胡黄连甙II和神经生长因子对H_2O_2损伤的PC12细胞的协同保护作用(英文)

目的:考察胡黄连甙II和NGF对双氧水损伤细胞的协同保护作用。方法:以CDCFH方法评价活性氧水平,MTT方法、细胞形态观察以及LDH漏出实验评价药物对细胞损伤的修复作用。结果:25μg/mL胡黄连甙II和2 ng/mL NGF显著改善H2O2诱导的PC12细胞损伤,同时有效降低细胞内ROS。细胞形态改善、细胞活力提高、ROS清除作用均表明胡黄连甙II和NGF协同保护氧化应激对神经细胞的损伤。结论:胡黄连甙II和NGF的协同作用能有效治疗神经性疾病。     

Synergistic protective effect of picroside II and NGF on PC12 cells against oxidative stress induced by H2O2

Epidemiological studies suggest that nerve growth factor (NGF) is associated with a reduced risk of acute or chronic neuropathies. We studied the synergistic protective effect of picroside II and NGF against the oxidative stress in PC12 cells induced by hydrogen peroxide (H2O2). The fluorescent probe CDCFH was used to assess the intracellular reactive oxygen species (ROS) level, and MTT assay, morphological observation as well as LDH leakage test were conducted to measure cellular injury. The H2O2-induced cytotoxicity was significantly attenuated in the presence of picroside II (25 microg/ml ) and NGF (2 ng/ml). Cultures with this combined treatment possessed decreased level of ROS while increased cell survival, as compared to that of picroside II or NGF alone-treated cells. Accordingly, it was concluded that their synergistic protective activities against oxidative stress in vitro were demonstrated in various aspects, including reversing morphological changes, enhancing the ability of cell proliferation and ROS scavenging. Such action supports the therapeutic potential of picroside II and NGF in treating nervous disorders based on their synergistic effect.     

胡黄连甙Ⅱ和神经生长因子对H2O2损伤的PC12细胞的协同保护作用

目的:考察胡黄连甙II和NGF对双氧水损伤细胞的协同保护作用.方法:以CDCFH方法评价活性氧水平,MTT方法、细胞形态观察以及LDH漏出实验评价药物对细胞损伤的修复作用.结果:25 μg/mL胡黄连甙II和2 ng/mL NGF显著改善H2O2诱导的PC12细胞损伤,同时有效降低细胞内ROS.细胞形态改善、细胞活力提高、ROS清除作用均表明胡黄连甙II和NGF协同保护氧化应激对神经细胞的损伤.结论:胡黄连甙II和NGF的协同作用能有效治疗神经性疾病.     

依达拉奉对硝普钠诱导PC12细胞氧化应激的保护作用

目的研究依达拉奉对硝普钠诱导PC12细胞损伤的保护作用,并探讨其作用机制。方法以500μmol.L-1硝普钠诱导PC12细胞氧化应激损伤,MTT法测定细胞存活率,倒置显微镜观察细胞形态,流式细胞仪检测细胞凋亡,蛋白免疫印迹检测Bax和Bcl-2表达变化。结果依达拉奉在25μmol.L-1能增加氧化应激损伤细胞活力,在75μmol.L-1其保护作用达到峰值,能明显改善细胞形态结构,减少早期凋亡细胞数目,升高细胞Bcl-2/Bax比值。结论依达拉奉对硝普钠诱导的PC12细胞损伤具有保护作用,其机制可能与依达拉奉清除NO,抑制线粒体凋亡通路有关。     

Digitoflavone provokes mitochondrial biogenesis in PC12 cells: A protective approach to oxidative stress

Abstract

Context: Reactive oxygen species (ROS) are known to be one of the main causes of neurodegenerative disorders, and flavonoids play characteristic roles in a variety of biological activities, and specially are known to be antioxidant reagents.

Objective: In this study, we investigated neuroprotective effects of digitoflavone to suppress H₂O₂ -induced cell death in neuron-like PC12 cells.

