Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

G-CSF Administration Attenuates Brain Injury in Rats Following Carbon Monoxide Poisoning via Different Mechanisms

(2017) G-CSF Administration Attenuates Brain Injury in Rats Following Carbon Monoxide Poisoning via Different Mechanisms. Environmental Toxicology. pp. 37-47. ISSN 1520-4081

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Abstract

Acute severe carbon monoxide (CO) poisoning induces hypoxia that leads to cardiovascular and nervous systems disturbances. Different complex mechanisms lead to CO neurotoxicity including lipid peroxidation, inflammatory and immune-mediated reactions, myelin degeneration and finally neuronal apoptosis and necrosis. Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel neuroprotective agent. In this study, we evaluated the efficacy of G-CSF therapy on CO neurotoxicity in rats with acute CO poisoning. Rats were exposed to 3000 ppm CO in air (0.3) for 1 h, and then different doses (50,100, and 150 mu g/kg) of G-CSF or normal saline were administrated intraperitoneally. Water content of brain as an indicator for total edema and blood brain barrier integrity (Evans blue extravasation) were evaluated. Malondialydehyde was determined in order to evaluate the effect of G-CSF on CO-induced lipid peroxidation in brain tissues. Also, the effect of G-CSF on myeloperoxidase activity in the brain tissue was evaluated. The effect of G-CSF administration on induced apoptosis in the brain was measured using TUNEL method. To evaluate the level of MBP, STAT3 and pSTAT3 and HO-1 proteins and the effect of G-CSF on these proteins Western blotting was carried out. G-CSF reduced water content of the edematous poisoned brains (100 mu g/kg) and BBB permeability (100 and 150 mu g/kg) (P<0.05). G-CSF (150 mu g/kg) reduced the MDA level in the brain tissues (P<0.05 as compared to CO poisoned animals). G-CSF did not decrease the MPO activity after CO poisoning in any doses. G-CSF significantly reduced the number of apoptotic neurons and Caspase 3 protein levels in the brain. Western blotting results showed that G-CSF treatment enhanced expression of HO-1 and MBP, STAT3 and pSTAT3 proteins in the brain tissues. Based on our results, a single dose of G-CSF immediately after CO poisoning significantly attenuates CO neurotoxicity via different mechanisms. (C) 2015 Wiley Periodicals, Inc.

Item Type: Article
Keywords: carbon monoxide poisoning granulocyte colony stimulating factor myelin basic protein neurotoxicity rat apoptosis malondialydehyde myeloperoxidase colony-stimulating factor focal cerebral-ischemia hyperbaric-oxygen hypoxia-ischemia heme oxygenase-1 cell-death mice expression apoptosis neuropathology Environmental Sciences & Ecology Toxicology Water Resources
Divisions:
Page Range: pp. 37-47
Journal or Publication Title: Environmental Toxicology
Journal Index: ISI
Volume: 32
Number: 1
Identification Number: https://doi.org/10.1002/tox.22210
ISSN: 1520-4081
Depositing User: مهندس مهدی شریفی
URI: http://eprints.bmsu.ac.ir/id/eprint/4611

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