Edaravone Pretreatment Research Articles

Effects of edaravone on testicular torsion-detorsion injury in rats.

This study aimed to assess the protective ability of edaravone on testicular torsion-detorsion injury in rats. Eighteen adult male Sprague-Dawley rats were randomly divided into three groups: Sham group (control, n=6); testicular torsion/detorsion (T/D group, n=6) and T/D+edaravone (T/D+E group, n=6). The spermatic cords of rats of the T/D group and the T/D+E group were rotated 720° in a clockwise direction and maintained for 120min in this torsion position. Around 90min after the torsion, edaravone at a dose of 10mg/kg dissolved in saline was administered IP to the T/D+E group. The testicle was counter-rotated to its normal position to allow reperfusion for 4h. Left testes of each animal were excised 240min after beginning of reperfusion. Oxidative stress markers (TAS, TOS, SOD, and MDA) and apoptotic pathways (Caspase 3, Caspase 8, Caspase 9, Bcl-2, and Bax,) were assessed by ELISA methods. Also, testicles were subjected to the histopathologic and ultrasound examinations. Ultrasound imaging showed that edaravone reduced the surface area and increased vascularization in testicles with T/D (p<0.0001, p<0.05, respectively). Edaravone pretreatment markedly decreased the levels of MDA, TOS, Bcl-2, Bax, Caspase 3, Caspase 8, and Caspase 9 (p<0.0001). Also, it increased significantly TAS levels (p<0.0001) and reduced insignificantly SOD activity. Histopathologic examinations demonstrated that edaravone significantly attenuated the histological damage caused by T/D in testicles. Taken together, the findings indicate that pretreatment of edaravone has protective effect against testicular T/D injury.

Anticonvulsive effects of edaravone on penicillin-induced focal onset seizure model in the conscious rats.

Edaravone is a potent antioxidant and anti-inflammatory agent that is used in the clinic. The aim of the present study was to evaluate the chronic treatment effect of edaravone on penicillin-induced epileptiform activity. Twenty-eight Wistar rats were randomly divided into a total of four groups as penicillin control and edaravone pretreatment groups (1, 10, and 30mg/kg). Firstly, permanent electrodes for electrocorticography (ECoG) recording and canula for penicillin injection were placed as stereotactic under anesthesia. At the end of the recovery period, edaravone pretreatment groups received different doses of edaravone by intraperitoneal injection for 14 days and before 30-min penicillin microinjection. Epileptiform activity was induced by injecting 500 IU penicillin through the intracortical cannula. The effects of edaravone pretreatment on epileptiform activity were evaluated by using both electrophysiological and behavioral parameters. Edaravone pretreatment suppressed epileptiform activity by reducing the mean spike frequency and the behavior scores in ECoG recording. The results of the present study indicated that the use of chronic edaravone had an anticonvulsant effect on penicillin-induced focal onset epileptic activity. Edaravone had an anticonvulsant effect even at low doses.

Edaravone Alleviated Propofol-Induced Neurotoxicity in Developing Hippocampus by mBDNF/TrkB/PI3K Pathway.

BackgroundTo investigate the neuroprotective effect of edaravone on excessive-dose propofol-induced neurotoxicity in the hippocampus of newborn rats and HT22 cells.MethodsCell proliferation was investigated by assessing ki67 expression in the neural stem of the hippocampus of newborn rats and by cell counting kit-8 (CCK8) assay in HT22 cells. Cell apoptosis was assessed in vivo by caspase 3 detection in Western blots and measurement of apoptosis in neurons and glial cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Apoptosis was analyzed by flow cytometry in HT22 cells. The Morris water maze was used to evaluate the long-term learning and memory ability of rats. Inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The expression of mBDNF/TrkB/PI3K pathway-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction (q-RT PCR).ResultsIn neonatal rat hippocampus and HT22 cells, edaravone increased cell proliferation and decreased cell apoptosis after excessive propofol-induced neurotoxicity. In addition, the levels of proinflammatory factors interleukin (IL)-6 and tumor necrosis factor (TNF)-α were reduced by edaravone pretreatment. The use of the tropomyosin receptor kinase B (TrkB) antagonist ANA-12 and TrkB agonist 7,8DHF with propofol groups showed that edaravone mitigated excessive propofol-induced neurotoxicity through the mature brain-derived neurotrophic factor (mBDNF)/TrkB/phosphoinositide 3-kinase (PI3K) pathway. However, the current dose of propofol did not significantly affect long-term learning and memory in rats.ConclusionEdaravone pretreatment ameliorated propofol-induced proliferation inhibition, neuroapoptosis, and neural inflammation by activating the mBDNF/TrkB/PI3K pathway.