Material and methods: PC12 cells were pre-treated with digitoflavone for 2?h and then cells were exposed to H₂O₂ for 18?h. The cells’ viability was evaluated by MTT assay. Rhodamine 123 staining was used for the determination of mitochondrial membrane potential (ΔΨ_m). The intracellular ROS aggregation was determined by using 2′,7′-dichlorofluorescein diacetate. Also, the level of mitochondrial biogenesis factors was measured by western blot. The antioxidant capacity of digitoflavone was also determined by measuring reduced glutathione (GSH) level and catalase (CAT) activity quantification.

Results: Digitoflavone significantly elevated cells’ viability at concentrations of 10 and 20?µM. Also, digitoflavone attenuated intracellular level of ROS, and stabilized ΔΨ_m. Moreover, digitoflavone increased phosphorylation of AMP-activated protein kinase (AMPK) and, consequently, elevated mitochondrial biogenesis factors which were reduced after H₂O₂ exposure. We emphasized on the protective effect of digitoflavone through increasing mitochondrial biogenesis by specifically inhibiting AMPK. Antioxidant ability of digitoflavone was indicated by the elevation of GSH level and CAT activity.

Conclusion: As a result, digitoflavone stabilize ΔΨ_m, enhanced cell viability through inducing mitochondrial biogenesis pathway, and increased antioxidant capacity of the cells which lead to better combating the oxidative stress.     

Antioxidant activity and protective effects of peptide lunasin against oxidative stress in intestinal Caco-2 cells

Oxidative stress is one of the most critical factors implicated in many disorders of the gastrointestinal tract, such as inflammatory bowel diseases and colon cancer. Lunasin is a seed peptide known by its properties against cancer and cardiovascular diseases. The present study investigated the in vitro antioxidant activity of this peptide that demonstrated to be a potent scavenger of peroxyl and superoxide radicals. In addition, the protective role of lunasin on cell viability and antioxidant defenses of human Caco-2 cells challenged by hydrogen peroxide and tert-butylhydroperoxide was evaluated. This peptide remained partially intact during incubation time with cells, preventing of the oxidative damage induced by both chemical agents. The direct antioxidant action of lunasin (within the physiological range of concentrations) on enterocytes exposed to oxidizing species makes this peptide a promising agent to preserve the integrity of intestinal mucosa against oxidative damage related diseases.     

Antioxidant,free radical scavenging activities of Salvia brachyantha and its protective effect against oxidative cardiac cell injury

In this study, antioxidant and free radical scavenging activities of an endemic Salvia species (Salvia brachyantha (Bordz) probed. was assessed in vitro using 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, β-carotene linoleic acid, superoxide anion radical, hydroxyl radical, and reducing power assays. Regarding our data, the plant extract exhibited antioxidant and radical scavenging activities at different magnitudes of potency. In addition, this study was undertaken to assess whether methanol extract of S. brachyantha could increase the endogenous antioxidant enzymes in cells, and where such increased cellular defences could provide protection against oxidative cell injury. Pre treatment of rat heart cell lines with 100 μg/ml of plant extract for 24 h significantly prevented cell damage and enhanced activity of antioxidant enzymes induced by a treatment with xanthine/xanthine oxidase. Increased reactive oxygen species and cell apoptosis induced by xanthine/xanthine oxidase was dose-dependently prevented when cells were pre treated for 24 h with plant extract. These results indicated that S. brachyantha could protect against cell injury via induction of the antioxidant enzyme defences. The extract of this plant might be valuable antioxidant natural sources and seemed to be applicable in both healthy medicine and food industry.     

Antioxidant properties of Ferulago angulata and its hepatoprotective effect against N-nitrosodimethylamine-induced oxidative stress in rats

Context: Ferulago angulata (Schlecht.) Boiss. (Apiaceae) (FASB) is used to treat liver diseases and has been used both as food and therapeutics by many cultures for thousands of years because of the natural antioxidant compounds.

Objective: This study determines antioxidant properties of FASB flowers, the levels of minerals and vitamins, and also, evaluates the hepatoprotective effect of flowers against N-nitrosodimethylamine (NDMA) induced on liver tissue by assessing antioxidant enzymes and histopathological parameters in Wistar albino rats.

Materials and methods: In the study, the rats were divided into six groups of ten. Control, untreated animals were given 0.9% NaCl. Rats were intraperitoneally given NDMA (10?mg/kg) for the first 7 days. FASB methanol extract (150 and 300?mg/kg) was administered orally for 21 days.

