Protective Effect of Reduced Glutathione C_(60) Derivative against Hydrogen Peroxide-induced Apoptosis in HEK 293T Cells

Hydrogen peroxide（H_2O_2） and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene（C_（60）） is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione（GSH） is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative（C_（60）-GSH） was successfully synthesized, and its beneficial roles in protecting against H_2O_2-induced oxidative stress and apoptosis in cultured HEK 293 T cells were investigated. Fourier Transform infrared spectroscopy and 1H nuclear magnetic resonance were used to confirm the chemical structure of C_（60）-GSH. Our results demonstrated that C_（60）-GSH prevented the reactive oxygen species（ROS）-mediated cell damage. Additionally, C_（60）-GSH pretreatment significantly attenuated H_2O_2-induced superoxide dismutase（SOD） consumption and malondialdehyde（MDA） elevation. Furthermore, C_（60）-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H_2O_2 stimulation in HEK 293 T cells. Importantly, these protective effects of C_（60）-GSH were superior to those of GSH. In conclusion, these results suggested that C_（60）-GSH has potential to protect against H_2O_2-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.

Changes of Selenium Metabolism Glutathione Peroxidase Activity and Lipid Peroxides Content in Severely Scalding-injured Rats

The changes of sclenium metabolism, glutathione peroxidase activity and lipid peroxidescontent in the tissues of rats suffering from 30% TBSA full thickness scalding were observed in thefirst 7 days after injury. It was found that selenium content in the rat tissues decreased remarkably af-ter injury, which in turn resulted in serious reduction of glutathione peroxidasc activity and significantincrease of lipid peroxides in the scrum, crythrocytcs and liver. However the muscular tissue showedno significant changes. These facts imply that after burn injury, the body is in a state of selenium deficiency, the lossof selenium might be responsible for the reduction of anti - peroxidation ability of glutathioneperoxidase, and conscqucntly there is an increase of lipid peroxides in the tissues. Only the musculartissue is insensitive to lipid peroxidation. It is believed that the reduction of anti-peroxidation abilityof glutathione peroxidasc after bum injury might be one of the main causes to intensify, the injury re-suiting from free radicals.

Flavonoids Reduce Lipid Peroxides and Increase Glutathione Levels in Pooled Human Liver Microsomes (HLMs)

The effects of each of the flavonoids;genistein (G), quercetin (Q) and kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.

Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells

Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antJoxJdant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide ＋ resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage.

Differential generation of hydrogen peroxide upon exposure to zinc and cadmium in the hyperaccumulating plant specie(Sedum alfredii Hance)

Sedum alfredii Hance has been identified as zinc(Zn) and cadmium(Cd) co-hyperaccumulator.In this paper the relationships of Zn or Cd hyperaccumulation to the generation and the role of H2O2 in Sedum alfredii H.were examined.The results show that Zn and Cd contents in the shoots of Sedum alfredii H.treated with 1000 μmol/L Zn2+ and/or 200 μmol/L Cd2+ increased linearly within 15 d.Contents of total S,glutathione(GSH) and H2O2 in shoots also increased within 15 d,and then decreased.Total S and GSH contents in shoots were higher under Cd2+ treatment than under Zn2+ treatment.However,reverse trends of H2O2 content in shoots were obtained,in which much higher H2O2 content was observed in Zn2+-treated shoots than in Cd2+-treated shoots.Similarly,the microscopic imaging of H2O2 accumulation in leaves using H2O2 probe technique showed that much higher H2O2 accumulation was observed in the Zn2+-treated leaf than in the Cd2+-treated one.These results suggest that there are different responses in the generation of H2O2 upon exposure to Zn2+ and Cd2+ for the hyperaccumulator Sedum alfredii H.And this is the first report that the generation of H2O2 may play an important role in Zn hyperaccumulation in the leaves.Our results also imply that GSH may play an important role in the detoxification of dissociated Zn/Cd and the generation of H2O2.

Ascorbate-Glutathione Cycle Alteration in Cadmium Sensitive Rice Mutant cadB-1

A rice cadmium （Cd） sensitive mutant cadB-1 was obtained using Agrobacterium tumefaciens mediated system.After exposure of cadB-1 and wild type （WT） rice seedlings to a range of Cd concentrations for 10 d,Cd accumulated to higher levels in roots,stems and leaves of both cadB-1 and WT with increasing external Cd concentrations,and the inhibition of seedling growth in cadB-1 was more serious than in WT.Hydrogen peroxide accumulation was higher in leaves and roots of cadB-1.The ratios of reduced glutathione （GSH）/oxidized glutathione （GSSG）,ascorbate （ASC）/dehydroascorbate （DHA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH）/oxidized nicotinamide adenine dinucleotide phosphate （NADP＋） were lower in cadB-1 than in WT both in leaves and roots under high Cd levels.The activities of ascorbate peroxidase （APX）,glutathione peroxidase （GR）,dehydroascorbate reductase （DHAR） and monodehydroascorbate reductase （MDHAR） were also lower in cadB-1 than in WT both in leaves and roots under the treatment of high levels of Cd.Our results suggest that under Cd stress,the ASC-GSH cycle was more seriously inhibited in cadB-1 than in WT,indicating that the mutant cadB-1 is less able to scavenge reactive oxygen species and sensitive to Cd.

