A pilot study of neuroprotective effect of granulocyte colony-stimulating factor (G-CSF) in patients with carbon monoxide poisoning: a double-blind, randomized, placebo-controlled trial.

Although neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) have been shown in rats exposed to carbon monoxide (CO), this pilot clinical trial was performed to assess the feasibility of treatment with G-CSF in patients with acute CO poisoning. A double-blind, randomized, placebo-controlled pilot clinical trial was conducted on twenty-six patients with acute CO poisoning. G-CSF (90 µg/kg) was administered intravenously for 72 h. Demographic data, routine laboratory tests, differential blood counts, venous blood gas, and adverse reactions were recorded. The primary endpoint was brain ischemia improvement based on CT findings and the secondary endpoints examined improvements in the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index as well as S-100ß concentrations. Fourteen patients received G-CSF, and 12 received a placebo. Twenty-six were followed for 30 days and no one in both groups died during follow-up. Neurological complications, brain ischemic changes, Barthel, and mRS were compared between the two groups on determined days after the onset of therapeutic intervention, and no significant differences were observed between the two groups. Favorable results were achieved for treated patients by different measures; NIHSS was decreased 72 h after treatment (p = 0.046), and S-100ß levels were significantly higher in the G-CSF group than in the control group, 12 h and 72 h after the treatment. G-CSF appears to have potential effects on several clinical parameters in patients with acute CO poisoning. The trial was registered at the Iranian Registry of Clinical Trials with the ID: (IRCT201607232083N7).

Evaluation of the Cardioprotective Effect of Granulocyte Colony Stimulating Factor in Patients with Carbon Monoxide Poisoning.

BACKGROUND: Carbon monoxide (CO), which is well known as silent killer, has many toxic effects on organs with high rate of metabolism such as heart and brain. CO-induced cardiotoxicity resulted in a wide range of disabilities including electrocardiogram (ECG) abnormalities, elevation in level of cardiac enzymes, arrhythmias, impairment of left ventricular and myocardial infarction (MI). Cardio-protective effects of Granulocyte colony-stimulating factor (G-CSF) on infarcted heart was proved previously in various reports. OBJECTIVE: In this study, possible effect of G-CSF on cardiac function of patients with moderate to severe acute CO poisoning was investigated. METHODS: Cardioprotective effects of G-CSF in CO-poisoned patients was evaluated through ECG, Holter monitoring, echocardiography, and biochemical studies. Continuous intravenous infusion of G-CSF (90 µg/kg) and normal saline were administered respectively to treatment and placebo groups. RESULTS: The results demonstrated that in moderate to severe CO poisoning, myocardial injury is common. ECG changes (e.g., ST-segment and T-wave changes, QTC), cardiac arrhythmias (e.g., heart blocks and ventricular arrhythmias), serum level of Troponin I, left ventricular ejection fraction were determined after G-CSF administration. Frequencies of ST depression, inversion or flatting of T wave and QTC in ECG were significantly reduced after G-CSF treatment. In addition, incidence of cardiac arrhythmias due to CO poisoning were reduced after G-CSF treatment. However, G-CSF did not exert protective effects on TPI level and function of left ventricular in CO-poisoned patients. CONCLUSION: GCSF could probably reduce CO-induced cardiac ischemia in patients with acute CO poisoning. CLINICAL TRIAL REGISTRATION: The trial protocol was registered in the Iranian Registry of Clinical Trials (http://www.irct.ir) registry (Irct ID: IRCT201607232083N7).

Application of Erythropoietin in Chronic Heart Failure Treatment.

Heart Failure (HF) is recognized as an important public health concern worldwide, especially in developed countries, due to its high rate of morbidity and mortality. Although new pharmacological and non-pharmacological agents have improved the clinical sequelae of HF in patients, its mortality remains high, especially among the elderly. Erythropoietin (EPO), a glycoprotein, besides its traditional role in promoting erythropoiesis and production of erythroid progenitors, its beneficial role in reducing infarct area and improving heart function through EPO-induced antiapoptotic and antioxidant effects have been increasingly recognized. This review gathers the evidence to date about the effectiveness of EPO in HF patients. In addition to the growing evidence of EPO in the treatment of HF in the animal studies for improving cardiac function and infarct size, more clinical studies are needed to assess the role of EPO treatment in the management of HF.