Results: α-Tocopherol, retinol, ascorbic acid, total antioxidant activity, phenolic and flavonoid contents of FASB were 0.70?±?0.13, 0.29?±?0.03?μg/g, 139.32?±?7.06?μg/100?g, 171.61?±?6.05?mM ascorbic acid/g, 90.47?±?4.11?mg GA/g and 37.39?±?2.85?mg QE/g. DPPH and hydroxyl radical scavenging activity was obtained IC₅₀ 67.34?±?4.14 and 64.87?±?4.68?μg/mL, respectively.

Discussion and conclusion: The results of the study indicated that FASB flowers contain high levels of vitamins, minerals, total antioxidant activity, phenolics and flavonoids. Due to the positive effect on significant changes in antioxidant enzymes of liver tissue and histopathological examination, it is thought that the plant could be used as a hepatoprotective.     

一氧化氮诱导PC12细胞凋亡及芍药苷的保护作用

目的:探讨一氧化氮诱导PC12细胞凋亡及芍药苷保护作用的可能机制.方法:MTT和乳酸脱氢酶活性测定细胞存活率,DNA凝胶电泳观察DNA的断裂情况,流式细胞仪测定细胞凋亡率、检测线粒体跨膜电位.结果:500 μmol·L-1 硝普钠(SNP)可诱导PC12细胞凋亡,细胞线粒体跨膜电位明显下降.预先经过 0.1、1和10 μmol·L-1 等浓度芍药苷处理后, SNP诱导的PC12细胞凋亡明显减少,同时明显减弱一氧化氮对线粒体跨膜电位的影响.结论:芍药苷可抑制一氧化氮诱导PC12细胞凋亡,其作用机制可能与其稳定细胞线粒体跨膜电位有关.     

槲皮素对大剂量X线暴露所致PC12细胞氧化性损伤的保护作用

目的探讨槲皮素对PC12细胞的毒性及其对大剂量X线诱导PC12细胞氧化性损伤的保护作用。方法槲皮素6.25,12.5,25,50和100μmol·L-1分别作用于PC12细胞,于24,48和72 h后采用MTT法检测PC12细胞增殖。槲皮素12.5,25和50μmol·L-1分别与PC12细胞预孵育2 h,随后采用4 GyX线辐照PC12细胞,于24 h后,采用MTT法检测PC12细胞增殖反应,黄嘌呤氧化酶法检测细胞内超氧化物歧化酶(SOD)活性,硫代巴比妥法检测丙二醛(MDA)含量,菲啉络合法检测总抗氧化能力(T-AOC),DCFH-DA探针法检测活性氧(ROS)含量。结果槲皮素6.25～100μmol·L-1与PC12细胞作用24 h(r=0.887,P<0.01)和48 h(r=0.872,P<0.01)具有促细胞增殖作用,作用72 h表现出明显的细胞毒性,且随浓度增加毒性增大(r=0.942,P<0.01)。与正常对照组比较,PC12细胞受辐射后细胞增殖反应、SOD活性和T-AOC降低(P<0.01),MDA和ROS含量增加(P<0.01)。与辐照对照组比较,槲皮素12.5,25和50μmol·L-1防护组PC12细胞增殖反应(r=0.751,P<0.01),SOD活性(r=0.837,P<0.01)和T-AOC(r=0.940,P<0.01)随槲皮素浓度增大而增高,MDA含量(r=0.845,P<0.01)和ROS含量(r=0.930,P<0.01)随槲皮素浓度的增高而降低。结论槲皮素对大剂量X线诱导PC12细胞氧化性损伤具有一定的防护作用,在12.5～50μmol·L-1浓度范围内其防辐射作用与浓度呈较好的相关性。     

