Effect of edaravone on renal injury in rats with aldosterone-induced hypertension / 中华麻醉学杂志

Objective:To evaluate the effect of edaravone on renal injury in rats with aldosterone-induced hypertension.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (S group), hypertension group (H group) and edaravone group (E group). The hypertension model was developed by subcutaneously embedding aldosterone osmotic pump (administration rate 0.75 μg·kg -1·h -1) for 4 weeks.After embedding osmotic pump subcutaneously, edaravone 10 mg/kg was injected via the tail vein every day for 4 consecutive weeks in E group, while normal saline 10 ml/kg was injected instead for 4 consecutive weeks in H group.BP-2010A noninvasive manometry device was used to measure the systolic pressure of tail artery before embedding osmotic pump and at 1, 2, 3 and 4 weeks after administration.After 4 weeks of administration, the 24 h urinary albumin concentration, plasma creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured, the bilateral kidneys were weighed, the right kidney weight/body weight ratio (RKW/BW) was calculated, the glomerular extramesangial matrix area/glomerular area ratio (M/G) was measured by PAS method, and the collagen volume fraction (CVF) was measured by Masson staining method, and the expression of aldosterone receptor (MCR) and type Ⅰ collagen in renal tissues was detected by Western blot. Results:Compared with group S, the systolic pressure was significantly increased, the concentrations of 24-h urinary albumin, plasma Cr and BUN were increased, the RKW/BW ratio, M/G and CVF were increased, and the expression of type Ⅰ collagen and MCR was up-regulated after embedding osmotic pump in group H ( P<0.05). Compared with group H, the systolic pressure was significantly decreased, the concentrations of 24-h urinary albumin, plasma Cr and BUN were decreased, the RKW/BW ratio, M/G and CVF were decreased, and the expression of type Ⅰ collagen and MCR was down-regulated after embedding osmotic pump in group E ( P<0.05). Conclusions:Edaravone can reduce renal injury in rats with aldosterone-induced hypertension, and the mechanism is related to down-regulation of MCR expression.

Relationship between edaravone-induced inhibition of pressure overload-induced myocardial remodeling and AT1R/MAPKs/StAR signaling pathway in rats / 中华麻醉学杂志

Objective:To evaluate the relationship between edaravone-induced inhibition of pressure overload-induced myocardial remodeling and angiotensin Ⅱ type 1 receptor (AT1R)/mitogen activated protein kinases (MAPKs)/steroidogenic acute regulatory protein (StAR) signaling pathway in rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 2 months, weighing 200-220 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), pressure overload group (POL group) and edaravone group (E group). The cardiac pressure overload was induced by ligation of thoracic aorta for 8 weeks.After the model preparation, 0.9% sodium chloride 10 ml/kg was intraperitoneally injected daily in group POL, and edaravone 10 mg/kg was given instead in group E for 8 consecutive weeks.After the model was successfully established, the left ventricular ejection fraction (EF) and ventricular shortening fraction (FS) were measured by two-dimensional ultrasound.The animals were sacrificed by bloodletting, and the heart weight/body weight ratio (HW/BW ratio) was calculated.Myocardial tissues were obtained for determination of the cross-sectional area (MSA) after HE staining, the collagen volume fraction (CVF) (using Masson′s staining), the expression of AT1R and StAR (by immunohistochemistry), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK phosphorylation levels (p-ERK1/2/ERK1/2 ratio and p-p38 MAPK/p38 MAPK ratio) (by Western blot) and the aldosterone content (by enzyme-linked immunosorbent assay). Results:Compared with group S, the HW/BW ratio, MSA and CVF were significantly increased, EF and FS were decreased, AT1R and StAR expression was up-regulated, and p-ERK1/2/ERK1/2 ratio, p-p38 MAPK/p38 MAPK ratio and aldosterone content were increased in group POL ( P<0.05). Compared with POL group, the HW/BW ratio, MSA and CVF were significantly decreased, EF and FS were increased, AT1R and StAR expression was down-regulated, and p-ERK1/2/ERK1/2 ratio, p-p38 MAPK/p38 MAPK ratio and aldosterone content were decreased in group E ( P<0.05). Conclusion:The mechanism of edaravone-induced inhibition of pressure overload-induced myocardial remodeling is probably associated with inhibiting the activation of AT1R/MAPKs/StAR signaling pathway in rats.

