Objective To explore effects of edaravone on apoptosis and expressions of apoptotic proteins Smac and XIAP in hippocampal CA1 pyramidal cell of rats under intermittent hypoxia. Methods A total of 96 adult male Wistar rats were randomly divided into control group, 5% intermittent hypoxic group and edaravone group, and each group was divided into 4 time groups at 7 d, 14 d, 21 d and 28 d, respectively, with 8 rats in each subgroup. The content of reactive oxygen species (ROS) in hippocampal tissues of the experimental rats was detected by the reactive oxygen species detection kit. Immunohistochemistry and Western blot were used to detect the expressions of Smac and XIAP protein in hippocampal CA1 region. The Tunel method detected the apoptosis of neurons. Results Compared with the control group, the content of ROS, the expressions of Smac and XIAP proteins and the neuronal apoptosis index in the hippocampus were increased in the 5% intermittent hypoxia group and the edaravone group at each time point (all P<0.05). The content of ROS, the Smac protein expression and the neuronal apoptosis index in the edaravone group were significantly lower than those in the 5% intermittent hypoxia group (all P<0.05). The expression of XIAP protein in the edaravone group was significantly higher than that in the 5% intermittent hypoxia group (P<0.05). Conclusion Edaravone may improve the antioxidant capacity of the body by scavenging oxygen free radicals and regulate Smac and XIAP- mediated apoptosis, thus playing a protective role on neurons.
Objective To evaluate the effectiveness and safety of edaravone combined with Xingnaojing injection in the treatment of adult acute cerebral infarction. Methods Databases including PubMed, EMbase, The Cochrane Library, CBM, CNKI, VIP and WanFang Data were searched from inception to March 2012 to identify the randomized controlled trials (RCTs) on edaravone combined with Xingnaojing injection for adult acute cerebral infarction. Two reviewers independently selected the literature, extracted the data and assessed the methodological quality of the included RCTs, and then meta-analysis was performed using RevMan 5.0 software. Results A total of 9 RCTs involving 1 098 patients were included. The results of meta-analyses showed: a) The edaravone combined with Xingnaojing injection group was superior to the Xingnaojing injection group with significant differences in the effective rate (OR=3.43, 95%CI 2.44 to 4.82, Plt;0.000 01), significantly-effective rate (OR=2.33, 95%CI 1.78 to 3.05, Plt;0.000 01), mortality (OR=0.38, 95%CI 0.15 to 0.95, P=0.04), ESS score after treatment (7 days after treatment: SMD=–0.48, 95%CI –0.80 to –0.17, P=0.003; 14 days after treatment: SMD=–0.89, 95%CI –1.17 to –0.62, Plt;0.000 01; 1 month after treatment: SMD=–0.89, 95%CI –1.20 to –0.59, Plt;0.000 01) and NDS score after treatment (7 days after treatment: MD=10.42, 95%CI 4.78 to 16.05, P=0.000 3; 14 days after treatment: MD=13.82, 95%CI 12.86 to 14.79, Plt;0.000 01; 21 days after treatment: MD=10.33, 95%CI 4.43 to 16.23, P=0.000 6); and b) The edaravone + Xingnaojing injection + conventional therapy group was superior to the conventional therapy group with significant differences in the effective rate (OR=3.03, 95%CI 1.36 to 6.73, P=0.006), significantly-effective rate (OR=2.86, 95%CI 1.50 to 5.44, P=0.001) and ESS score after treatment (7 days after treatment: MD=–6.26, 95%CI –8.49 to –4.03, Plt;0.000 01; 14 days after treatment: MD=–6.43, 95%CI –8.73 to –4.13, Plt;0.000 01). Conclusion Current evidence shows edaravone combined with Xingnaojing injection is obviously superior to either Xingnaojing injection or conventional therapy for adult acute cerebral infarction. But this conclusion still needs to be further proved by more high-quality and large-scale RCTs because of the low quality of the included studies.