Antioxidant enzyme activities and oxidative stress in affective disorders

Recent data from several reports indicate that free radicals are involved in the biochemical mechanisms underlying neuropsychiatric disorders in human. The results of several reports suggest that lower antioxidant defences against lipid peroxidation exist in patients with depression and that there is a therapeutic benefit from antioxidant supplementation in unstable manic-depressive patients. We investigated the antioxidant enzyme status and the indices of oxidative stress and lipid peroxidation end products in erythrocytes from patients with affective disorder. For this purpose, we measured superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, as well as malondialdehyde (MDA) and nitric oxide (NO) levels in patients with affective disorders (n=30) in both pre- and post-treatment periods, and in a control group (n=21). CAT activities were significantly decreased in both pre-, and post-treatment periods in patients compared to the control group. GSH-Px activity in the pre-treatment period in the patients was significantly lower than both post-treatment patient and control groups. MDA levels were increased in both pre-, and post-treatment patient groups compared to the control group. NO level was lower in the pre-treatment patient group than in the control group. There were statistically significant correlations between SOD and MDA, and SOD and NO in the pre-treatment patient and control groups. Because the overall study sample was small, and the post-treatment patient group was even smaller, it can tentatively be suggested that the antioxidant system is impaired during a mood episode in patients with affective disorders, normalizing at the end of the episode.     

Nuclear factor-kappaB mediates cytoprotection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells

1. Cytoprotection by H(2)O(2) preconditioning against oxidative stress-induced apoptosis of PC12 cells has been demonstrated previously. In the present study, we investigated the effects of H(2)O(2) preconditioning on nuclear factor (NF)-kappaB activation and the role of NF-kappaB in the adaptive cytoprotection of H(2)O(2) preconditioning in PC12 cells. 2. The PC12 cells were preconditioned with 100 micromol/L H(2)O(2) for 90 min, followed by 24 h recovery and subsequent exposure to 300 micromol/L H(2)O(2) for a further 12 h. 3. The results showed that preconditioning with 100 micromol/L H(2)O(2) upregulated NF-kappaB expression and enhanced its nuclear translocation and DNA binding activity. In addition to its own effects on NF-kappaB expression, H(2)O(2) preconditioning also promoted the overexpression of NF-kappaB induced by a lethal concentration of H(2)O(2) (300 micromol/L). 4. N-Tosyl-l-phenylalanine chloromethyl ketone (TPCK; 20 micromol/L), an inhibitor of NF-kappaB, was administered 20 min before preconditioning with 100 micromol/L H(2)O(2). At this concenteration, TPCK blocked the overexpression of NF-kappaB induced by H(2)O(2) preconditioning, accompanied by attenuation of H(2)O(2) preconditioning-induced cytoprotection. The inhibition of NF-kappaB by TPCK enhanced caspase 3 activity induced by 300 micromol/L H(2)O(2). 5. The findings of the present study provide novel evidence for the effects of preconditioning with H(2)O(2) on constitutive activation of NF-kappaB, which contributes to the adaptive cytoprotection of H(2)O(2) preconditioning against PC12 cells apoptosis.     

咖啡酸对氧化应激诱导的PC12细胞5-脂氧酶激活的抑制作用

目的探讨咖啡酸是否通过抑制氧化应激诱导的5-脂氧酶(5-LOX)激活而减轻细胞损伤。方法稳定转染绿荧光蛋白(GFP)-5-LOX的PC12细胞,预先给予咖啡酸0.001~10μmol.L-1和对照药MK886,30min后观察缺氧缺糖/恢复(OGD/R)及过氧化氢(H2O2)160μmol.L-1处理后的变化。MTT法和碘化丙啶染色法分析细胞存活率和死亡率;荧光显微镜观察OGD 2 h/R2 h和H2O2处理40 min时5-LOX的核膜移位;ELISA法测定OGD 2 h/R 3 h时5-LOX代谢产物的生成;DCF法检测OGD 2 h/R 0.5 h细胞内活性氧(ROS)的产生。结果 OGD 2 h/R 24 h GFP-5-LOX转染和GFP-转染PC12细胞的存活率分别为(63.1±6.6)%和(70.7±6.9)%;H2O2处理24 h细胞存活率分别为(62.5±7.7)%和(75.7±9.5)%。在GFP-5-LOX转染的PC12细胞中,咖啡酸和对照药MK886可使OGD/R细胞存活率从(63.1±6.6)%分别增加到(87.3±2.0)%和(89.9±6.3)%,细胞坏死率从(31.4±1.5)%降低到(10.1±2.0)%和(11.7±1.3)%(P<0.01);使H2O2处理细胞存活率从(62.51±7.65)%增加到(92.59±4.02)%和(75.31±6.60)%;使OGD/R细胞CysLTs的生成从261.1±33.7降低到108.5±16.7和(90.6±19.5)ng.g-1蛋白(P<0.01)。此外,咖啡酸抑制OGD/R诱导PC12细胞的ROS产生,IC50值为8.021μmol.L-1;抑制OGD/R诱导的GFP-5-LOX转染的PC12细胞5-LOX核膜移位,IC50值为0.974μmol.L-1;抑制H2O2诱导的GFP-5-LOX转染的PC12细胞5-LOX核膜移位,IC50值为0.501μmol.L-1;MK886无上述作用。结论咖啡酸可抑制氧化应激诱导的PC12细胞5-LOX激活,对缺血损伤的PC12细胞具有保护作用。     