Edaravone Improves the Post-traumatic Brain Injury Dysfunction in Learning and Memory by Modulating Nrf2/ARE Signal Pathway

OBJECTIVES:To investigate the molecular mechanism of edaravone (EDA) in improving the post-traumatic brain injury (TBI) dysfunction in learning and memory.METHODS:In vitro and in vivo TBI models were established using hydrogen peroxide (H2O2) treatment for hippocampal nerve stem cells (NSCs) and surgery for rats, followed by EDA treatment. WST 1 measurement, methylthiazol tetrazolium assay, and flow cytometry were performed to determine the activity, proliferation, and apoptosis of NSCs, and malondialdehyde (MDA), lactic dehydrogenase (LDH), and reactive oxygen species (ROS) detection kits were used to analyze the oxides in NSCs.RESULTS:Following EDA pretreatment, NSCs presented with promising resistance to H2O2-induced oxidative stress, whereas NSCs manifested significant increases in activity and proliferation and a decrease in apoptosis. Meanwhile, for NSCs, EDA pretreatment reduced the levels of MDA, LDH, and ROS, with a significant upregulation of Nrf2/antioxidant response element (ARE) signaling pathway, whereas for EDA-treated TBI rats, a significant reduction was observed in the trauma area and injury to the hippocampus, with improvement in memory and learning performance and upregulation of Nrf2/ARE signaling pathway.CONCLUSIONS:EDA, by regulating the activity of Nrf2/ARE signal pathway, can improve the TBI-induced injury to NSCs and learning and memory dysfunction in rats.

Effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery: A randomized controlled trial.

Postoperative cognitive dysfunction (POCD) is a complication of central nervous system in patients after surgery. Edaravone as a brain-protective agent may have protective effect on postoperative cognitive function. The study was designed to explore the effects of edaravone on postoperative cognitive function in elderly patients undergoing hip joint replacement surgery and potential mechanism. Patients undergoing hip joint replacement surgery were randomly allocated into 2 groups: the edaravone group (group E) and the control group (group C). Group E received intravenous edaravone at a dose of 0.5mg/kg after induction of anesthesia, while group C received normal saline. The cognitive function was evaluated with the Mini-Mental State Examination (MMSE) 1day before surgery,3 days and the 7 days after surgery. Patients' plasma samples were collected to detect the levels of S100β protein (S100β), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), superoxide dismutase (SOD) and malondialdehyde (MDA) before the induction of anesthesia, at the end of surgery and on postoperative day 3. The MMSE scores in group E were higher than those of group C 3 days after surgery (25.98±1.99 vs 24.86±1.86, p=0.003). There were remarkable rises (p<0.05) in plasma IL-6, S100βand MMP-9 levels at the end of surgery and on postoperative day 3 in the two groups, however, edaravone pretreatment could reduce these levels to a certain extent compared with group C (p<0.05).In group E, the SOD concentration was higher at the end of surgery (16.03±2.46U/ml vs. 13.65±2.53U/ml, p=0.0001), while the MDA level was lower on postoperative day 3 than those in group C (7.01±2.37nmol/ml vs. 11.34±3.18nmol/ml, p=0.0001). The results indicated that preoperative intervention with edaravone may improve the postoperative cognitive function in elderly patients undergoing hip joint replacement surgery.

Edaravone inhibits autophagy after neuronal oxygen-glucose deprivation/recovery injury

