Effect of ω-3 polyunsaturated fatty acid on oxidative stress production and apoptosis in hippocampus of neonatal rats with brain injury induced by lipopolysaccharide / 新乡医学院学报

Objective To investigate the effects of ω-3 polyunsaturated fatty acid(PUFA)on oxidative stress produc-tion and apoptosis in hippocampus of neonatal rats with brain injury induced by lipopolysaccharide(LPS). Methods Forty-eight neonatal Sprague Dawley rats(3 days)were randomly divided into control group,LPS group,ω-3 PUFA group and ω-6 PUFA group,with 12 rats in each group. The rats in the LPS group,ω-3 PUFA group and ω-6 PUFA group were given 0. 6 mg·kg - 1 LPS via intraperitoneal injection,then equal volume of saline,ω-3 PUFA and ω-6 PUFA was immediately given via intraperitoneal injection respectively;while the rats in the control group were all given equal volume of saline. The rats in each group were sacrificed at 24 hours after intraperitoneal injection with saline or fat emulsions to obtain the hippocampus. The levels of superoxide dismutase(SOD)and malondialdehyde(MDA),reduced glutathion(GSH),oxidized glutathione(GSSG) were detected and GSSG/ GSH was calculated. The apoptotic index was measured by terminal deoxynucleotidyl transferase-me-diated dUTP nick end labeling. Results Compared with the control group,the levels of SOD and GSH in hippocampus of rats in the LPS group,ω-6 PUFA group and ω-3 PUFA group were significantly decreased(P < 0. 05),and the levels of MDA, GSSG and the ratio of GSSG/ GSH were significantly increased(P < 0. 05). Compared with the LPS group,the levels of SOD and GSH in hippocampus of rats in ω-6 PUFA group were significantly decreased(P < 0. 05),the levels of MDA,GSSG and the ratio of GSSG/ GSH were significantly increased(P < 0. 05);the levels of SOD and GSH in hippocampus of rats in ω-3 PU-FA group were significantly increased(P < 0. 05),the levels of MDA,GSSG and the ratio of GSSG/ GSH were significantly de-creased(P < 0. 05). Compared with the ω-6 PUFA group,the levels of SOD and GSH in hippocampus of rats in ω-3 PUFA group were significantly decreased(P < 0. 05),the levels of MDA,GSSG and the ratio of GSSG/ GSH were significantly in-creased(P < 0. 05). The apoptotic index in the LPS group,ω-6 PUFA group and ω-3 PUFA group was higher than that in the control group(P < 0. 05). The apoptotic index in the ω-6 PUFA group was higher than that in the LPS group(P < 0. 05). The apoptotic index in the ω-3 PUFA group was lower than that in the LPS group and ω-6 PUFA group(P < 0. 05). Conclusion ω-3 PUFA can alleviate the oxidative stress,and decrease the apoptosis of hippocampus in neonatal rats with brain injury in-duced by LPS. So it has a neuroprotective effect in brain injury induced by LPS.

Neu-P11 reduces IOP through inhibiting oxidative stress level of acute high IOP rats / 中国药理学通报

Aim To explore the effect of Neu-P11,a novel melatonin agonist with similar function of melatonin,on IOP of acute high IOP animals and the related mechanism.Methods The experiment used the Trendelenburg position(head low feet high position of 80°)to establish acute high IOP model.Rats were placed in the Trendelenburg position and used Tonopen XL contact tonometer to measure IOP(every 5 minutes measured once IOP,and the maximum value in 20 minutes)in 8 :00～9 :00 am.And then,thirty Sprague-Dawley rats(8 week-old)were divided into five groups: normal IOP+normal saline,high IOP+normal saline,high IOP+10 mg·kg-1 Mel,high IOP+20 mg·kg-1 Neu-P11,high IOP+50 mg·kg-1 Neu-P11.Put in a flat to rest 2 h,animals were placed in Trendelenburg position again and then,IOP was measured every hour in the flat by 6 hours.After excessive sodium pentobarbital administration continuous for 1 week,the serum was collected and stored for subsequent detection at the end of the experiment.The level of MDA,SOD and GSH-Px enzyme activity of the rat serum was tested by kit accordingly.HE staining method was used to identify the SD rat retinal morphological changes.Results Trendelenburg position could induce IOP of model group rats,which was increased by 202.9％(P<0.01)and the content of MDA,reduced the activity of SOD and GSH-Px enzyme,retinal thickening was observed and its level was not clear.Neu-P11/Mel could significantly improve oxidative stress level and retinal edema in rats.Conclusion Neu-P11 could reduce IOP of the acute high IOP animals,which might be involved in the lower level of oxidative stress in the body.

