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.
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.
Objective To explore the potential protective effect in vivo of Edaravone, a free radical scavenger on model of acute lung injury in rats with sepsis. Methods Twenty-four male Wistar rats were randomly divided into three groups, ie. a control group( NS group) , a model group( LPS group) , a Edaravone treatment group( ED group) . ALI was induced by injecting LPS intravenously( 10 mg/ kg) in the LPS group and the ED group. Meanwhile the ED group was intravenously injected with Edaravone( 3 mg/ kg) . The NS group was injected with normal saline as control. The lung tissue samples were collected at 6 h after intravenous injection. The wet / dry ( W/D) weight ratio of lung tissue was measured. The levels of myeloperoxidase ( MPO) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD) in lung tissue homogenate were assayed. The pathological changes and expression of nuclear factor-kappa B( NF-κB) in lung tissue were also studied. Results Compared with the NS group, The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the LPS group were significantly higher( all P lt; 0. 01) , and the level of SOD was apparently lower( P lt; 0. 01) . The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the ED group were significantly lower than those in the LPS group( all P lt; 0. 01) and higher than those in the NS group( all P lt; 0. 01) . And the level of SOD in lung tissue of the ED group was higher than that in the LPS group and lower than that in the NS group ( P lt; 0. 01) . Conclusions Edaravone has protective effect on ALI rat model. The mechanismmay be related to its ability of clearing the reactive oxygen species, inhibiting the activation of the signal pathway of NF-κB and inflammatory cascade.
Objective To study the effects of edaravone on the lung injury of severe acute pancreatitis （SAP） in rats. Methods Thirty-six SD rats were randomly divided into three groups: normal control group, model group and edaravone group, and SAP was induced by intraductal administration of 5% sodium taurocholate. Edaravone was given in edaravone group, while normal saline was given in normal control group and model group. After operation 6 h rats were executed, and dry/wet weight (D/W) ratio of lung was counted, and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity in serum and lung were detected, respectively. In addition, the levels of tumor necrosis factor-α (TNF-α), interleukin-1, -6 (IL-1, -6) of serum were detected.Results The MDA contentof serum and lung and the levels of TNF-α, IL-1, IL-6 in model group were markedly higher than those in normal control group and edaravone group, but D/W ratio of lung, SOD activity of serum and lung were significantly lower (Plt;0.05). Conclusion Edaravone can alleviate lung injury of rats caused by SAP.
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.
Objective To assess the effectiveness and safety of edaravone for acute cerebral infarction. Methods We searched The Cochrane Central Register of Controlled Trials （ Issue 2, 2005 ）, MEDLINE （ 1966 to Aug. 2005）, EMBASE （ till Aug. 2005 ）, the China Biological Medcine Database （ till Aug. 2005 ）, the Chinese Stroke Clinical Trials Database （ till August 2005 ） and the reference lists of related articles. Two reviewers independently selected studies, assessed quahty of studies and extracted data. The RevMan 4.2 software was used for statistical analysis. Results We identified 12 randomized controlled trials, of which 9 （ n = 948 ） were included. The level of methodology quality was B. Since the conventional therapy was different among some studies, the improvement of disability and long-term death rate and incidence of adverse reactions were not included by meta-analysis. Meta-analysis on the improvement of neurological deficit showed a better effectiveness of edaravone than control with statistical significance [ OR2.98, 95% CI （ 1.39,6.39 ） ]. Possible adverse reactions to edaravone included abnormal liver function and skin rash. Conclusions With relatively poor quality of most included trials and small sample size, insufficient evidence is obtained to support the conclusion that edaravone is safe or effective in the treatment of acute cerebral infarction. Further high quality and large sample randomized controlled trials should be carried out.
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 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.
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.