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      Magnesium sulfate ameliorates carbon monoxide-induced cerebral injury in male rats

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          Abstract

          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 CO-induced 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 CO-exposed 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 dose-dependent manner in the MS-treated rats compared to the positive control group, while a significant dose-dependent increase in Akt expression, a pro-survival protein, was observed. In addition, MS administration reduced pro-apoptotic 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 CO-induced cerebral injury.

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          Most cited references57

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          Malondialdehyde determination as index of lipid peroxidation.

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            Apoptosis in neurodegenerative disorders.

            Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, stroke, and amyotrophic lateral sclerosis. The identification of specific genetic and environmental factors responsible for these diseases has bolstered evidence for a shared pathway of neuronal death--apoptosis--involving oxidative stress, perturbed calcium homeostasis, mitochondrial dysfunction and activation of cysteine proteases called caspases. These death cascades are counteracted by survival signals, which suppress oxyradicals and stabilize calcium homeostasis and mitochondrial function. With the identification of mechanisms that either promote or prevent neuronal apoptosis come new approaches for preventing and treating neurodegenerative disorders.
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              Hyperbaric oxygen for acute carbon monoxide poisoning.

              Patients with acute carbon monoxide poisoning commonly have cognitive sequelae. We conducted a double-blind, randomized trial to evaluate the effect of hyperbaric-oxygen treatment on such cognitive sequelae. We randomly assigned patients with symptomatic acute carbon monoxide poisoning in equal proportions to three chamber sessions within a 24-hour period, consisting of either three hyperbaric-oxygen treatments or one normobaric-oxygen treatment plus two sessions of exposure to normobaric room air. Oxygen treatments were administered from a high-flow reservoir through a face mask that prevented rebreathing or by endotracheal tube. Neuropsychological tests were administered immediately after chamber sessions 1 and 3, and 2 weeks, 6 weeks, 6 months, and 12 months after enrollment. The primary outcome was cognitive sequelae six weeks after carbon monoxide poisoning. The trial was stopped after the third of four scheduled interim analyses, at which point there were 76 patients in each group. Cognitive sequelae at six weeks were less frequent in the hyperbaric-oxygen group (19 of 76 [25.0 percent]) than in the normobaric-oxygen group (35 of 76 [46.1 percent], P=0.007), even after adjustment for cerebellar dysfunction and for stratification variables (adjusted odds ratio, 0.45 [95 percent confidence interval, 0.22 to 0.92]; P=0.03). The presence of cerebellar dysfunction before treatment was associated with the occurrence of cognitive sequelae (odds ratio, 5.71 [95 percent confidence interval, 1.69 to 19.31]; P=0.005) and was more frequent in the normobaric-oxygen group (15 percent vs. 4 percent, P=0.03). Cognitive sequelae were less frequent in the hyperbaric-oxygen group at 12 months, according to the intention-to-treat analysis (P=0.04). Three hyperbaric-oxygen treatments within a 24-hour period appeared to reduce the risk of cognitive sequelae 6 weeks and 12 months after acute carbon monoxide poisoning. Copyright 2002 Massachusetts Medical Society
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                February 2019
                17 December 2018
                17 December 2018
                : 19
                : 2
                : 1032-1039
                Affiliations
                [1 ]Department of Health, Zabol University of Medical Sciences, 9861615881 Zabol, Iran
                [2 ]Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences, 9177948564 Mashhad, Iran
                [3 ]Department of Cardiology, University Hospital of Larissa, 41110 Larissa, Greece
                [4 ]Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy, 200349 Craiova, Romania
                [5 ]Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, 9861615881 Zabol, Iran
                [6 ]Students Research Committee, School of Pharmacy, Zabol University of Medical Sciences, 9861615881 Zabol, Iran
                [7 ]Swiss Centre for Applied Human Toxicology, University of Basel, CH-4055 Basel, Switzerland
                [8 ]Department of Pathology, Amiralmomenin Hospital, Zabol University of Medical Sciences, 9861615881 Zabol, Iran
                [9 ]Department of Cardiology, Emam Reza Educational Center, Mashhad University of Medical Sciences, 9137913316 Mashhad, Iran
                [10 ]Department of Biostatisics and Epidemiology, Faculty of Public Health, Zabol University of Medical Sciences, 9861615881 Zabol, Iran
                [11 ]Laboratory of Clinical Virology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
                [12 ]Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
                Author notes
                Correspondence to: Professor Aristidis Tsatsakis, Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Voutes, 71003 Heraklion, Greece, E-mail: aris@ 123456med.uoc.gr ; tsatsaka@ 123456uoc.gr
                Professor Mahmoud Hashemzaei, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Shahid Rajaii Street, 9861615881 Zabol, Iran, E-mail: mhtoxicologist@ 123456gmail.com
                [*]

                Co-first authorship

                Article
                mmr-19-02-1032
                10.3892/mmr.2018.9771
                6323247
                30569139
                1e73efb1-739d-4c39-90b4-a16682e29a1a
                Copyright: © Bagheri et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 October 2018
                : 05 December 2018
                Categories
                Articles

                carbon monoxide poisoning,magnesium sulfate,cerebral ischemia,akt,necrosis,apoptosis,bax/bcl2 ratio,oxidative stress,malondialdehyde

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