Comparative Evaluation of Efficacy and Safety of Herbal Preparation vis-a-vis Beclomethasone Cream on Radiation Induced Skin Injury in Head and Neck Carcinoma Patients Receiving Radiotherapy or Chemoradiation in Oncology Department at a Tertiary Care Hospital

Introduction: Radiation mitigators are the compounds whichcan minimize or ameliorate post irradiation-toxicity providedthey are administered before the onset of toxic symptoms.Hence, there is an urgent need to prevent harmful effectssecondary to ionizing radiations.Material and Methods: Sixty patients of Head and neckcarcinoma more than 18 years of age of either sex and willingto give informed consent were included in the study. In Group1, 30 patients received the Beclomethasone cream that wastopically applied from the day-1 of radiotherapy till 4-weeksafter completion of radiotherapy, whereas In Group-2, 30patients received the local application of the herbal paste fromthe day-1 of radiotherapy till 4-weeks after completion ofradiotherapy.Results: For measuring radiation-induced reactions, nonparametric test like chi-square test was applied and number ofpatients in different grades was calculated as per RTOGcriteria. Similarly for measuring radiation-induced mucosalreactions, chi-square test was applied and number of patientsin different grades was calculated as per RTOG-criteria.Conclusion: Present study revealed a marked beneficialeffects of herbal paste containing Azadirachta indica, aloevera, Ocimum sanctum and Curcuma longa on radiationinduced skin injury in patients with Head and neck carcinomaas compared to topical Beclomethasone cream.

In vitro antioxidant, antilipoxygenase and antimicrobial activities of extracts from seven climbing plants belonging to the Bignoniaceae / 中西医结合学报

<p><b>OBJECTIVES</b>This study aimed to evaluate the in vitro antioxidant capacity, to determine the anti-inflammatory effect due to lipoxygenase inhibition and to test the antimicrobial activity of ethanolic extracts from leaves of seven climbing species belonging to the Bignoniaceae family. These species are Adenocalymma marginatum (Cham.) DC., Amphilophium vauthieri DC., Cuspidaria convoluta (Vell.) A. H. Gentry, Dolichandra dentata (K. Schum.) L. G. Lohmann, Fridericia caudigera (S. Moore) L. G. Lohmann, Fridericia chica (Bonpl.) L. G. Lohmann and Tanaecium selloi (Spreng.) L. G. Lohmann.</p><p><b>METHODS</b>The antioxidant activity was evaluated using three methods, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power. Lipoxygenase-inhibiting activity was assayed spectrophotometrically; the result was expressed as percent inhibition. The antimicrobial activity was assessed using the agar disk diffusion method. Minimal inhibitory concentration (MIC) and minimal bactericidal/fungicidal concentration were also determined for each extract against 12 pathogenic bacterial strains of Staphylococcus aureus and seven fungal strains of the Candida genus. The identification of the major compounds present in the most promising extract was established by high-performance liquid chromatography-tandem mass spectrometry.</p><p><b>RESULTS</b>C. convoluta, F. caudigera, and F. chica exhibited the best antioxidant activity by scavenging DPPH and ABTS radicals and reducing Fe ion. These extracts showed a notable inhibition of lipoxygenase. F. caudigera was found to have the lower MIC value against S. aureus strains and six Candida species. The extracts of F. caudigera and C. convoluta were active even against methicillin-resistant S. aureus. C. convoluta had higher total phenol content, better antioxidant activity and superior anti-inflammatory and antimicrobial activity. The main phenolic compounds found in this extract were coumaric and hydroxybenzoic acid derivatives and glycosylated and nonglycosylated flavones.</p><p><b>CONCLUSION</b>Most of the extracts exhibited antioxidant activity as well as in vitro inhibition of lipoxygenase. The excellent antimicrobial activity of T. selloi and F. chica supports their use in traditional medicine as antiseptic agents. The extracts of F. caudigera and C. convoluta, both with notable biological activities in this study, could be used as herbal remedies for skin care. In addition, this study provides, for the first time, information about phenolic compounds present in C. convoluta.</p>

Actividad antioxidante del complejo de inclusión del extracto de semilla de Bixa orellana en ß-ciclodextrina obtenido por CO2 supercrítico / Antioxidant activity of the inclusion complex of Bixa orellana seeds extract in ß-cyclodextrin obtained by supercritical CO2

Antecedentes: los extractos de Bixa orellana son utilizados como colorante de alimentos, y presentan una actividad antioxidante de importancia farmacéutica. Su uso puede limitarse por su inestabilidad, donde el proceso de inclusión en ß-ciclodextrina (ß-CD) por fluido supercrítico con CO2 (FSC-CO2) es una alternativa para mediar esta desventaja. Objetivos: comparar diferentes condiciones de temperatura y presión de extracción por FSC-CO2, para determinar cuál de estas permite obtener un extracto de Bixa orellana con mayor actividad antioxidante, y evaluar el efecto de la inclusión en ß-CD, en dicha capacidad antioxidante. Métodos: se obtuvieron extractos por FSC-CO2 variando condiciones de presión y temperatura: (I) 3583 psi, 35°C, (II) 1413 psi, 35°C, (III) 2184 psi, 45°C, (IV) 5076 psi, 45°C, y (V) 2300 psi, 40°C. Se evaluó la actividad antioxidante de los extractos obtenidos mediante el método DPPH, determinando su IC50. Se realizó el complejo de inclusión en ß-CD del extracto que presentó la mayor actividad antioxidante, por el método FSC-CO2, y fue caracterizado por IR, DSC y RMN. Mediante análisis comparativo de los espectros de la ß-CD, extracto libre y el complejo extracto/ß-CD, se verificó el acomplejamiento, y se evaluó la capacidad antioxidante del complejo de inclusión. Resultados: el extracto con mayor actividad antioxidante se obtuvo bajo la condición de extracción IV, con un IC50 de 23,55 µg/ mL, seguido del extracto II (28,76 µg/mL), del extracto III (37,23 µg/mL), del extracto V (81,09 µg/mL) y del extracto I (193,82 µg/mL), los cuales presentaron diferencias significativas (P<0,01). Los espectros obtenidos por IR, DSC y RMN presentaron desplazamientos propios del proceso de encapsulamiento. El valor IC50 del complejo extracto/ß-CD fue de 104,84 µg/mL, siendo significativamente mayor al valor obtenido para el extracto puro (23,55 µg/mL). Conclusión: el extracto de Bixa orellana con una actividad antioxidante mayor se obtuvo por fluido supercrítico a 5076 psi de presión y 45°C de temperatura. Las variaciones de los espectros IR, DSC y RMN demuestran la inclusión del extracto en la ß-CD, y los valores de IC50 indican el efecto protector de la ß-CD ante la reacción con el radical DPPH.