EFFECTS OF COMBINATION OF ACUPUNCTURE AND MOXIBUSTION WITH CHINESE DRUGS ON LIPIDS PEROXIDE AND ANTIOXIDASE IN PATIENTS OF VASCULAR DEMENTIA

In the present paper, blood lipids peroxide(LPO) level and activities of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) were investigated before and after combined treatment of acupuncture and moxibustion and Chinese drugs in patients of vascular dementia(VD), and their results were compared with those in healthy persons with the similar ages to the patients. The results showed that the blood LPO level increased significantly, and the activities of SOD and GSH-Px reduced significantly in patients of VD as compared with those in the control group. Degrees of patient’s condition were related with amplitudes of the increase of LPO and the reduction of activities of GSHPx and SOD. Combined treatment of acupuncture and moxibustion and Chinese drugs could raise markedly activitles of blood GSH-Px and SOD, and lowered LPO level in the patients of VD, which are related to clinical therapeutic effects. It is considered that combination of acupuncture and moxibustion with Chinese drugs can increase the action of the antiperoxidative system in the patients of VD, exerting anti-peroxidative ability and clearing LPO and reducing the oxidative injury of the organism by oxygen free radical, which is one of mechanisms of combined treatment of acupuncture and moxibustion with Chinese drugs.

Effect of Nicotine on Dopamine and Glutathione Levels in Presence of Oligoelements in Brain Regions of Young Rats——Effect of Nicotine on Brain Regions of Rat

Aim: The purpose of this study was to understand the mechanism of nicotine mediated addiction and the role of oligoelements in reducing its effect. Methods: Male Wistar rats (weight 80 g) were treated with single and repeated doses of nicotine and/or oligoelements as follows: group 1 (control) NaCl 0.9%;group 2, nicotine (1 mg/kg);group 3, oligoelements (50 μl/rat);and group 4, nicotine (1 mg/kg) + oligoelements (50 μl/rat). All drugs were intraperitoneally administered for 4 days. Blood for the measurement of glucose was obtained from all the animals. Samples of the brain regions (cortex, hemispheres and cerebellum + medulla oblongata) of each rat were obtained and used to measure the concentrations of dopamine, GSH levels, and lipid peroxidation (TBARS) using fluorescence and spectrophotometric methods. Results: Glucose level increased in rats treated with nicotine and oligoelements (p < 0.05), while GSH level decreased in cerebellum/medulla oblongata and hemispheres (p < 0.05) of the same animals. TBARS levels increased in cerebellum/medulla oblongata and hemispheres of animals treated with nicotine and oligoelements, but decreased in the same regions (p < 0.05) in rats treated only with oligoelements. The levels of dopamine decreased in cortex and hemispheres, but increased in cerebellum/medulla and oblongata regions of rats treated with both compounds (p < 0.05). Conclusions: Nicotine and oligoelements are associated with increase in the level of glucose, an effect that was more pronounced in the group treated with both drugs. Reduction of oxidative stress and dopamine metabolism may be involved in this effect.

Protection of Salvianolic Acid B for Human Endothelial Cells Against Hydrogen Peroxide-Induced Oxidative Damage

Salvianolic acid B(Sal B) is an active component of traditional Chinese medicine Salvia miltiorrhiza and is used to treat vascular diseases. To better understand its mechanism, the antioxidant capacities of Sal B was evaluated with human endothelial cells under oxidative stress. Human endothelial cells were pretreated with Sal B for 12 h followed by hydrogen peroxide for another 12 h. Production of reactive oxygen species (ROS), activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and concentration of glu-tathione were measured. Protective effect of Sal B on the endothelial cells from hydrogen peroxide-induced damage was observed, and ROS production in the cells was found significantly inhibited. Sal B remarkably enhanced the activities of antioxidant enzymes SOD, CAT and GPX. Furthermore, Sal B up-regulated the intracellular glu-tathione concentration. The results indicate that Sal B protected endothelial cells from oxidative stress by improving the redox status of the cells through enhancing the antioxidant enzyme activities and increasing the reductive glu-tathione concentration after the oxidative challenge.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

