G‐CSF administration attenuates brain injury in rats following carbon monoxide poisoning via different mechanisms

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 µg/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 µg/kg) and BBB permeability (100 and 150 µg/kg) (P < 0.05). G-CSF (150 µg/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. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 37-47, 2017.

Neuro‐Protective Effects of Resveratrol on Carbon Monoxide‐Induced Toxicity in Male Rats

“…Our previous study showed that RES could ameliorate CO‐induced cardiovascular effects in an animal model (Hashemzaei et al , ). In order to find new substances that can fight the deleterious effects of CO poisoning in the heart and brain and also to shed light on the underlying mechanisms, in our previous studies, we discussed the involved pathways (Ghorbani et al , ; Hashemzaei et al , ; Mohamadpour et al , ). To the best of our knowledge, it is for the first time that the neuroprotective effect of multiple‐dose RES administration on CO poisoning is evaluated in rats.…”

Involvement of p38 mitogen‐activated protein kinase in altered expressions of AQP1 and AQP4 after carbon monoxide poisoning in rat astrocytes

“…CO poisoning is one of the most common clinical emergencies, and effective disease models are critical to the study of underlying mechanisms and developing novel therapeutic strategies. Numerous studies have adopted suction canisters to induce CO intoxication model . However, since the variability of animal activity resulted in various breathing rate, the exposure of CO among animals lacked comparability.…”

“…Numerous studies have adopted suction canisters to induce CO intoxication model. 41,42 However, since the variability of animal activity resulted in various breathing rate, the exposure of CO among animals lacked comparability. In this study, inspired by Fecther 43,44 who induced cochlea injury by means of CO injection ip, we used CO ip injection to establish acute CO poisoning model.…”

Neurologic and Pregnancy Effects of Carbon Monoxide Exposure

“…In addition, CO exposure has been shown to cause lipid peroxygenation, (i.e. degradation of unsaturated fatty acids) leading to reversible demyelination of CNS lipids [22]. CO exposure also creates substantial oxidative stress on cells, with production of oxygen radicals resulting from the conversion of xanthine dehydrogenase to xanthine oxidase [23].…”