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Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.

ABSTRACT: Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, while the fact that CO accumulation in tissues is the most likely direct cause of mortality is less investigated. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was used in vivo as a CO removal agent, showing that it acts as an effective adjuvant to O₂ ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning.

SUBMITTER: Mao Q

PROVIDER: S-EPMC8007703 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionExposure to carbon monoxide (CO) is among the most common causes of acute and chronic poisonings worldwide. The crucial point of treatment of such acute poisonings is to eliminate CO from the body as fast as possible. There are currently two approaches to the management of the CO intoxication: hyperbaric oxygen therapy (HOT) and normobaric oxygen therapy (NOT). HOT is highly effective and capable of achieving the CO elimination half-time (T½) as low as 15 minutes. Unfortunately this method is expensive and not always readily available. The elimination of CO with the use of NOT (T½~70 min) is slower, but treatment can be started even on the site of the exposure and continued while the patient is transported to a hospital. The aim of the study was to evaluate the effectiveness of a method using therapeutic hyperventilation with maintenance of isocapnia (IH) in the elimination of CO in volunteers exposed to CO and to compare selected gasometric and respiratory parameters during IH with the values obtained during hyperventilation with pure oxygen ("non-isocapnic hyperventilation"-NIH).Material and methodsThe study involved 13 healthy, chronically-smoking volunteers. Each of them participated in two independent hyperventilation tests: IH and NIH. The levels of carboxyhemoglobin (COHb) and selected gasometric, cardiac and respiratory parameters were measured at 0, 10 and 20 minutes during both tests. Among 13 volunteers (8 women and 5 men) the initial COHb level was 5.0±1.5% (mean±SD) before the IH tests and 5.1±1.9% before the NIH tests (p>0.05). After 20 minutes of the procedures the mean COHb level was 2.9±0.9% for IH and 3.6±1.2% for NIH (p<0.01). The T½ of COHb was 29.6±12.2 min and 47.3±19.2 min respectively (p<0.01). After 10 minutes of NIH respiratory alkalosis was noted in 11 participants (84.6%). Such problem was not seen during the IH procedures. No serious adverse effects were recorded during either IH or NIH. Mild symptoms such as: dyspnea, headache and paresthesias were reported by 6 volunteers (46%) during both IH and NIH tests. It is worth noting that paresthesias were only reported during NIH, by 2 participants (15.4%).ConclusionsThe elimination T½ of CO during IH was comparable with the values reported during HOT, and lower than can be achieved with NOT or NIH. No serious adverse effects were reported during IH procedures. Further studies, especially direct comparisons with NOT and HOT, are necessary to evaluate the effectiveness of IH in the treatment of acute CO poisoning.

Project description:Presence of parkinsonian features after carbon monoxide (CO) intoxication is well known and the severity was found to relate to the pre-synaptic dopaminergic deficits. There is no systemic study to analyse the functional network involved in CO-related Parkinsonism. Forty-five CO-related parkinsonism patients and 25 aged-matched controls completed the 3D T1-weighted imaging and (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Voxel-based morphometry (VBM) was performed to assess the structural and functional brain differences between the patients and controls. Spatial covariant networks responsible for distinguishing patients and controls were constructed using independent component analysis. For validation, the pre-synaptic dopaminergic functional network was established by regression model using striatal TRODAT-1 SPECT as the independent variable. The clinical significance of both networks was determined by correlation with the Unified Parkinson's Disease Rating Scale (UPDRS). Compared with controls, the spatial covariant signals of FDG-PET were significantly lower in the medial and lateral frontal, caudate nucleus, dorsomedial prefrontal areas, and temporal-parietal regions while the spatial intensities correlated significantly with UPDRS total scores. The functional network that correlated with striatum pre-synaptic dopaminergic uptakes included the midbrain, thalamus, caudate, lateral frontal cortex, ventral striatum, ventral, or dorsal anterior cingulate cortex. Both networks overlapped considerably and the topographies reflected structural damage pattern. Our study provides evidence that glucose metabolism in CO-parkinsonism patients pertains to an organized covariant pattern in the cortical regions that is spatially coherent with the cortical map of pre-synaptic dopamine deficits. As the fronto-temporal, striatum, and temporal-parietal areas were involved, the unique metabolic covariant network suggests a different pathophysiology in CO-related parkinsonism.

Project description:BackgroundPomegranate fruit has been extensively used as a natural medicine in many cultures. The present study was aimed at evaluating the protective effects of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl4)-induced oxidative stress and testes injury in adult Wistar rats.MethodsTwenty eight Wistar albino male rats were divided equally into 4 groups for the assessment of protective potential of pomegranate juice. Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II and IV were treated with CCl4 (2 ml/kg bwt) via the intraperitoneal route once a week for ten weeks. The pomegranate juice was supplemented via drinking water 2 weeks before and concurrent with CCl4 treatment to group IV. Group III was supplemented with pomegranate juice for twelve weeks. The protective effects of pomegranate on serum sex hormones, oxidative markers, activities of antioxidant enzymes and histopathology of testes were determined in CCl4-induced reproductive toxicity in rats.ResultsPomegranate juice showed significant elevation in testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) those depleted by the injection of CCl4. Activity levels of endogenous testesticular antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and glutathione (GSH) contents were increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased with pomegranate juice. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were restored with the treatment of pomegranate juice.ConclusionThe results clearly demonstrated that pomegranate juice augments the antioxidant defense mechanism against carbon tetrachloride-induced reproductive toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.

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Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication.

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