硒酵母生理功能研究(Ⅰ)──对小鼠全血GSH-Px,SOD及LPO值的影响

给离乳瑞士种雄性小白鼠饲喂添加硒酵母的饲料，测定小鼠全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）、超氧化物歧化酶（ＳＯＤ）及肝脏过氧化脂质（ＬＰＯ）的含量．结果表明，实验组小鼠全血ＧＳＨ－Ｐｘ活性及ＳＯＤ活性明显地高于对照组。

高血压患者血清SOD、LPO、GSH-PX含量的变化及其临床意义

目的 :探讨了高血压患者血清中SOD、LPO、GSH -PX含量的变化。方法 :分别应用放射免疫分析和生化法对 5 5例高血压患者进行了SOD、LPO、GSH -PX水平的检测 ,并与 38名正常健康人作比较。结果 :高血压患者血清中SOD、GSH -PX水平明显低于正常人组 (P <0 .0 1 ) ,而LPO水平则明显高于正常人组 (P <0 .0 1 )。结论 :血清SOD、LPO、GSH

针刺对光老化大鼠皮肤组织CAT、GSH-Px和H_2O_2影响的实验研究

目的:研究针刺对UV照射引起的皮肤光老化大鼠皮肤组织中过氧化氢酶(CAT)、谷胱甘肽氧化酶(GSH-Px)和过氧化氢(H2O2)的含量的变化,探讨针刺对抗皮肤光老化的作用机理。方法:将大鼠随机分成4组,除正常组外,其余各组模拟日光中UV(UVA+UVB)照射,造成皮肤光老化模型,每次造模前,针刺组给予电针刺激,阳性对照组采用VE涂抹造模部位,15周后对比各组生化指标结果。结果:模型组与正常组比较大鼠皮肤组织中CAT、GSH-Px活性明显降低,H2O2含量明显增加(P<0.05);针刺组与模型组比较CAT、GSH-Px活性增加,H2O2含量明显降低(P<0.05),与VE组比较无统计学意义(P>0.05)。结论:针刺可延缓UV引起的大鼠皮肤光老化,能增强皮肤组织中CAT、GSH-Px活性,降低H2O2含量。

白血病患者化疗前后血清SOD、LPO、GSH-PX水平及其临床意义

目的 :探讨了白血病患者化疗前后血清SOD、LPO、GSH -PX含量的变化。方法 :分别应用放免法和生化法对 4 2例白血病患者进行了化疗前后血清SOD、LPO、GSH -PX含量检测 ,并与 30名正常健康人作对照。结果 :白血病患者化疗前血清SOD、GSH -PX水平明显低于正常组 (p <0 0 1) ,而LPO则明显高于正常 (p <0 0 1) ,化疗后 6个月复发者SOD、LPO、GSH -PX水平持续异常 ,未复发者SOD、LPO、GSH -PX水平接近正常。结论 :观察白血病患者血清SOD、LPO、GSH

还原型谷胱甘肽注射液联合高压氧治疗一氧化碳中毒伴心肌损伤的效果及对心肌损伤的保护作用

目的 研究还原型谷胱甘肽注射液联合高压氧治疗一氧化碳中毒伴心肌损伤的效果及对心肌损伤的保护作用。方法 选取2020年1月—2023年1月收治的一氧化碳中毒伴心肌损伤108例,采用随机数字表法分为观察组和对照组各54例。全部患者实施高压氧治疗,观察组患者则加用还原性谷胱甘肽注射液治疗,2组患者均治疗2周。观察2组患者的治疗效果、血清学指标及心肌指标,以及2组患者不良反应情况。结果 观察组患者治疗总有效率(90.74%,49/54)较对照组(79.53%,41/54)高(P<0.05)。治疗后,2组患者超氧化物歧化酶、谷胱甘肽过氧化物酶水平上升,而脂质过氧化物、丙二醛、肌酸激酶、心肌型肌酸激酶同工酶、天冬氨酸转氨酶、心肌肌钙蛋白T水平下降,且观察组患者上述指标水平改变幅度高于对照组(P<0.05)。治疗后,观察组患者心电图异常率显著低于对照组(P<0.05)。2组患者不良反应比较差异无统计学意义(P>0.05)。结论 还原型谷胱甘肽注射液联合高压氧治疗一氧化碳中毒伴心肌损伤的效果显著,对于心肌细胞损伤具有显著的改善作用。

铁死亡及其在实验性急性肺损伤中的作用

作为一种非凋亡性细胞死亡方式,铁死亡的特征是铁依赖性脂质过氧化物积累引起的膜脂质过氧化、线粒体萎缩等,在形态和生化特性上与其他细胞程序性死亡不同。铁死亡受多种代谢通路调控,参与了失血性休克、缺血再灌注、脓毒症、放射等引起的急性肺损伤。本文综述了铁死亡的主要调控机制及其在多种动物模型急性肺损伤发病机制中的作用,以期为防治急性肺损伤提供新的策略。