Background: Bixa orellana extracts are used to food coloring and it is important in pharmaceutical industry as a potential source of antioxidant activity. The application may be limited because it is unstable, but the process of inclusion in ß-cyclodextrin (ß-CD) by supercritical fluid CO2 (FSC-CO2) is an alternative to mediate this disadvantage. Objectives: we compared different conditions of temperature and pressure of FSC-CO2 extraction, to obtain a Bixa orellana extract with excellent antioxidant activity, and we evaluated the effect of inclusion in ß-CD in the antioxidant capacity. Methods: extracts were obtained by FSC-CO2 with different conditions of pressure and temperature: (I) 3583 psi, 35°C, (II) 1413 psi, 35°C, (III) 2184 psi, 45°C, (IV) 5076 psi, 45°C, and (V) 2300 psi, 40°C. The antioxidant activity by DPPH assay was determined and the IC50 was evaluated. We performed the inclusion complex in ß-CD with the highest antioxidant activity extract. The extract/ß-CD complex was characterized by IR, DSC and NMR. This complexation was verified by comparative analysis of the spectra of the ß-CD, free extract and ß-CD/extract complex. The antioxidant capacity of this inclusion complex was evaluated. Results: the extract with highest antioxidant activity was obtained under the extraction condition IV, with an IC50 of 23.55 µg/mL, followed extract II (28.76 µg/mL), extract III (37.23 µg/mL), extract V (81.09 µg/mL) and extract I (193.82 µg/mL). Analysis showed significant differences (P<0.01) between these extracts. The spectra obtained by IR, DSC and NMR evidence the encapsulation process. The IC50 value of the extract/ß-CD complex (104.84 µg/mL) was significantly higher than the value obtained for the pure extract (23.55 µg/mL). Conclusions: the highest antioxidant activity of Bixa orellana extracts was obtained by supercritical fluid pressure at 5076 psi and temperature of 45°C. Variations in IR, DSC and NMR spectra showed the inclusion of the ß-CD/extract, and the IC50 values indicated the protective effect of ß-CD to the reaction with DPPH radical.

Edaravone protects against cerebral ischemia-reperfusion injury in rats by upregulation of the LMO4 expression / 国际脑血管病杂志

ObjectiveTo investigate the neuroprotective mechanism of edaravone for cerebral ischemia-reperfusion injury in rats.MethodsThirty-six healthy adult male SD rats were randomly divided into three groups: a sham operation group, an ischemic model group, and an edaravone group (n=12 in each group).A focal cerebral ischemia model was induced by the suture method.Reperfusion was resumed after 2 h of ischemia;then the animals were sacrificed at 24 h after reperfusion.Edaravone 3 mg/kg was injected intraperitoneally immediately after cerebral ischemia-reperfusion in the edaravone group.The rats in the model group were injected equal volume normal saline.HE staining was used to observe the pathological changes.TUNEL staining was used to detect apoptotic cells in the ischemic cortex.Western blot and immunofluorescent staining were used to detect the expression levels of LIM domain protein 4 (LMO4) and LMO4 positive cells.Results HE staining showed that cellular morphology was basically normal in the sham operation group;both the model group and edaravone group had cell necrosis, but the latter was less severe.The number of morphologically normal cells in the edaravone group was significantly more than that in the model group (P<0.01).TUNEL staining showed that no TUNEL positive cells in the sham operation group were observed.The TUNEL positive cells in the edaravone group was significantly less that in the model group (P<0.01).Immunofluorescence staining showed that the expression level of LMO4 in the ischemic cortex in the edaravone group was significantly higher than that in the model group (P<0.01).ConclusionsEdaravone can alleviate the cerebral ischemia-reperfusion injury and inhibit neuronal apoptosis.Its mechanism may be associated with the upregulation of LMO4 expression.