Purpose of the study: Edaravone is an oxygen free radical scavenger that is widely used to treat ischemic injury to the nervous system. This study investigated the effect of edaravone pretreatment on neurons subjected to oxygen-glucose deprivation/recovery (OGD/R) injury.Materials and methods: Common neurons were subjected to oxygen and glucose deprivation for 1 h, followed by oxygen and glucose recovery for 0.5, 2, 6 and 12 h to establish the OGD/R model. Autophagy was assessed by electron microscope observation of autophagosomes, cell immunofluorescence, mRFP-GFP-LC3 virus cell fluorescence and western blotting analyses of the autophagy-related proteins. The findings showed that at OGD/R 2 h autophagy was high. Next, neurons were pretreated with different concentrations of edaravone (0, 5, 10, 25, 50 and 100 μM) before establishing the OGD/R model. Western blotting was used to analyze the expression of autophagy-related proteins. The CCK-8 assay was used to analyze cell viability after pretreatment with different concentrations of edaravone. Optimal inhibition of autophagy was achieved with the concentration of edaravone 50 μM. Neurons pretreated with 50 μM edaravone and established OGD/R model were analyzed for autophagy levels. Results: At every OGD/R time point autophagy was lower in neurons pretreated with edaravone than in those not pretreated with the drug. The difference was statistically significant without OGD/R 12 h. Conclusions: Pretreatment with edaravone may reduce the level of autophagy in neurons subjected to OGD/R injury.

Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway.

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury

Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI.

Protective Effect of Edaravone Against Aβ25-35-Induced Mitochondrial Oxidative Damage in SH-SY5Y Cells.

Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated. SH-SY5Y cells exposed to Aβ25-35 had high levels of apoptosis and ROS; loss of ΔΨm, decreased ATP levels and presence of mitochondrial swelling. However, these effects were significantly inhibited by edaravone pre-treatment. These results indicate that edaravone prevents mitochondria oxidative damage caused by Aβ in SH-SY5Y cells, which suggests that it may have potential clinical application in AD therapy.

Pretreatment with the Free Radical Scavenger Edaravone Mitigates Kidney Glycogen Depletion and Neutrophil Infiltration after Leg Ischemia in a Rat Model: A Pilot Study.

Objective: We have previously shown that pretreatment with the free radical scavenger edaravone (Radicut®, Mitsubishi Tanabe Pharma Co., Japan) mitigated skeletal muscle damage due to ischemia reperfusion. In this study, we sought to validate its use in an experimental model of myonephropathic-metabolic syndrome (MNMS).Methods: Either edaravone (3.0 mg/kg; edaravone group; n=4) or saline (saline group; n=6) was intraperitoneally injected into male Lewis rats (508±31 g). Normal kidneys were harvested as control (n=3). MNMS was induced by bilaterally clamping the common femoral arteries for 5 h and declamping 5 h later. Kidney damage was evaluated by quantifying Periodic Acid Schiff (PAS)-positive area (glycogen storage) and esterase-positive cells (neutrophil infiltration).Results: The PAS-positive area in the saline group was significantly lower than that in the normal group (36.9±2.6 vs. 66.9±1.2%, P<0.01); the PAS-positive area in the edaravone group remained comparable to that in the normal group (52.9±0.9%, P<0.01). Esterase-positive cells in the saline group were significantly higher than in normal kidneys (62.4±5.6 vs. 17.5±2.4 cells/mm2, P<0.01), while they were significantly reduced in the edaravone group (32.8±5.7 cells/mm2, P<0.01).Conclusion: Edaravone pretreatment mitigates MNMS-induced kidney damage by reducing both glycogen depletion and neutrophil infiltration.

Edaravone protects against cobalt chloride-induced dysfunctions in apoptosis and invasion in trophoblast cells.

This study was performed to investigate the effects of edaravone on hypoxia-induced trophoblast cell proliferation, apoptosis, and invasion. The trophoblast cell line HTR-8 (H8) was treated with cobalt chloride (CoCl2 ) with or without a 1-hr edaravone pretreatment, followed by assessment of intracellular reactive oxygen species (ROS) levels, cell proliferation, apoptosis, migration, and invasion. Metrics of apoptosis included measurement of cysteine-aspartic acid protease 3 (CASP3) activity as well as BAX and BCL2 expression. Migration and invasion phenotypes were complemented with expression analysis of matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2) at the transcript and protein levels. CoCl2 inhibited the proliferation of H8 cells, promoted apoptosis, and up-regulated CASP3 activation and BAX expression while inhibiting BCL2 expression. CoCl2 treatment also reduced the invasiveness of H8 cells by inhibiting MMP2 activity. Edaravone significantly increased H8 cell proliferation; inhibited apoptosis by down-regulating CASP3 activation and BAX production while promoting BCL2 stability; and ameliorated the migration and invasion phenotypes associated with CoCl2 treatment. These results suggest that edaravone may rescue hypoxia-induced abnormalities in H8 cell proliferation, apoptosis, and invasion, thereby protecting the trophoblast lineage against hypoxia. Mol. Reprod. Dev. 83: 576-587, 2016. © 2016 Wiley Periodicals, Inc.