Neuroprotective Effect of Ginsenoside Rg1 on Oxidative Damage Induced by Oxygen-glucose Deprivation and Reperfusion in Cultured Hippocampal Cells / 中国康复理论与实践

@#Objective To explore the effect of Ginsenoside Rgl on glutathion (GSH) level and glutathion peroxidase (GPx) activity after oxygen-glucose deprivation/reperfusion in cultured hippocampal cells. Methods The model of oxygen-glucose deprivation and reperfusion were established with the hippocampal neurons of rats. They were randomly divided into control group, model group and Ginsenoside Rgl treatment groups (5 μmol/L, 20 μmol/L, 60 μmol/L). The GSH level and GPx activity were measured 6 h after reperfusion. The apoptosis and the metabolic rate of methyl thiazolyl tetrazolium (MTT) were detected 24 h after reperfusion. Results Compared with model group, the GSH level, GPx activity, and metabolic rate of MTT improved (P<0.001), and the apoptosis decreased in the Ginsenoside Rgl groups (P<0.001) except with the dosage of 5 μmol/L (P>0.05). Conclusion Ginsenoside Rgl can protect the brain from ischemia by increasing the GSH level and GPx activity.

Protective effect of high expression of glutathione peroxidase on cell model of Alzheimer disease / 中华老年医学杂志

Objective To study the effects of eliminating free radical and increasing antioxidative capacity of glutathione peroxidase 1(GPX1) on PC12 cells. MethodsGPX1 recombinant plasmid and Plncxplasmid were transfected into PC12 cells and PC12 cells highly-expressing GPX1 stably were sieved by G418 solution. PC12 ceils were treated with different concentrations of amyloid β-protein (Aβ25-35) for 48 h, to decide the optimal concentration of Aβ25-35 and construct ideal cell model. GPX1/pLNCX/PC12 group, pLNCX/ PC12 group and PC12 group were treated with optimal concentration of Aβ25-35 ,respectively for 48 h, and their absorbance (A) value by MTT conversion was compared among three groups.ResultsCell clone highly expressing GPX1 stably were obtained by G418 selection. The increment of cell inhibition ratio was 24.7 ％ after 20 μmol/L Aβ25-35 treatment for 48 h, compared with control group (P＜0.01). Thus the optimization concentration of Aβ25-35 was 20 μmol/L. After treatment with 20 μmol/L for 48 h, the A value was significantly higher in GPX1/pLNCX/PC12 group than in pLNCX/ PC12 group and in PC12 cells group(0.53±0. 02 vs. 0.44±0.02;0.53±0.02 vs. 0.39±0.07, P＜0.01). Conclusions Transfection of GPX1 recombinant plasmid may protect cell against injury from free radical and reverse the decrease of PC12 cell survival rate impaired by Aβ25-35.

Expression of GPX1-mRNA and apoptosis related signal molecular in Keshan disease patients / 中国地方病学杂志

Objective To investigate the meaning of expression of apoptosis related molecules NFKBp65 and p53 and GPX1-mRNA in patients with Keshan disease(KSD).Methods Sixteen chronic Keshan Disease patients were enrolled in KSD group according to electrocardiogram,chest X ray film and clinical examinations on 15,September in 2009,and 23 healthy people were included in control group from physical examination taken in The Second Affiliated Hospital of Xi'an Jiaotong University.Fresh blood(5 ml)was collected from antecubital vein of all subjects in the fasting state.Total mRNA and protein of blood sample were isolated using Trizol.GPX Assay Kit was used to detect GPX enzyme activity,and GPX1-mRNA expression was determined by SYBR Real-Time PCR.Meanwhile,expression of apoptosis related molecules NFKBp65 and p53 were determined by Western blot.Results GPX enzyme activity decreased significantly in KSD group[(108.61±14.10)U]compared with control group[(122.78±11.89)U,t=2.874,P<0.05],GPX1-mRNA level of KSD group(0.553±0.299)notably KSD group(0.802±0.057)compared with control group[(1.065±0.355),t=6.829,P<0.01].p53 increased in KSD group(1.604±0.191)compared with control group[(1.137±0.186),t=3.033,P<0.05].Conclusiom Decreased GPX1-mRNA expression may result in lower GPX enzyme activity of patients with KSD.Thus oxidative damage increases and cadioeyte apoptosis is activated by activating apoptosis signal pathway.