Application of G-CSF in Congestive Heart Failure Treatment.

INTRODUCTION: Congestive Heart Failure (CHF) is a disorder in which the heart is unable to supply enough blood for body tissues. Since heart is an adaptable organ, it overcomes this condition by going under remodeling process. Considering cardiac myocytes are capable of proliferation after MI, stimulation of neovascularization as well as their regeneration might serve as a novel target in cardiac remodeling prevention and CHF treatment. Granulocyte Colony-Stimulating Factor (G-CSF), is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophils and is involved in cardiac repair after MI. So far, this is the first review to focus on GCSF as a novel treatment for heart failure. METHODS: We conducted a search of some databases such as PubMed for articles and reviews published between 2003 and 2017, with different keywords including "G-CSF", "congestive heart failure", "new therapies for CHF", "filgrastim", "in vivo study". RESULTS: GCSF exerts its beneficial effects on cardiac repair through either stem cell mobilization or direct angiogenesis promotion. All of which are capable of promoting cardiac cell repair. CONCLUSION: GCSF is a promising target in CHF-therapy by means of cardiac repair and remodeling prevention through multiple mechanisms, which are effective enough to be used in clinical practice.

Recognition and characterization of Erythropoietin binding-proteins in the brain of mice.

OBJECTIVES: Erythropoietin (EPO), is a 34KDa glycoprotein hormone, which belongs to type 1 cytokine superfamily. EPO involves in erythrocyte maturation through inhibition of apoptosis in erythroid cells. Besides its main function, protective effects of EPO in heart and brain tissues have been reported. EPO has a critical role in development, growth, and homeostasis of brain. Furthermore EPO has great potential in the recovery of different brain diseases which are still under studying. In this research, EPO binding pattern to brain proteins in animal model was studied. MATERIALS AND METHODS: EPO antibody was covalently crosslinked to protein A/G agarose. in order to interact between EPO and its target in brain, about 5µg EPO added to brain homogenates(500ul of 1 mg/ml) and incubate at 4ο C for 30 min. brain tissue lysate were added to agarose beads, After isolation of target proteins(EPO - protein) both one and two-dimensional gel electrophoresis were performed. Proteins were identified utilizing MALDI-TOF/TOF and MASCOT software. RESULTS: This research showed that EPO could physically interact with eightproteins including Tubulin beta, Actin cytoplasmic 2, T-complex protein 1, TPR and ankyrin repeat-containing protein 1, Centromere-associated protein E, Kinesin-like protein KIF7, Growth arrest-specific protein 2 and Pleckstrin homology-like domain family B member 2. CONCLUSION: Since EPO is a promising therapeutic drug for the treatment of neurological diseases, identified proteins may help us to have a better understanding about the mechanism of protective effects of EPO in the brain. Our data needs to be validated by complementary bioassays.

Screening and identification of SUMP-proteins in sub-acute treatment with diazinon.

OBJECTIVES: Small ubiquitin-like modifiers (SUMOs) are a family of ubiquitin-related, proteins that are involved in a wide variety of signaling pathways. SUMOylation, as a vital post translational modification, regulate protein function in manycellular processes. Diazinon (DZN), an organophosphate insecticide, causses oxidative stress and subsequently programmed cell death in different tissues. The aim of this study was to evaluate the role and pattern of SUMO modificationas a defense mechanism against stress oxidative, in the heart tissuesof the DZN treated rats. MATERIALS AND METHODS: Diazinon (15 mg/kg/day), corn oil (control) were administered via gavageto male Wistar rats for four weeks. SUMO1 antibody was covalently crosslinked to protein A/G agarose. heart tissue lysate were added to agarosebeads, After isolation of target proteins(SUMO1- protein)SDS-PAGE gel electrophoresis was performed. Protein bands were identified using MALDI-TOF/TOF and MASCOT). Fold change of (DZN/Ctrl) separated proteins was evaluated using UVband software (UVITEC, UK). RESULTS: Our result showed that subacute exposure to DZN increased SUMOylationoffour key proteins involved in the metabolic process including; Acyl-CoA dehydrogenase, creatine kinase, glyceraldehyde-3-phosphate dehydrogenase and ATP synthase, in the heart tissue of animals. A probability value of less than 0.05 was considered significant (P<0.05). CONCLUSION: It seems that protein SUMOylation provides a safeguard mechanism against DZN Toxicity.