The effects of nimodipine combined with edaravone on vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage / 国际脑血管病杂志

Objeetive To investigate the effects of nimodipine combined with edaravone on cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH).Methods The consecutive patients with aSAH who underwent microsurgical clipping were included retrospectively.All patients received intravenous prophylaxis with nimodipine,and some patients also used edaravone (30 mg,twice a day for 2 weeks).They were divided into either a CVS group or a non-CVS group according to the findings of transcranial Doppler.They were also divided into a DCI group and a non-DCI group according to the findings of CT reexamination and clinical examination.The demographics,baseline clinical data,Glasgow Coma Scale (GCS) score,Fisher grade,Humt-Hess grade,and aneurysm location of all patients were collected.The multivariate logistics regression analysis was used to identify the independent risk factors for CVS and DCI.Results A total of 220 patients with aSAH were enrolled in the study,132 (60.0％) had CVS and 106 (48.2％) had DCI.One hundred twenty-three patients (55.9％)were treated with nimodipine + edaravone,97 were treated with nimodipine alone,none of them died.The incidences of CVS (51.2％ vs.71.1％;x2 =8.962,P =0.003) and DCI (35.0％ vs.65.0％;x2 =19.535,P ＜0.001) in patients receiving nimodipine + edaravone therapy were significantly lower than those receiving nimodipine alone.The proportions of hypertension,hyperlipidemia,diabetes,smoking,high Fisher grade in the CVS group were significantly higher than those in the non-CVS group (all P ＜0.05),while the proportion of patients receiving nimodipine + edaravone therapy (47.7％ vs.68.2％;g2 =8.962,P =0.003) and the GCS score (11.2 ±3.1 vs.13.4 ±2.6;t =5.492,P＜0.001) were significantly lower than those in the non-CVS group.Multivariate logistic regression analysis showed that low GCS score (odds ratio [OR] 6.57,95％ confidence interval [CI] 1.04-12.96;P=0.001),high Fisher grade (OR 5.39,95％ CI 4.09-20.15;P =0.004),hyperlipidemia (OR 4.39,95％ CI 2.97-34.15;P =0.004),hypertension (OR 3.24,95％ CI 1.06-13.47;P=0.016) were the independent risk factors for CVS,while received nimodipine + edaravone was the independent protective factor for CVS (OR 0.39,95％ CI0.13-0.91;P =0.039).The proportions of patients with hypertension,hyperlipidemia,diabetes,smoking,and high Fisher grade in the DCI group were significantly higher than those in the non-DCI group (all P ＜0.05),while the proportion of patients received nimodipine + edaravone (40.6％ vs.70.2％;x2 =19.535,P ＜ 0.001) and the GCS score (10.2 ± 2.4 vs.13.8 ± 2.6;t =10.648,P ＜ 0.001) were significantly lower.Multivariate logistic regression analysis showed that low GCS score (OR 8.92,95％ CI 2.48-26.94;P =0.001),high Fisher grade (OR 7.49,95％ CI 1.96-20.47;P =0.001) were the independent risk factors for DCI,while.received nimodipine +edaravone was an independent protective factor for DCI (OR 0.27,95％ CI 0.08-0.97;P =0.020).Conclusions Compared with nimodipine alone,nimodipine combined with edaravone can significantly reduce the incidences of CVS and DCI.The GCS score,high Fisher grade,and hypertension are the independent risk factors for CVS and DCI in patients with aSAH,and nimodipine combined with edaravone is the independent protective factor for CVS and DCI.

Edaravone Enhances the Viability of Ischemia/reperfusion Flaps / 华中科技大学学报（医学）（英德文版）

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion (IR) and its mechanism.Forty-eight adult male SD rats were randomly divided into 3 groups:control group (n=16),IR group (n=16),and edaravone-treated IR group (n=16).An island flap at left lower abdomen (6.0 cm×3.0 cm in size),fed by the superficial epigastric artery and vein,was created in each rat of all the three groups.The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h,and then the blood perfusion was restored.From 15 min before reperfusion,rats in the edaravone-treated IR group were intraperitoneally injected with edaravone (10 mg/kg),once every 12 h,for 3 days.Rats in the IR group and control group were intraperitoneally injected with saline,with the same method and frequency as the rats in the edaravone-treated IR group.In IR group and edaravone-treated IR group,samples of flaps were harvested after reperfusion of the flaps for 24 h.In the control group,samples of flaps were harvested 34 h after creation of the flaps.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined,and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin (HE) staining,apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay,and the apoptotic rate of cells in vascular wall was calculated.The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy (TEM).Seven days after the operation,we calculated the flap viability of each group,and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels.The results showed that the content of MDA,the number ofmulticore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group.The activity of SOD,flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group.All the differences were statistically significant.The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group.It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels,which is related to scavenging oxygen free radicals,reducing the consumption of SOD,reducing the extent of lipid peroxidation and inflammation,and protecting functional structure of vessels in the early stages of reperfusion.