Edaravone promotes activation of resident cardiac stem cells by transplanted mesenchymal stem cells in a rat myocardial infarction model

ObjectiveTo explore the effect of edaravone on bone marrow mesenchymal stem cells (BMSCs) transplanted to treat acute myocardial infarction (AMI) and the underlying mechanism. MethodsAfter pretreatment or treatment with edaravone under conditions of deep hypoxia and serum deprivation, the rat BMSCs were evaluated for reactive oxygen species (ROS), Akt pathway, apoptosis, migration, and paracrine function mediating cardiac stem cell (CSC) activation. Edaravone-pretreated BMSCs, control-released edaravone, and BMSCs were respectively transplanted into a rat AMI model. Apoptosis and paracrine functions of the BMSCs, resident CSC activation, and myocardial regeneration and function were measured at various time points. ResultsCompared with the control and edaravone pretreatment, edaravone treatment showed significantly increased apoptosis inhibition, migration, and cytokine secretion of BMSCs under an in vitro deep hypoxia and serum deprivation condition (P < .05), via inhibiting intracellular accumulation of ROS and prolonging the Akt pathway activation. At 24 hours postoperatively, up-regulated expression of cytokines within the transplanted area, and decreased apoptotic BMSCs, were detected in the BMSC + edaravone group, compared with the BMSCs and edaravone pretreatment BMSC groups (n = 10 for each group, P < .05). Four weeks later, the BMSCs + edaravone group showed more CSCs, CSC-derived cardiomyocytes, new vessels, and myocardial density within the ischemic area, and improved ejection fraction, compared with the other groups (n = 10 in each group, P < .05). ConclusionsEdaravone can protect the BMSCs against hypoxia and activate their potential to activate CSCs via the Akt pathway. The combined treatment can promote angiogenesis, resident CSC-mediated myocardial regeneration, and cardiac function after AMI, providing a new strategy for cell therapy.

Protective Effects of Edaravone against Methamphetamine-Induced cardiotoxicity

Methamphetamine (METH) is widely abused in worldwide. METH use could damage the dopaminergic system and induce cardiotoxicity via oxidative stress and mitochondrial dysfunction. Edaravone, a sedative-hypnotic agent, is known for it's antioxidant properties. In this study we used edaravone for attenuating of METH-induced cardiotoxicity in rats. The groups (six rats in each group) were as follows: control, METH (5 mg/kg IP) and edaravone (5, 10 and 20 mg/kg, IP) was administered 30 min before METH. After 24 hours, animals were killed, heart tissue was separated and mitochondrial fraction was isolated and oxidative stress markers were measured. Edaravone significantly (p<0.05) protected the heart against lipid peroxidation by inhibition of reactive oxygen species (ROS) formation. Edaravone also significantly (p<0.05) increased the levels of heart glutathione (GSH). METH administration significantly (p<0.05) disrupted mitochondrial function that edaravone pre-treatment significantly (p<0.05) inhibited METH-induced mitochondrial dysfunction. Protein carbonyl level also increased after METH exposure, but was significantly (p<0.05) decreased with edaravone pre-treatment. These results suggested that edaravone is able to inhibition of METH-induced oxidative stress and mitochondrial dysfunction and subsequently METH-induced cardiotoxicity. Therefore, the effectiveness of this antioxidant should be evaluated for the treatment of METH toxicity and cardio degenerative disease.

Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10mg/kgi.p.) once daily for 14days. On the 14th day 30min after edaravone treatment mice were challenged with LPS (1mg/kgi.p.). After 3h and 24h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12h of LPS administration. Moreover, after 24h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10mg/kg).Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage.

Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p < 0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb

BackgroundStudies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and damage to skeletal muscle. The purposes of this study were 1) to assess the histological findings of gastrocnemius muscle (GC) and tibialis anterior muscle (TA) in I/R injury model mice, 2) to histologically analyze whether a single pretreatment of edaravone inhibits I/R injury to skeletal muscle in murine models and 3) to evaluate the effect of oxidative stress on these muscles.MethodsC57BL6 mice were divided in two groups, with one group receiving 3 mg/kg intraperitoneal injections of edaravone (I/R + Ed group) and the other group receiving an identical amount of saline (I/R group) 30 minutes before ischemia. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a potent and novel synthetic scavenger of free radicals. This drug inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway, in addition to having potent antioxidant effects against ischemia reperfusion. The duration of the ischemia was 1.5 hours, with reperfusion at either 24 or 72 hours (3 days). Specimens of gastrocnemius (GC) and anterior tibialis (TA) were removed for histological evaluation and biochemical analysis.ResultsThis model of I/R injury was highly reproducible in histologic muscle damage. In the histologic damage score, the mean muscle fibers and inflammatory cell infiltration in the I/R + Ed group were significantly less than the corresponding values of observed in the I/R group. Thus, pretreatment with edaravone was observed to have a protective effect on muscle damage after a period of I/R in mice. In addition, the mean muscle injury score in the I/R + Ed group was also significantly less than the I/R group. In the I/R + Ed group, the mean malondialdehyde (MDA) level was lower than in the I/R group and western-blotting revealed that edaravone pretreatment decreased the level of inducible nitric oxide synthase (iNOS) expression.ConclusionsEdaravone was found to have a protective effect against I/R injury by directly inhibiting lipid peroxidation of the myocyte by free radicals in skeletal muscles and may also reduce the secondary edema and inflammatory infiltration incidence of oxidative stress on tissue.

Effects of edaravone pretreatment on pulmonary inflammatory response during selective lobar blockade in patients undergoing thoracotomy

Objective To investigate the effects of edaravone pretreatment on pulmonary inflammatory response during selective lobar blockade in patients undergoing thoracotomy,Methods Sixty ASA Ⅰ or Ⅱ patients of both sexes,aged 40-64 yr,weighing 50-80 kg,undergoing esophagectomy were randomly divided into 4 groups (n =15 each):the one-lung ventilation group (group OLV),the edaravone pretreatment + one-lung ventilation group (group E + OLV),the Univent tube selective lobar blockade group (group U) and the edaravone pretreatment + Univent tube selective lobar blockade group (group E + U).Padents in groups OLV and U were intubated with the double lumen endobronchial tube and Univent tube,respectively.Edaravone at a dose of 1 mg/kg was infused into patients at 5 min before one-lung ventilation in group E + OLV and before selective lobar blockade in group E + U,respectively.The patients in groups OLV and U received the equal volume of normal saline.The blood samples (5 ml ) were then drawn from the radial artery after anesthesia induction (T0),at 60 min after onelung ventilation (T1),at the end of operation (T2 ) and 120 min after operation (T3) for detecting the plasma concentrations of TNF-α,IL-6 and IL- 10 by enzyme-linked immunosorbent aesay.Results Compared with the group OLV and U,the plasma concentrations of TNF-α and IL-6 decreased at T2 and T3 in group E + OLV and group E + U (P ＜ 0.05).Condusion Edaravone pretreatment can reduce pulmonary inflammatory response during selective lobar blockade in patients undergoing thoracotomy. Key words: Free radical scavengers; Thoracic surgical procedures; Pulmonary ventilation; Inflam

Effects of edaravone pretreatment on the lung injury during one-lung ventilation

Objective To investigate the effects of edaravone pretreatment on the lung injury during onelung ventilation (OLV) in patients.Methods Forty ASA Ⅰ or Ⅱ male patients, aged 48-64 yr, with body mass index 18-26 kg/m2, undergoing elective resection of esophageal carcinoma, were randomly divided into 2 groups (n = 20 each): control group (group C) and edaravone group (group E). Anesthesia was induced with fentanyl,propofol and rocuronium and maintained with sevoflourane, remifentanil and atracurium. The patients were mechanically ventilated (during OLV VT 8 ml/kg, RR 15 bpm, I:E 1:1.5). In group E edaravone 0.5 mg/kg (in normal saline 100 ml) was infused over 30 min after skin incision. PETCO2 and peak airway pressure (Ppeak) were recorded during operation. Venous blood samples were obtained before opening the thoracic cavity and at the end of operation for determination of serum SOD activity and the levels of serum surfactant protein A (SP-A), MDA and TNF-α. Results There was no significant difference in PETCO2 and Ppeak during operation between the two groups (P ＞ 0.05). Serum SOD activity was significantly decreased, while the levels of serum SP-A, MDA and TNF-α were significantly increased after OLV in both groups (P ＜ 0.05). Serum SOD activity was significantly higher,while the levels of serum SP-A, MDA and TNF-α were significantly lower at the end of operation in group E than in group C (P ＜ 0.05). Conclusion Edaravone pretreatment can reduce the lung injury during OLV through inhibiting oxidative response and inflammatory response in patients. Key words: Free radical scavengers; Respiratory distress syndrome, adult; Respiration, artificial