Objective To observe the short-term effect and safety of hyperbaric oxygen combined with edaravone and ozagrel sodium in treating progressive cerebral infarction. Methods A total of 65 in-patients with acute progressive cerebral infarction were randomly divided into two groups: 33 in-patients in the trial group were treated by hyperbaric oxygen combined with edaravone and ozagrel sodium, while the other 32 in-patients in the control group were treated by edaravone and ozagrel sodium. The course of treatment was 14 days. The following indications were assessed before and after the treatment respectively: the national institutes of health stroke scale (NIHSS), activities of daily living (ADL), and clinical effects. Results This study showed that the scores of both ADL and NIHSS in the trial group were higher than those in the control group, with significant differences (Plt;0.05). The clinical effective rate of the trial group was 90.91% which was obviously higher than the control group with a significant difference (P=0.028). There were no obvious adverse reactions in both groups. Conclusion Hyperbaric oxygen combined with both edaravone and ozagrel sodium is notable in short-term effect and safe, thus it is worth being popularized in clinical treatment.
ObjectiveTo investigate the effects and clinical significance of edaravone on serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) in elderly patients with obstructive sleep apnea hypopnea syndrome (OSAHS).MethodsA total of 90 elderly patients with moderate to severe OSAHS confirmed by polysomnography were recruited from North China University of Science and Technology Affiliated Hospital in February 2016 to October 2017. According to random number table method the OSAHS patients were randomly divided into group A (n=30), group B (n=30) and group C (n=30). Group A received continuous positive airway pressure treatment for six months, group B received edaravone therapy and continuous positive airway pressure treatment for six months, and group C only received edaravone therapy for six months. The changes of serum TNF-α, IL-6 and ICAM-1 were detected by enzyme-linked immunosorbent assay before and after treatment.ResultsThe differences of serum TNF-α, IL-6 and ICAM-1 before treatment in the three groups were not statistically significant (P>0.05). Compared with before treatment, the levels of serum TNF-α, IL-6 and ICAM-1 decreased in the three groups (P<0.05). After six months of treatment, the levels of serum TNF-α, IL-6 and ICAM-1 decreased in group A and group B compared with group C (P<0.05), and decreased significantly in group B compared with group A (P<0.05).ConclusionEdaravone can inhibit the expressions of serum TNF-α, IL-6 and ICAM-1 in elderly patients with moderate to severe OSAHS, and thereby reduce vascular endothelial dysfunction and injury.
ObjectiveTo investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.MethodsA total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.ResultsHE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.ConclusionsThe expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.
Objective To investigate the impact of edaravone on serum reactive oxygen species during the perioperative period of off-pump coronary artery bypass grafting （OPCAB）. Methods A total of 40 patients who underwent selective OPCAB in the First Hospital of Hebei Medical University between June 2011 and November 2012 were prospectively enrolled in this study. All the patients were randomly divided into a trial group and a control group by a random digitaltable method with 20 patients in each group. There were 13 males and 7 females in the trial group with their age of 40-67（51.8±11.5） years， and 9 males and 11 females in the control group with their age of 42-70 （53.5±13.1） years. Afteranesthesia induction， patients in the trial group received continuous intravenous infusion of edaravone 60 mg （diluted in 100 ml saline）， while patients in the control group received continuous intravenous infusion of saline 100 ml， both of whichwere finished within 30 minutes. Venous blood samples were taken 24 hours preoperatively （T1）， 1 hour after skin incision（T2）， at the end of the surgery （T3） and 24 hours postoperatively （T4） to examine the concentration of superoxide dismutase（SOD） and malondialdehyde （MDA）. The data of the two groups were compared. Results All the patients successfully underwent their surgery and were included in the analysis. At the T2， T3 and T4 time point， SOD concentration was 80.3±21.3 U/ml， 78.5±17.4 U/ml and 81.4±17.5 U/ml， and MDA concentration was 10.2±1.8 nmol/ml， 11.3±1.9 nmol/ml，14.8±2.1 nmol/ml respectively in the control group；SOD concentration was 92.8±18.4 U/ml，90.0±18.1 U/ml，and 88.7±18.7 U/ml，and MDA concentration was 7.2±1.7 nmol/ml，8.2±1.2 nmol/ml，10.2±1.3 nmol/ml respectively in the trial group. At each above time point， SOD activity was significantly higher in the trial group than the control group （F=2.90，P=0.003；F=2.80，P=0.003；F=2.80，P=0.001）， and MDA concentration was significantly lower in the trial group than the control group （F=2.79，P=0.001；F=2.80，P=0.001；F=2.90，P=0.000）. Conclusion Edaravone can decrease serum reactive oxygen species caused by OPCAB and reduce myocardial injury.