Free Radical Scavenging and Cyto-protective Activity of Ethanolic Extract of Nigella Sativa Seeds

Introduction: Free radicals and the oxidative stress have been implicated in a large number of chronic disorders such as Diabetes mellitus and its late complications, Cardio vascular disease, Arthritis also in some acute conditions such as the hemolytic disease in Glucose 6 Phosphate Dehydrogenase (G 6 PD) deficiency, where free radicals play a direct cytotoxic role causing cellular damage. Various exogenous substances have been found to be of great use for the purpose of scavenging free radicals. These includes micro nutrients such as vitamins eg. Vit C, Vit A etc or other dietary agents polyphenols, flavenols, tannins etc. In traditional medicine certain food items and their extracts are considered useful in combating conditions such as diabetes mellitus, Cardio vascular diseases etc and their long term complications that are caused by oxidative stress. Nigella Sativa seeds are one such condiment used in food in south east, central Asia and middle east and also used in ancient Indian (Ayurveda) and Greeko-arabic (Unani) systems of medicine. Material and Method: The objective of this study is to quantify the free radical scavenging and Cytoprotective effects of ethanolic extract of Nigella Sativa seeds. To measure the free radical scavenging activity DPPH free radical scavenging assay was used. To measure cyto-protective effects of Nigella Sativa seed extract, an AAPH assay was used with the Cyto-protective effect being measured on RBCs (Red blood cells) suspended in PBS buffer. Results: In the DPPH assay the ethanolic extract of Nigella Sativa seeds showed significant free radical scavenging activity. The activity was concentration dependent. Conclusion: In AAPH RBC lysis assay the ethanolic extract of Nigella Sativa seeds did show considerable protective effect against AAPH induced RBC lysis. Once again the activity was concentration dependent.

Effect of edaravone pretreatment on oxidative stress and inflammatory reaction during one lung ventilation of patients underwent thoracoscopic surgery / 临床麻醉学杂志

Objective To observe the effect of edaravone pretreatment on the lung injury during one lung ventilation of patients undergoing thoracoscopic surgery.Methods Forty male patients diagnosed of lung cancer (aged 47-65 years,height 165-183 cm,weight 64-85 kg,BMI<30 kg/m2 ,ASA gradeⅠorⅡ)who were scheduled for thoracoscopic pulmonary resection surgery were randomly divided into two groups(n =20 each):control group (group C)and edaravone group (group E).In group E edaravone 30mg(dissolution in normal saline 100 ml)was administered within 30 min before surgery.In group C nor-mal saline 100 ml was administered within the same time.PET CO2 and peak airway pressure (Pmax)were recorded during operation,venous blood samples were taken before skin incision and at the end of operation for detection of the concentration of IL-8,IL-10,TNF-α and SP-A.Results There were no significant difference in PET CO2 and Pmax between the two groups..Compared with T1 ,concentration of IL-8,IL-10, TNF-αand SP-A all increased significantly in both groups on T6 (P <0.05).Compared with group C,IL-8, TNF-αand SP-A levels of T6 in group E were lower significantly (P < 0.05 ).There was no significant differences in the levels of IL-10 between the two groups.Conclusion Edaravone can inhibit oxidative stress and inflammatory reaction during one lung ventilation in patients underwent thoracoscopic surgery.

Clinical Effect of edaravone on serum superoxide dismutase and malondialdehyde levels in elderly transient ischemic attack / 中华老年医学杂志

Objective To investigate the clinical effect of Edaravone on transient ischemic attack and serum superoxide dismutase and malondialdehyde levels in the elderly.Methods Ninety eight cases with transient ischemic attack treated in our hospital were chosen as the objects, which were randomly divided into observation group and control group (n=49 for each).Patients in observation group were treated with Edaravone combined with conventional therapy, and patients in control group were treated with conventional therapy.The clinical effect and levels of SOD and MDA were analyzed and compared between the two groups.Results The effective rate and total efficiency were higher in observation group than in control group (79.6％ vs.55.1％, 95.9％ vs.83.7％, x2 =6.914 and 4.354, P=0.008 and 0.032).The SOD level was higher and the MDA level was lower in observation group than in control group (both P＜0.001) after treatment.Conclusions Edaravone could improve the symptoms of transient ischemic attack in the elderly, and increase the activity of SOD and reduce MDA level, which is helpful to reduce lipid peroxides, alleviate free radical toxicity, and improve the anti-oxidation ability.

In vitro antioxidant capacity and free radical scavenging evaluation of active metabolite constituents of Newbouldia laevis ethanolic leaf extract

BACKGROUND: The aim of the present study was to evaluate the in vitro antioxidant and free radical scavenging capacity of bioactive metabolites present in Newbouldia laevis leaf extract. RESULTS: Chromatographic and spectrophotometric methods were used in the study and modified where necessary in the study. Bioactivity of the extract was determined at 10 µg/ml, 50 µg/ml, 100 µg/ml, 200 µg/ml and 400 µg/ml concentrations expressed in % inhibition. The yield of the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of bioactive metabolic constituents gave high levels of ascorbic acid (515.53 ± 12 IU/100 g [25.7 mg/100 g]), vitamin E (26.46 ± 1.08 IU/100 g), saponins (6.2 ± 0.10), alkaloids (2.20 ± 0.03), cardiac glycosides(1.48 ± 0.22), amino acids and steroids (8.01 ± 0.04) measured in mg/100 g dry weight; moderate levels of vitamin A (188.28 ± 6.19 IU/100 g), tannins (0.09 ± 0.30), terpenoids (3.42 ± 0.67); low level of flavonoids (1.01 ± 0.34 mg/100 g) and absence of cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-), iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen (1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a concentration-dependent antioxidant activity with no significant difference with the controls. Though, IC50 of the extract showed significant difference only in singlet oxygen (1O2) and iron chelating activity when compared with the controls. CONCLUSIONS: The extract is a potential source of antioxidants/free radical scavengers having important metabolites which maybe linked to its ethno-medicinal use.