A comparative study on the protection effect of nerve growth factor and edaravone pretreatment against cerebral ischemia/reperfusion injury

To compare the protective effect of nerve growth factor (NGF) and edaravone (a free radical scavenger) pretreatment against cerebral ischemia/reperfusion (I/R) injury to nerve cells. Cortical neurons of Sprague-Dawley (SD) mouse aged shorter than 24 hours were cultured for 7 days, then they were randomly divided into control group, I/R group, NGF of 10, 50, 100 microg/L pretreatment groups and 100 mumol/L edaravone pretreatment group. In pretreatment groups the cells were pretreated with drugs correspondingly. After culturing for 24 hours, glutamate of 200 mumol/L was given into the culture of all groups, except control group, for half an hour. Then culture medium in all groups were renewed with ordinary culture medium, and cultures were continued for 24 hours. The survival rate (by methyl thiazolyl tetrazolium assay), the content of lactate dehydrogenase (LDH, by spectrometry) and the rate of apoptosis (by flow cytometric) were determined. The cellular shape and ultrastructure were observed by hematoxylin-eosin (HE) staining and electronic microscopy correspondingly. The survival rate of nerve cells in NGF groups and edaravone group was significantly higher than that in I/R group [(0.21 + or - 0.04)%, (0.23 + or - 0.04)%, (0.21 + or - 0.04)%, (0.24 + or - 0.04)% vs. (0.19 + or - 0.04)%]. The content of LDH in culture medium and the rate of apoptosis in NGF groups and edaravone group were lower than those in I/R group (P<0.05 or P<0.01). The release rate of LDH in each group was (0.50 + or - 0.06)%, (0.46 + or - 0.07)%, (0.50 + or - 0.02)%, (0.43 + or - 0.06)% vs. (0.56 + or - 0.03)%, respectively. The rate of apoptosis in each group was (10.77 + or - 1.07)%, (10.38 + or - 0.70)%, (13.34 + or - 0.57)%, (9.99 + or - 0.77)% vs. (14.52 + or - 0.77)%, respectively. The cellular shape and ultrastructure of nerve cells in NGF groups and edaravone group were affected much less than that of I/R group. NGF of 50 microg/L pretreatment group gave the best effect among three groups. There was no significant difference between NGF 50 microg/L pretreatment group and edaravone pretreatment group. NGF and edaravone pretreatment 24 hours before cerebral I/R give protective effects against cerebral I/R injury. The protective effects are best in NGF of 50 microg/L pretreatment group and edaravone pretreatment group, and there is no significant difference between them.

Pretreatment with edaravone reduces lung mitochondrial damage in an infant rabbit ischemia-reperfusion model

Purpose Free radical scavenger edaravone has been approved as a new drug for treatment of stroke patients. The purpose of this study was to examine whether pretreatment with edaravone could attenuate ischemia-reperfusion (IR)–induced lung damage in infant rabbits. Methods New Zealand White rabbits (Experimental Animal Center, Nanjing Medical University, Nanjing, China) at age from 15 to 21 days were subjected to sham operation, IR, or edaravone plus IR. Ischemia/reperfusion was induced by clamping the right pulmonary hilum for 1 hour and then removal of the clamp for 4 hours. Edaravone (1 mg/kg, intravenous) was given 5 minutes before ischemia. Concentrations of reactive oxygen species-hydroxyl radical (ROS-HR) and malondialdehyde (MDA), and activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the lung tissue were measured. Mitochondrial membrane potential, swelling rate, and ultrastructure of the lung were analyzed, and histologic condition of the lung was evaluated. Results Edaravone pretreatment reduced markedly the productions of ROS-HR and MDA and increased the activities of GSH-PX and SOD. It attenuated both IR-induced decrease in mitochondrial membrane potential from 60% to 14% and IR-induced increase in mitochondrial swelling. As results, the mitochondrial and lung tissue damages were less, leading to an improved survival rate in IR rabbits pretreated with edaravone compared with IR rabbits without the treatment. Conclusion Edaravone pretreatment reduces the IR-induced lung mitochondrial damage in infant rabbits.