Resveratrol oligomers from Vitis amurensis attenuate beta-amyloid-induced oxidative stress in PC12 cells

Oxidative damage induced by beta-amyloid (Abeta) is closely associated with the hallmark pathologies of Alzheimer's disease (AD) and may play a critical role in the development of AD. In this study, the protective effects of vitisin A and heyneanol A, resveratrol oligomers isolated from Vitis amurensis Rupr. (Vitaceae), against Abeta-induced oxidative cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta (20 microM) for 24 h resulted in neuronal cell death, whereas pretreatment with vitisin A or heyneanol A at the concentration range of 5-50 microM reduced Abeta-induced cell death. In addition, Abeta-induced elevation of reactive oxygen species generation, the primary cause of Abeta-induced oxidative stress, was attenuated by treatment of vitisin A or heyneanol A (10, 25, 50 microM). Abeta-treated cells also displayed characteristic features of apoptosis such as induction of DNA fragmentation and caspase-3 activation, but vitisin A and heyneanol A (10, 50 microM) significantly suppressed these events. These results suggest that vitisin A and heyneanol A prevent Abeta-induced neurotoxicity through attenuating oxidative stress induced by Abeta, and may be useful as potential preventive or therapeutic agents for AD.     

氧化应激致PC12细胞凋亡的信号传导途径的研究进展

PC12细胞被广泛用于神经细胞功能、分化、凋亡和神经递质分泌,以及潜在的分子机制的研究。氧化应激可导致PC12细胞凋亡,其作用方式为激活对氧化还原反应敏感的细胞信号传导,主要与丝裂原活化蛋白激酶、线粒体凋亡及NF-κB信号传导途径有关。本文综述了氧化应激致PC12细胞凋亡的信号传导途径,旨在为神经系统氧化应激相关疾病的抗氧化剂药物治疗和凋亡信号途径药物干预治疗提供理论依据。     

The protective effect of taurine against cyclosporine A-induced oxidative stress and hepatotoxicity in rats

Cyclosporine A (CsA) is the immunosuppressor which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been implicated as one of the possible mechanisms of CsA-induced hepatotoxicity. The present investigation examined the ability of taurine as an antioxidant to protect against CsA-induced oxidative stress and hepatotoxicity. CsA hepatotoxicity was induced by subcutaneous injection of CsA at a dose of 20mg/kg body weight daily for 21 days. Hepatotoxicity was assessed by reduced serum total protein level and increased serum levels of gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransaminase (AST). CsA treatment increased lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) concentration and decreased reduced glutathione (GSH) content and activities of catalase and glutathione peroxidase (GSH-Px) in the rat liver. Taurine administration (1% in the drinking water) for 3 days before and concurrently during CsA injections improved liver functions, as indicated by decline of serum transaminases and GGT levels and elevation of serum total protein. Moreover, taurine significantly reduced hepatic TBARS and increased GSH content and catalase and GSH-Px activities in the hepatic tissue. These results indicate that taurine has a protective action against CsA hepatotoxicity and suggest that taurine may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.     

