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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.

Carbon monoxide (CO), which is produced by the incomplete combustion of hydrocarbons, has many toxic effects on different organs, especially the brain and heart. CO-induced cardiotoxicity leads to several deleterious effects, including electrocardiogram (ECG) abnormalities. The present study aimed to evaluate the protective effect of recombinant human granulocyte colony-stimulation factor (G-CSF) on ECG after CO poisoning in rats. Single and multiple doses of G-CSF (10, 50, and 100 µg/kg) were administered to groups, each containing 5 male Wistar rats (16 groups for ECG analysis and 16 groups for pathological analysis). Rats were already exposed to CO at either 1,500 or 3,000 ppm concentrations for 60 minutes. ECG findings (e.g., ST-segment and T-wave changes), cardiac arrhythmias (e.g., heart blocks and ventricular and supraventricular arrhythmias), and histological changes were determined after G-CSF administration. At 3,000 ppm, frequencies of ST elevation, depression, and T inversion in ECG were significantly reduced after G-CSF treatment. Also, some of the cardiac arrhythmias (e.g., atrioventricular block type 1 and 2) after CO poisoning were suppressed after G-CSF treatment. However, G-CSF did not show protective effects on cardiomyocyte pathological consequences in CO-poisoned rats. Therefore, G-CSF could protect against ECG changes after CO-induced cardiac ischemia, but did not affect pathological changes.

Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel neuroprotective agent. Beneficial effects have been demonstrated by administrating G-CSF in different experimental stroke models. In this study, we evaluated the efficacy of G-CSF therapy on carbon monoxide (CO) neurotoxicity in rats exposed to acute CO poisoning. Immediately after exposure to 3,000 ppm of CO for 60 minutes, 50, 100, and 150 µg/kg of G-CSF or normal saline were administered to rats. Rats were sacrificed after 24 hours for serum marker analysis or 1 week for histopathological examination. Brain sections were stained with hematoxylin and eosin to assess leukocyte infiltration and hippocampal injury and with Luxol fast blue to assess demyelination. S100β and glial fibrillary acidic protein (GFAP) serum levels were evaluated by commercial enzyme-linked immunosorbent assay kits. According to histopathological findings, G-CSF administration significantly restricted white-matter demyelination (150 µg/kg) (P = 0.006). Also, serum levels of S100β in G-CSF-treated groups (100 and 150 µg/kg) decreased significantly (P < 0.01 and P < 0.05, respectively). In all does, G-CSF significantly reduced serum levels of GFAP (P < 0.01 for 50 µg/kg and P < 0.001 for other doses). Administration of G-CSF after CO poisoning attenuates brain cell damage through remyelination. G-CSF also decreases levels of related biomarkers, such as S100β and GFAP.

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