Objective To observe the influence of edaravone perfusion via the pulmonary artery on postoperative lung tissue and lung function during pulmonary ischemia in deep hypothermic circulatory arrest （DHCA）， and explore its possible mechanism. Methods A total of 24 healthy New Zealand white big-ear rabbits were randomly divided into three groups： （1） control group： DHCA model under cardiopulmonary bypass （CPB） was established； （2）low potassium dextran （LPD）group： LPD solution perfusion via the pulmonary artery after the establishment of DHCA； （3）edaravone group：LPD solution containing edaravone （5 mg/kg） perfusion via the pulmonary artery after the establishment of DHCA. Oxygenation index and lung compliance were observed at the time of baseline condition， recovery of ventilation， 1 hour and 2 hours after recovery of ventilation， and postoperative lung function of the three groups were compared. Malondialdehyde （MDA） and superoxide dismutase （SOD） in pulmonary venous blood were measured. All the rabbits were sacrificed after the operation. HE staining and immunohistochemistry were performed on the lung tissues to investigate lung structure changes and inflammatory reaction. Transmission electron microscopy was used to compare ultrastructural changes of lung.Results There were no statistical difference in oxygenation index， lung compliance， MDA and SOD among the 3 groups under the baseline condition （P＞0.05）. After recovery of ventilation， oxygenation index and lung compliance deteriorated to varying degrees in all 3 groups. Oxygenation index and lung compliance of the control group and LPD group at the time of recovery of ventilation， 1 hour and 2 hours after recovery of ventilation were significantly lower than those of edaravone group （oxygenation index：recovery of ventilation and in control group and edaravone group: 198.25±11.02 mm Hg vs. 244.87±13.05 mm Hg；lung compliance：one hour after recovery ventilation in control group and edaravone group：45.88±1.64 ml/cm H2O vs. 59.75±2.38 ml/cm H2O；P＜0.05）. After CPB removal， MDA levels were increased to varying degrees in all 3 groups. MDA levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly higher than those of edaravone group （P＜0.05）. After CPB removal， SOD levels were decreased to varying degrees in all 3 groups. SOD levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly lower than those of edaravone group （P＜0.05）. HE staining showed clear lung structure， less red blood cell leakage， less inflammatory cell infiltration， and less alveolar fluid accumulation in the edaravone group. Immunohistochemistry showed that integral light density of interleukin 6 （IL-6）in edaravone group was significantly lower than those of the LPD group and control group （14.44±1.75 vs. 20.18±2.22， P＜0.05）. Transmission electron microscopy showed integral basement membrane structure， clear blood gas barrier structure， significantly larger number of type II epithelial cells， abundant but not swollen mitochondria and lamellar bodies in the cytoplasm in the edaravone group， which were destroyed in varying degrees in the LPD group and control group. Conclusion Pulmonary artery perfusion of protective solution in low temperature can significantly reduce lung injury induced by DHCA and CPB. Protective solution containing edaravone in low temperature can better decrease lung injury and protect oxygenation.
ObjectiveTo evaluate the effects and safety of edaravone combined with shuxuening for cerebral infarction. MethodsThe Cochrane Library, PubMed, EMbase, CBM, CNKI and VIP databases were searched from their establishments up to March 31, 2013. We used the method recommended by the Cochrane collaboration to perform a meta-analysis of randomized controlled trails (RCTs) with RevMan 5.0 software. ResultsSeventeen studies were included. The results of Meta-analysis demonstrated that edaravone combined with shuxuening were more efficient in reducing the score of neural function deficient scale and higher in the total effective rate (P<0.05), while there was no difference in the incidence of adverse reactions (P>0.05). ConclusionThe study suggests that edaravone combined with shuxuening is effective for cerebral infarction, but it also needs further studies to provide more sufficient evidence.