Induction of oxidative stress by endosulfan and protective effect of lipid-soluble antioxidants against endosulfan-induced oxidative damage

The toxic mechanism of endosulfan, a widely used organochlorine pesticide, was investigated in Saccharomyces cerevisiae and human cell lines. A concentration-dependent inhibition of cell growth was observed when S. cerevisiae was exposed to endosulfan, and its cytotoxicity (IC(50)) was found to be 49 microM and 86 microM in HepG2 and HeLa human cell lines, respectively. The treatment of S. cerevisiae with endosulfan resulted in oxidative damage, as demonstrated by thiobarbituric acid-reactive substance (TBARS) production, in a dose-dependent manner, and the growth inhibition was recovered by treatment with lipid-soluble antioxidants, such as alpha-tocopherol or beta-carotene, suggesting that endosulfan toxicity may be closely associated with endosulfan-induced reactive oxygen species (ROS) generation. The inhibition of cellular respiration by endosulfan treatment and the recovery of respiration activity by antioxidant treatment confirmed that endosulfan induces oxidative stress and inhibits respiration via ROS generation. These results suggest that unicellular yeast might provide a useful system for elucidating the toxicity of endosulfan.     

Potential protective effect of melatonin against dibromoacetonitrile-induced oxidative stress in mouse stomach.

Dibromoacetonitrile (DBAN) is a disinfection by-product following chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. DBAN was previously found to induce oxidative stress in rat stomach as manifested by perturbation of some enzymatic and nonenzymatic antioxidant parameters. Therefore, we have investigated the oxidative stress possibly induced by DBAN in mouse stomach and possible protection by melatonin (MLT) as a free radical scavenger. In a dose-response study, mice were administered a single oral dose of DBAN (30, 60 and 120 mg kg(-1)) and were sacrificed after 1 h. DBAN significantly reduced glutathione (GSH) content that was somehow dose-related, and inhibited glutathione-S-transferase (GST) activity in gastric tissues. The highest dose of DBAN (120 mg kg(-1)) lowered GSH by 74% and induced a significant elevation of lipid peroxidation products, determined as thiobarbituric acid reactive substances (TBARS) by 69%. The same dose inhibited the gastric activities of GST, superoxide dismutase (SOD) and catalase (CAT) by 70, 57 and 23%, respectively. In a time-course study, mice were administered DBAN (60 mg kg(-1) p.o.) and sacrificed 0.5, 1, 3, 6, 12 and 24 h after treatment. GSH was dramatically depleted at 0.5, 1, 3 and 6 h (45, 38, 39 and 49% of control, respectively) and remained significantly low at 12 and 24 h. Also, DBAN caused an accumulation of TBARS in gastric tissues starting from 3 h and was maximum at 6 h (133% of the control). The enzymatic activities of GST and SOD were maximally inhibited by DBAN treatment at 0.5 h (32% for GST and 37% for SOD of the respective control). The activities of both enzymes returned to control values at 24 h. CAT activity was not affected by DBAN administration at all. Pretreatment of another group of mice with melatonin (10 mg kg(-1) per day p.o. 12 days) before administration of DBAN (60 mg kg(-1) p.o.) completely mitigated the aforementioned parameters. In conclusion, the present study indicates that DBAN induces a marked oxidative stress in mouse stomach as evidenced by GSH depletion, TBARS accumulation and GST, SOD and CAT inhibition. Melatonin could mitigate DBAN-induced oxidative stress in mouse stomach as it did almost normalize both the enzymatic and nonenzymatic antioxidant parameters.     

Neuroprotective effects of adenosine isolated from Cordyceps cicadae against oxidative and ER stress damages induced by glutamate in PC12 cells

Glutamate has been proven to induce oxidative stress through the formation of reactive oxygen species (ROS) and increased calcium overload which results in neuronal injury, development of neurodegenerative diseases and death. Adenosine is one of the bioactive nucleosides found in Cordyceps cicadae and it has displayed several pharmacological activities including neuroprotection. In this study, the protective effects of adenosine from C. cicadae against glutamate-induce oxidative stress in PC12 cells were evaluated. The exposure of PC12 cells to glutamate (5 mM) induced the formation of ROS, increased Ca²⁺ influx, endoplasmic reticulum (ER) stress and up regulated the expression of pro-apoptotic factor Bax. However, pretreatment with adenosine markedly increased cell viability, decreased the elevated levels of ROS and Ca²⁺ induced by glutamate. Furthermore adenosine increased the activities of GSH-Px and SOD, as well as retained mitochondria membrane potential (MMP), increased Bcl-2/Bax ratio, and reduced the expression of ERK, p38, and JNK. Overall, our results suggest that adenosine may be a promising potential therapeutic agent for the prevention and treatment of neurodegenerative disorders.