铁死亡相关途径改善胃肠道恶性肿瘤细胞耐药性的研究进展

目前,临床上对胃肠道恶性肿瘤的治疗仍然以放化疗为主,但是患者对放化疗药物易产生耐药性,严重影响患者的生活质量。研究发现,肿瘤化疗药物的耐药性是由铁的累积和氧化还原稳态失调所造成,也许调控铁死亡途径可以为胃肠道恶性肿瘤耐药的治疗带来新的机遇。本文对铁死亡的特征、调控机制进行了系统的总结与分析,同时概述了铁死亡不同途径对改善胃肠道恶性肿瘤细胞耐药性的研究进展,旨在为胃肠道恶性肿瘤耐药患者的治疗提供新的思路和方向。

子宫肿瘤患者组织和血清SOD、GSH-Px及LPO含量分析

目的 探讨子宫肿瘤与氧自由基的关系。方法 测定子宫良、恶性肿瘤患者瘤组织、同源瘤旁组织及对照组血清ＳＯＤ、ＧＳＨ－ ＰＸ 和ＬＰＯ 的含量。结果 子宫良性和恶性肿瘤组织中ＳＯＤ、ＧＳＨ－ Ｐｘ／ＬＰＯ 比值均明显低于同源瘤旁组织；恶性肿瘤组织中ＧＳＨ－ Ｐｘ 显著低于瘤旁组织，而ＬＰＯ增高（ Ｐ均＜ ０．００１） ，并且ＧＳＨ－ Ｐｘ／ＬＰＯ比率亦显著低于良性肿瘤组（ Ｐ＜０．００１） ；子宫恶性肿瘤组血清ＧＳＨ－ Ｐｘ／ＬＰＯ 比率明显低于良性肿瘤组和对照组（ Ｐ＜ ０ ．０１） 。结论 机体组织中ＳＯＤ、ＧＳＨ－Ｐｘ 和ＬＰＯ含量变化与子宫肿瘤的发生、发展及恶变密切关联，血清抗氧化酶水平尚不足于恶性肿瘤的早期诊断，但ＧＳＨ－ Ｐｘ／ＬＰＯ比率对子宫肿瘤的良、恶性鉴别具有重要的临床价值。

铁死亡与动脉粥样硬化的联系

铁死亡(Ferroptosis)是新近发现的细胞死亡形式,其特征是细胞内铁离子异常积聚和致死性脂质过氧化。这种调节性细胞死亡与铁代谢、氨基酸代谢、脂质代谢等多种代谢途径有着较为密切的联系。动脉粥样硬化是多种心血管疾病发病的基础之一。近期研究表明,除了凋亡、坏死、自噬等经典死亡途径外,铁死亡也参与了动脉粥样硬化的发生发展。本文阐述了铁死亡机制及其对动脉粥样硬化病变相关细胞及因子的影响。

中药调控成骨细胞铁死亡治疗激素性股骨头坏死

背景:有研究发现成骨细胞铁死亡可作为重要的发病机制诱导激素性股骨头坏死的发生与发展。随着祖国医学的发展,有学者发现某些中药单体、中药复方及中成药等可通过多种通路机制调控成骨细胞铁死亡,最终起到治疗激素性股骨头坏死的作用。目的:探讨成骨细胞铁死亡与激素性股骨头坏死的关系及中草药调控成骨细胞铁死亡治疗激素性股骨头坏死的作用机制,为激素性股骨头坏死的诊治提供新的思路。方法:以“铁死亡,激素性股骨头坏死,成骨细胞,中草药,糖皮质激素,铁代谢,活性氧,谷胱甘肽过氧化物酶”为中文检索词,以“ferroptosis,Hormonal necrosis of the femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,ROS,GPX4”为英文检索词,检索中国知网、Pub Med、万方及维普数据库,筛选各数据库建库至2023年成骨细胞铁死亡与激素性股骨头坏死及中草药干预调控研究相关的文章,最终纳入74篇文献进行综述分析。结果与结论:(1)成骨细胞铁死亡在激素性股骨头坏死发病中起重要作用。(2)成骨细胞铁死亡的发生受到多种机制通路调控,如细胞内铁超载引起铁死亡;细胞发生脂质过氧化损伤细胞膜引起铁死亡;细胞膜上胱氨酸/谷氨酸逆向转运蛋白通过影响谷胱甘肽水平和谷胱甘肽过氧化物酶4活性,从而诱导铁死亡;细胞内发生芬顿反应产生大量活性氧引起铁死亡等。(3)中药单体淫羊藿苷等、中药复方青娥丸等及中成药补肾活血颗粒等均可通过调控成骨细胞铁死亡的发生,有助于防治激素性股骨头坏死。(4)目前关于成骨细胞铁死亡相关机制尚不明确,继续深入探明两者的作用机制,有望为临床治疗激素性股骨头坏死提供新选择。