Objective To assess the effectiveness and safety of sodium ozagrel combined with edaravone for cerebral infarction. Methods Such databases as PubMed (1995 to 2010), EMCC (1995 to 2010), CBM (1995 to 2010), CNKI (1995 to 2010), and VIP (1989 to 2010) were searched to collect randomized controlled trials (RCTs) of odium ozagrel combined with edaravone for cerebral infarction. Then the retrieved studies were screened according to the predefined inclusion and exclusion criteria, the data were extracted, the quality of the included studies was evaluated, and meta-analyses were performed by using the Cochrane Collaboration’s RevMan 5.0 software. Results A total of 32 RCTs involving 3 059 cases were involved, among which 1 559 cases were in the treatment group and the other 1500 were in the control group. All studies with comparable baseline data reported the application of random methods without explaining the detailed methods, the blinding method and the allocation concealment. The results of meta-analyses indicated that sodium ozagrel combined with edaravone had significant differences in the effective rate for cerebral infarction compared with both single sodium ozagrel (OR=3.51, 95%CI 2.70 to 4.57) and routine treatment (OR=3.77, 95%CI 2.58 to 5.52), and it had significant differences in treating the defect of neurological function compared with both sodium ozagrel (WMD= –4.26, 95%CI –4.97 to –3.55) and routine treatment (WMD= –3.89, 95%CI –4.96 to –2.82). In addition, Sodium ozagrel combined with edaravone was superior to sodium ozagrel (WMD=13.57, 95%CI 9.84 to 17.30) in improving the ability of daily living. Conclusion This systematic review shows that sodium ozagrel combined with edaravone is quite effective in treating cerebral infarction, and it can improve the nerve dysfunction. This conclusion should be treated cautiously for the poor quality and higher possibility of bias in the included studies which may impact on the power of proof, so more double-blind RCTs with high quality are expected to provide high-quality evidence.
ObjectiveTo investigate the mechanism of the early kidney injury in rats caused by intermittent hypoxia, and investigate the intervention effect of edaravone.MethodsEighty male Wistar rats were randomly divided into a control group (NC), an intermittent hypoxia group (IH), an intermittent hypoxia edaravone treatment group (IH+NE), and an intermittent hypoxia normal saline matched group (IH+NS). After 4 weeks of model establishment, serum urea nitrogen and creatinine concentration were determined. Pathological changes of kidney were observed under light microscope, and ultrastructural changes of glomeruli and renal tubules were observed under electron microscope. The kidney injury molecule 1 (KIM-1) protein was detected by immunohistochemistry. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), hydroxyl radical and Bcl-2 mRNA, Caspase-3 mRNA, Bax mRNA in homogenate of kidney tissue were measured.ResultsSerum urea nitrogen in each group showed no significant difference. Serum creatinine increased significantly in IH group and significantly decreased after edaravone treatment. There were no significant pathological damages in NC group under light and electron microscopy. IH group showed varying degrees of renal tubule damages compared with NC group. Compared with NC group, the mean optical density of KIM-1 protein in IH group and IH + NS group significantly increased (P<0.01), and the mean optical density of KIM-1 protein in IH+NE group significantly decreased (P<0.01). Compared with NC group, the activity of SOD in IH group and IH+NS group significantly decreased, the content of MDA and hydroxyl radical increased, the expression of Bcl-2 mRNA decreased, the expression of Caspase-3 mRNA and Bax mRNA increased, Bcl-2/Bax decreased. After edaravone intervention, the activity of SOD in kidney tissue of rats significantly increased, the content of MDA and hydroxyl radical significantly decreased, the expression of Bcl-2 mRNA increased, the expression of Caspase-3 mRNA and Bax mRNA decreased, Bcl-2/Bax increased.ConclusionsIntermittent hypoxia can cause kidney injury through oxidative stress and regulation of Bcl-2, Bax and Caspase-3. KIM-1 may be used as a sensitive indicator for monitoring early kidney injury. Edaravone can prevent kidney injury induced by intermittent hypoxia though scavenging oxygen free radical, improving antioxidant capacity, regulating cell apoptosis mediated by regulating Bcl-2/Bax and Caspase-3.