Effect of edaravone on apoptosis in hippocampal cells in a rat model of endotoxic shock / 中华麻醉学杂志

Objective To evaluate the effect of edaravone on apoptosis in hippocampal cells in a rat model of endotoxic shock.Methods Thirty-six male Sprague-Dawley rats, weighing 200-250 g, aged 6 weeks, were randomly divided into 3 groups (n=12 each) using a random number table: control group (group C), endotoxic shock group (group ES), and edaravone group (group E).Lipopolysaccharide 10 mg/kg was injected via the femoral vein to establish the model of endotoxic shock in ES and E groups, while the equal volume of normal saline was given in group C.In group E, edaravone 3 mg/kg was intravenously injected immediately after establishment of the model once every 2 h until the animals were sacrificed.The equal volume of normal saline was given instead of edaravone in C and ES groups.At 6 and 12 h after administration of edaravone, 6 rats in each group were sacrificed, and the hippocampi were isolated for determination of malondialdehyde (MDA) content (using thiobarbituric acid method) , tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents (using enzyme-linked immunosorbent assay), and cell apoptosis in hippocampal CA1 region (by TUNEL assay).The apoptotic index was calculated.Results Compared with group C, the MDA, TNF-α and IL-6 contents were significantly increased at 6 and 12 h after administration of edaravone, and the apoptotic index was increased at 12 h after administration of edaravone in ES and E groups.Compared with group ES, the MDA, TNF-α and IL-6 contents were significantly decreased at 6 and 12 h after administration of edaravone, and the apoptotic index was decreased at 12 h after administration of edaravone in group E.Conclusion Edaravone can reduce apoptosis in hippocampal cells, and the mechanism is associated with the reduced oxidative stress and inflammatory responses in a rat model of endotoxic shock.

Effect of reactive oxygen species on dorsal root ganglion P2X3 receptor-induced pain signal / 第二军医大学学报

Objective To investigate the effect of reactive oxygen species(ROS) on P2X3 receptor-mediated neuropathic pain. Methods Neuropathic pain model was induced in female Sprague Dawley rats by chronic compression of dorsal root ganglia (CCD), and the CCD rats were randomly divided into 4 groups (each group containing 10 rats): Saline group (NS group); PBN 100 mg/kg treatment group; PBN 30 mg/kg treatment group; and PBN 10 mg/kg treatment group. The specific agonist of P2X3 receptor, α, β-meATP (50 nmol in 50 μL), was subcutaneously injected into the plantar surface of the right hind paws of each rat 30 minafter PBN or NS injection. The spontaneous paw flinching times and withdrawing time were observed for 15 min after injection and the paw lift time per minute (PLTPM) in every 2 minutes was calculated. Results Pre- treatmentwith PBN inhibited α, β-meATP-induced spontaneous pain in a dose-dependent manner. Compared with the NS group, PBN 100 mg/kg group significantly inhibited flinching response during the first 6 min (P<0. 05), while the rats in PBN 30 mg/kg group only had significantly attenuated flinching response during the second to the fourth minute compared with NS group(P<0. 05). Conclusion Oxygen free radical scavenger can effectively alleviate the neuropathic pain caused by CCD and P2X3 receptor agonist-induced spontaneous pain. ROS may act as a messenger in P2X3 receptor-mediated pain signaling transmission.

Ultrastructural changes in a rat model of lower limb ischemia/reperfusion injury undergoing edaravone / 中国组织工程研究

