory cytokines and apoptosis proteins. RESULTS: Methane significantly improved CO-impaired pathological characteristics as well as learning and memory performance. In addition, methane significantly increased the superoxide dismutase (SOD) activity, lowered the CO-increased level of malondialdehyde (MDA) 3-nitrotyrosine (3-NT) and 8-hydroxy-2-deoxyguanosine (8-OHdG), inhibited levels of tumour necrosis factor-α (TNF-α), interleukin 1-ß (IL1-ß) and caspase-3 in the rat cerebral cortex and hippocampus but had no effect on IL-6 levels. CONCLUSION: The hippocampus was the main target of CO-induced alterations in the rat brain compared to the cerebral cortex. Methane treatment protected the rat brain from the harmful effects induced by CO exposure and improved the outcome of DNS through anti-oxidant, anti-inflammatory and anti-apoptosis activities.


Assuntos
Encéfalo/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/patologia , Metano/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Encéfalo/metabolismo , Encéfalo/patologia , Intoxicação por Monóxido de Carbono/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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