Effects of angle and accumulative irradiation on ability of antioxidation and the antioxidase activity on rats / 中华放射医学与防护杂志

Objective To compare the changes in nitric oxide (NO), total ability of anti-oxidize antioxidase, superoxide dismutase (SOD), glutathion peroxidase (GSH-PX), catalase (CAT) and maleic dialdehyde(MDA) in rats after single and accumulative 60Co γ-irradiation . Methods 48 rats were randomly divided into two groups of single and accumulative irradiation. Each group was irradiated by 60Co gamma-rays. The total irradiation doses were 0.4, 0.8, 1.6, 3.2 and 6.4 Gy, respectively in each group. The NO, total ability of anti-oxidize antioxidaze, SOD, GSH-PX, CAT and MDA in serum were measured at day 1 after last irradiation. Results Compared with the single irradiation group, the NO (52.6-117.9 μmol/ml), total ability of anti-oxidize antioxidaze (3.3-26.2 U/ml), the antioxidase activity of the SOD (26.3-167.5 U/ml), GSH-PX (740.8-2462.4 U/ml), CAT (3.3-29.4 U/ml) and the content of MDA(29.3-155.1 nmol/ml) of mt serum in accumulative irradiation group were increased after irradiation, which was related with the accumulative irradiation dose. For instance, total ability of anti-oxidize antioxidase (26.2 U/ml), antioxidase activity of the SOD (167.5 U/ml) and CAT (29.4 U/ml) in 0.4 Gy group of accumulative irradiation were significandy increased when compared with those of control group. However, the content of MDA in accumulative irradiation group was obviously higher than that in single radiation group when the irradiation doses delivered over 3.2 Gy, which might be correlated with higher antioxidase activity. Conclusions Low dose of accumulative gamma-rays irradiation can induce the stimulative effect of antioxidase activity. However, higher dose of accumulative gamma-rays irradiation can damage the activity of antioxidase.

Cambios en el sistema de defensa antioxidante inducido por Ciclosporina A / Changes in the antioxidant defence system induced by Cyclosporin A

La Ciclosporina A (CyA) es un inmunosupresor que presenta efectos adversos como la hepatotoxicidad. Se estudió el efecto de CyA sobre el sistema de defensa antioxidante (SDA), su relación con la lipoperoxidación y la función hepática. Ratas machos wistar de 200-260 g de peso fueron tratadas durante 7 días (agudo) y 120 días (crónico) con dosis orales de CyA de 5 y 20 mg/kg/ día. Se estudió el SDA midiendo el contenido hepático total de glutatión (GSH), glutatión peroxidasa (GPx) y catalasa (CAT); el perfil de funcionamiento hepático (PFH) se realizó determinando aspartato aminotransferasa (AST), alanín aminotransferasa (ALT) y bilirrubina total (Bt) y para la lipoperoxidación se midieron las sustancias reactivas al ácido tiobarbitúrico (SRAT). Los resultados fueron confirmados con estudios histológicos. El tratamiento agudo con 20 mg/kg/día de CyA mostró aumento significativo de SRAT (30,51±1,97 nmol/g), pérdida de GSH (2,47±0,06 µmol/g), incremento significativo de GPx (663,25±1,88 mU/mg) y CAT (290,65±3,31 mU/mg). El tratamiento crónico con 5 mg/kg/día de CyA mostró disminución tiempo-dependiente del SDA con disminución de GSH (3,19±0,05 µmol/g), GPx (569,6±2,67 mU/mg) y CAT (223,3±2,78 mU/mg), sin cambios en SRAT. Los resultados del tratamiento crónico y agudo con 20 mg/kg/día de CyA son coincidentes y sólo en esta dosis se observaron alteraciones de la histo-arquitectura del parénquima hepático. Se concluye que dosis de 20 mg/kg/día de CyA en tratamiento agudo y crónico provocan lipoperoxidación con compromiso del SDA y alteración del hepatocito; dosis de 5 mg/kg/día de CyA en tratamiento crónico producen deterioro reversible del SDA sin lipoperoxidación. La inmunosupresión aplicada en clínica con dosis de 3 a 8 mg/kg/día produciría disminución del SDA sin cambios en la histo-arquitectura del parénquima hepático.