BACKGROUND:The oxygen free radicals and apoptosis play an important role in limb ischemia/reperfusion injury, so we can al eviate limb ischemia/reperfusion injury by inhibiting the production of oxygen free radicals and apoptosis. OBJECTIVE:To discuss the application and effect of edaravone on limb ischemia/reperfusion injury in rats. METHODS:Of the 30 female Sprague-Dawley rats, 20 rats were randomly selected to make models of limb ischemia/reperfusion injury by ligating the root of right lower limb with a self-made bal oon cuff at 40 kPa pressure to block blood flow for 4 hours and reperfusing. After success model establishment, they were randomly assigned to two groups. In the edaravone perfusion group, edaravone 3 mg/kg was injected via the left femoral vein at 5 minutes before reperfusion. In the model group and normal group (the remaining 10 rats), an equal volume of physiological saline was given at the same time point. At 24 hours after reperfusion, the right anterior tibial muscle of each group was removed and these ultrastructural changes were observed by transmission electron microscope. Bcl-2 mRNA and Bax mRNA of rat anterior tibial muscle of each group were semiquantitatively detected with the RT-PCR and the ratio of bcl-2/bax was calculated. RESULTS AND CONCLUSION:(1)Electron microscope results:compared with the model group, the muscle fibers were neater;the M line and the N line were clearer;the swel ing of mitochondria was al eviated;the numbers of mitochondria and mitochondrial crista were also increased in the edaravone perfusion group. (2)RT-PCR results:At 24 hours after reperfusion, the relative expression of bcl-2 mRNA and the ratio of bcl-2 mRNA to bax mRNA in right anterior tibial muscle were lower in the model group compared with the edaravone perfusion group (P<0.05). However, relative expression of bax mRNA was greater in the model group than that in the edaravone perfusion group, which were both higher than the normal group (P<0.05). Results indicated that the free radical scavenger edaravone relieved limb ischemia/reperfusion injury by improving the mitochondrial ultrastructure and promoting expression of bcl-2 mRNA and inhibiting expression of bax mRNA, and could provide a new choice for the treatment of limb ischemia/reperfusion injury.

Role of free radical scavengers in oral malignancies treated with radiotherapy.

Background: Radiotherapy has an important role in treatment of oral cancer, but it causes some deleterious effect on healthy cells. Radiation produces free radicals which cause lipo-peroxidation, alteration of protein, and DNA damage, and eventually cell death. This study is designed to evaluate protective role of antioxidants in oral malignancies treated with radiotherapy. Methods: This study is conducted in patients of oral cancer treated with radiotherapy. Patients were divided into two groups, control (n=7) and test (n=9). Patients in control group treated with radiotherapy alone and in test group were supplemented with oral antioxidants throughout the radiotherapy course. Pre and post radiotherapy levels of MDA, SOD and Glutathione reductase were measured in blood and cancerous tissue in both groups and statistically compared. TNM staging before and after radiotherapy and side effects of radiotherapy were also compared in both groups. Results: On statistical comparison of mean difference values of MDA, SOD & GR of control v/s test group, it was noticed that there was a significant reduction in MDA (p<0.05) and significant increase in GR levels (p<0.05) but non significant increase in SOD levels (p>0.05) in test group in comparison to control group for both blood and tissue levels. TNM status of patients improved significantly after radiotherapy in test group. Comparison of side effects between both groups indicated that there was reduction in side effects in test group after radiotherapy. Conclusion: These findings indicated the protective role of antioxidants against free radicals produced in oral malignancies treated with radiotherapy.

Actividad antioxidante de clones de cacao (Theobroma cacao l. ) finos y aromáticos cultivados en el estado de Chiapas, México / Antioxidant activity of clones of cocoa (Theobroma cacao L.) fine and aromatic grown in the state of Chiapas-México

Objetivo: determinar la capacidad antioxidante y contenido de grasa de clones de cacao, provenientes de especies nativas del Estado de Chiapas, México. Materiales y métodos: en extractos de 34 muestras semillas de cacao diluidas en metanol al 95% y clasificadas según pH en tres grupos: I (5,52-5,90), II (5,91- 6,28) y III (6,29-6,67), se realizaron ensayos analíticos de variables físicas y químicas. Se evaluó la inhibición de radicales 2,2-difenil-2-picrilhidrazil (DPPH) a 517 nm, el contenido de polifenoles mediante el reactivo de folin-ciocalteu (FCR) a 765 nm y cantidad de grasas totales según método AOAC. Se aplicó un ANOVA al nivel del 95%, con post prueba Tukey para comparar de medias muestrales y determinar diferencias significativas (p<0.05), además de sus correlaciones lineales. Resultados: El Grupo I con menor pH, mostró menor contenido calórico (26,3±3,6% de grasas), posee la mejor actividad antioxidante con menor valor EC50 de 4182 ppm y mayor contenido de polifenoles 6,6±0,32 equivalentes de ácido gálico por 100 g de muestra seca. Conclusión: El cacao chiapaneco posee importantes ventajas competitivas en el mercado, por su calidad como alimento funcional-nutracéutico y como materia prima para la industria alimentaria, fuente de antioxidantes y aditivos naturales, con potencial consumo en la industria farmacéutica y cosmética internacional.

Objective: To determine antioxidant capacity and fat content of cacao clones from the State of Chiapas, Mexico. Materials and Methods: 34 cocoa beans samples were diluted in 95% methanol and classified by pH in: group I (5.52-5.90), group II (5.91- 6.28), and group III (6.29-6.67). Chemical and physical analysis were developed. 2,2- diphenyl-2-picrylhydrazyl (DPPH) inhibition was evaluated at 517 nm. Polyphenol and fat contents were evaluated by Folin-Ciocalteu Reagent at 765 nm and AOAC method, respectively. Differences in variables were evaluated by ANOVA and Tukey test, in addition to its linear correlations. Results: Group I showed the lowest caloric content (26.3±3.6% fat), the best antioxidant activity with lower EC50 value of 4182 ppm and the highest polyphenol content (6.6±0.3 gallic acid/100 g dry sample). Conclusion: Chiapas cocoa has significant competitive advantages due to its quality as a functional and nutraceutical food. It is a good raw material for food industry because it is a good source of antioxidants and natural additives. Furthermore, it is a potential ingredient in the international pharmaceutical and cosmetic industry.

Effect of edaravone on permeability of blood-brain barrier in septic rats / 中华麻醉学杂志

Objective To evaluate the effects of edaravone on the permeability of blood-brain barrier in septic rats.Methods Ninety male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 3 groups (n=30 each):control group (group C),sepsis group (group lipopolysaccharide (LPS)) and edaravone group (group E).Sepsis was induced by injection of LPS 10 mg/kg via the femoral vein in LPS and E groups.After LPS injection,edaravone 3.0 mg/kg was injected intravenously every 2h for 7 times in group E.The equal volume of normal saline was administered instead of edaravone in C and LPS groups.At 2,6 and 12h after LPS injection,5 rats were chosen and Evan's blue (EB) was injected via the femoral vein,and then the rats were sacrificed and brain tissues were removed for determination of EB and water contents.Another 5 rats were chosen and blood samples were taken from the femoral artery for measurement of serum MDA concentration,and then the rats were sacrificed and the brain tissue was harvested for microscopic examination.Results Compared with group C,brain water and EB contents were significantly increased at 6 and 12h after LPS injection,and the serum MDA concentration was increased at 2,6 and 12h after LPS injection in LPS and E groups (P ＜ 0.05).Compared with group LPS,brain water and EB contents were significantly decreased at 6 and 12h after LPS injection,and serum MDA concentrations were decreased at 2,6 and 12h after LPS injection in group E (P ＜ 0.05).Sepsis-induced pathological changes were significantly attenuated in group E.Conclusion Edaravone can decrease the permeability of blood-brain barrier,attenuate brain edema and brain injury in septic rats,and reduction of oxygen free radical production may be involved in the mechanism.

Effect of edaravone on myocardial injury in patients undergoing off-pump coronary artery bypass grafting / 中华麻醉学杂志

Objective To evaluate the effect of edaravone on myocardial injury in patients undergoing offpump coronary artery bypass grafting (OPCABG).Methods Forty ASA physical status Ⅲ-Ⅳ patients,aged 45-64 yr,weighing 55-95 kg,with NYHA class Ⅱ-Ⅲ,scheduled for elective OPCABG,were randomly divided into 2 groups (n =20):edaravone group (group E) and control group (group C).After induction of anesthesia,edaravone 60 mg (in 100 ml of normal saline) was infused over 30 min in group E,while the equal volume of normal saline was given instead of edaravone in group C.Venous blood samples were taken before operation (T1),after skin incision (T2),at the end of operation (T3),and at 24 h after operation (T4) to measure the serum levels of myocardial enzymes and cardiac troponin Ⅰ (cTnI).The time for ventilator treatment,duration of stay in the intensive care unit and duration of stay in hospital were recorded.Results Compared with group C,the activities of serum creatine kinase,creatine kinase isoenzyme-MB,aspartate aminotransferase and lactate dehydrogenase and cTnI concentrations were significantly increased at T3 and T4 (P ＜ 0.05) and no significant changes were found at T1 in group E (P ＞ 0.05).The parameters mentioned above were significantly higher at T3 and T4 than at T1 in the two groups (P ＜ 0.05).The time for ventilator treatment,duration of stay in the intensive care unit and duration of stay in hospital were significantly shortened in group E as compared with group C (P ＜ 0.05 or 0.01).Conclusion Edaravone 60 mg infused before OPCABG can provide effective myocardial protection in patients.

Effects of edaravone postconditioning and remote ischemic postconditioning on myocardial ischemia/reperfusion injury in rats / 中华麻醉学杂志

Objective To evaluate the effects of edaravone postconditioning and remote ischemic postconditioning on myocardial ischemia/reperfusion (I/R) injury in rats.Methods Forty male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S); group I/R; edaravone postconditioning group (group E); remote ischemic postconditioning group (group P); edaravone postconditioning and remote ischemic postconditioning group (group EP).Myocardial I/R was induced by occlusion of anterior desending branch of left coronary artery for 30 min followed by 180 min reperfusion.Edaravone 3 mg/kg was injected intravenously at 1 min before reperfusion in groups E and EP.The animals underwent 10 min ischemia of bilateral hind limbs starting from 20 min of myocardial ischemia in groups P and EP.Left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP) and ± dp/dtmax were measured and recorded during reperfusion.Results Compared with group S,LVSP and ± dp/dtmax were significantly decreased and LVEDP was increased in the other groups (P ＜ 0.05).LVSP and ± dp/dtmax were significantly higher and LVEDP was lower during reperfusion in groups E,P and EP than in group I/R,and in group EP than in groups E and P (P ＜ 0.05).Conclusion Edaravone postconditioning and remote ischemic postconditioning can alleviate myocardial I/R injury and offers better efficacy than either alone.