Cyclosporin A (CyA), an immunosuppressive agent, exerts adverse effects such as hepatotoxicity. The effect of CyA on the Antioxidant Defence System(ADS), its relation to lipoperoxidation, and liver function were studied. Assays were performed on male wistar rats weighing 200-260 g during acute (7 days) and chronic (120 days) treatment with oral doses of CyA of 5 and 20 mg/kg/day. ADS was studied in rat liver homogenate by measuring the liver content of total glutathion (GSH), glutathion peroxidase(GPx) and catalase (CAT); the Liver Profile Test (LPT) was measured by determining aspartate amino transferase (AST), alanin amino transferase (ALT) and total bilirubin (TB), and lipoperoxidation by determining thiobarbituric acid reactive substances (TRAS). The results were confirmed by histological studies. In the acute treatment, 20 mg/kg/day with CyA, a significant increase in TRAS (30.51±1.97 nmol/g), a loss of GSH (2.47±0.06 µmol/g) and a significant increase in GPx (663.25±1.88 mU/mg) and CAT (290.65±3.31 mU/mg) were observed. In the chronic treatment, 5 mg/kg/day with CyA, a time-dependent decrease in the ADS with a diminution in GSH (3.19±0.05 µmol/g), GPx (569.6±2.67 mU/mg) and CAT (223.3±2.78 mU/mg) were observed, with no changes in TRAS. The results for the chronic and acute treatment with 20 mg/kg/day of CyA are coincident, only this dose causing alterations in liver parenchyma histoarchitecture. CyA doses of 20 mg/kg/day during acute and chronic treatment cause lipoperoxidation with ADS involvement and hepatocyte alteration. CyA doses of 5 mg/kg/day during chronic treatment cause deterioration in the ADS with no lipoperoxidation, hepatotoxicity being reversible. Immunosuppression in human patients with 3 to 8 mg/kg/day doses, would cause a decrease in the ADS with no structural or functional changes in the hepatocyte.

Effect of Air Pollution on Serum Oxidative Stress Indices in Traffic Policemen / 环境与健康杂志

Objective To explore the effect of air pollution on oxidative stress indices(SOD,GSH-Px,MDA) in serum of traffic policemen. Methods From Jun to Aug,2007,sixty-two traffic policemen and thirty-five male suburban inhabitants were selected. The ambient concentrations of PM2.5,polycyclic aromatic hydrocarbons(PAHs) ,nitrogen dioxide,formaldehyde,benzene and toluene were monitored within two consecutive days in the work places of traffic policemen and in the residential areas of suburban inhabitants to assess their air pollution exposure levels. The activity of SOD,GSH-Px and the concentration of MDA in serum were determined with regent kits,while the information on smoking,drinking alcohol,exercising habit and so on was investigated by questionnaire. Results There were significant differences in the concentrations of nitrogen dioxide,formaldehyde,benzene and toluene between the two study groups. The average levels of PM2.5 and PAHs in the traffic policeman group were also higher than those in the control group,but this difference was not significant for small sample size. The activities of SOD and GSH-Px in the traffic policeman group were significantly higher than those in the control group,while the difference of MDA concentration between the two groups was not significant. The relationship between air pollution and the activity of SOD and GSH-Px were also significant after controlling the influence of other factors. Conclusion Air pollution can decrease the activity of SOD and GSH-Px in serum of traffic policemen and induce oxidative stress.

Effect of interaction between smoking,alcohol drinking and polymorphisms of phase Ⅱ metabolic genes on the susceptibility of hepatocellular carcinoma / 基础医学与临床

Objective This study intended to explore the relationship of the polymorphisms of phase Ⅱ metabolic genes (GSTM1 and EPHX1), smoking, alcohol drinking and their interactions on risk of hepatocellular carcinoma(HCC). Methods Using multiplex PCR and PCR-RFLP, the genotypes of GSTM1 and EPHX1 were analyzed in 105 patients with HCC and 151 health controls in Guangxi. The state of smoking and alcohol drinking were investigated. Results The frequency of the GSTM1 null genotype in cases was 64.76% and 50.99% in controls, which was significantly different(P

The levels of intraeythrocytic glutathion and its related factors in IGT and newly diagnosed type 2 diabetes patients / 医学研究生学报

Objective:To evaluate the antioxidant status in IGT and newly diagnosed type 2 diabetes patients, we detected the levels of serum Vitamin E(Vit E), vitamin C(Vit C) and intraerythrocytic glutathion(GSH).Methods:The levels of serum Vit E, Vit C and intraerythrocytic GSH were measured in 32 IGT and 41 newly diagnosed type 2 diabetes patients, and the associated factors with GSH/GSSG (oxidized glutathione) were evaluated.Results:Significant decrease of serum Vit C intraerythrocytic GSH and GSH/GSSG were noted in IGT and newly diagnosed type 2 diabetes patients. There were negative correlation between GSH/GSSG and blood glucose, triglyceride, HbA_(1c) in IGT and newly diagnosed type 2 diabetes patients.Conclusion:The results showed that antioxidant defenses are decreased in IGT and newly diagnosed type 2 diabetes patients. To improve the metabolism of blood glucose and triglyceride may have some beneficial effects on antioxidant defenses in IGT and newly diagnosed type 2 diabetes patients.

The Change of Glutathione Content in the Placenta of Patients with Pregnancy-induced Hypertension / 대한산부인과학회잡지

Glutathione has a key role in several detoxification reactions and in the protection against injury caused by reactive oxygens. Pregnancy-induced hypertension(PIH) is associated with endothelial cell dysfunction. Such dysfunction could be caused by oxidative stress. There is evidence of increased activity of free radicals in PIH, but little is known about the part played by changes in specific antioxidants. In this study, the changes of glutathione levels were investigated in blood of patients with PIH, and cord blood of these patients was also investigated. The glutathione levels in cord blood of neonates from hypertensive pregnant women were significantly higher than in cord blood from normotensive pregnant women. The changes of gamma-glutamuylcysteine synthetase and of glutathione s-transferase in placenta were not significant, but gamma-glutamyl transpeptidase activity increased significantly in placenta of hypertensive pregnant women. These results suggest that the increased glutathione in cord blood of patients with PIH may be due to increased glutathione interorgan transport resulting from incerased activity of the placenta gamma-glutamyl transpeptidase.

Effect of Exogenous Adrenomedullin on the Glutathion Levels of Plasma and Brain Tissue in Neonatal Rat with Hypoxic-Ischemia Reperfusion Brain Damage / 实用儿科临床杂志

Objective To explore the effect of exogenous adrenomedullin(ADM) on expressions of glutathion in plasma and brain tissue inneonatal rats with hypoxic-ischemia reperfusion brain damage(HIRBD) and the mechanism of action.Methods Fifty-six cases of 7 d SD rats were randomly divided into 4 groups including normal control group(without any treatment),HIRBD group(the model with hypoxia for 2 h and ischemia for 1 h),primed group(abdomen infusion of ADM at 0.5 h before making model,the other was same to the HIRBD group)and treatment group(abdomen infusion of ADM at onces after making model,the other was same to the HIRBD group).The neonatal rats in 4 groups were derived blood and brain tissue after decapitation at either 4 h or 24 h after reperfusion.The levels of gtutathion(GSH) in plasma and brain tissue were determined by using chromatometry.Results In HIRBD group,the affection areas at 24 h after reperfusion enlarged compared with those at 4 h after reperfusion.Meanwhile,the affection of punctiform degeneration or necrosis at 4 h after reperfusion transformed into the affection of lamellar or diffuse degeneration or necrosis at 24 h after reperfusion.The levels of GSH in plasma and brain tissue in HIRBD group at either 4 h or 24 h after reperfusion were significantly lower than that in normal control group(Pa0.05).Meanwhile the pathology score of brain section in primed group and treatment group were significantly lower than that in HIRBD group at either 4 h or 24 h after reperfusion(Pa0.05).Conclusion Exogenous ADM can induce the neuroprotection in HIRBD by adjusting the expression of GSH.

?-Glutamyl transpeptidase activity and GSH content in benign hyperplastic prostatic tissue and stroma and epithelial cells / 中国病理生理杂志

?-GT activity and its substrate GSH content in tissue homogenate, epithe-lium and stroma of normal and benign hyperplastic human prostates were measured tostudy their relationship with pathogenesis of benign prostatic hyperplasia (BPH). Theresults were: a) ?-GT activity in BPH tissues were very much increased; but GSHcontent was much decreased; b) The ?-GT activity in epithelium of both normal andBPH were much higher than that in relative stroma. However epithelium GSH contentwere lower than that of stroma. Thase results suggested that increand ?-GT activity anddecreased GSH content play an important role in pathogenesis of BPH.