活性氧在动脉粥样硬化中作用的研究进展

动脉粥样硬化(Atherosclerosis, AS)是心血管疾病的病理基础。活性氧(Reactive oxygen species, ROS)与机体的各种生理过程相关,过高的ROS可以对血管相关的细胞造成损伤,影响其正常功能,并参与AS中血管的损伤和斑块生成。ROS介导的氧化应激参与AS的发生发展,通过调节机体内的抗氧化反应是预防和治疗AS的方向之一,而调节抗氧化相关的转录因子是主要的手段。文章主要从ROS及抗氧化相关转录因子对AS的影响进行综述。     

人参皂苷抗氧化应激损伤作用及其作用机制的研究进展

人参皂苷是一类从人参属药材中提炼出的固醇类化合物。现代药理学研究证实,人参皂苷对中枢神经、心脑血管和免疫系统均有显著的保护作用,可广泛用于相关疾病的治疗。多种疾病可致机体内的氧化与抗氧化系统失衡,导致氧化应激,产生细胞毒性,引起组织损伤。研究表明,有多条信号通路参与氧化应激的过程,主要包括Keap1-Nrf2-ARE,PI3K/AKT,Wnt/β-Catenin和NF-κB等信号通路。随着对人参皂苷研究的深入,多种人参皂苷单体被报道可通过多条氧化应激信号通路发挥抗氧化应激损伤作用。本文综述近年来发表的人参皂苷各活性成分抗氧化应激损伤作用及其相关的作用机制,为人参皂苷的实验研究及临床应用提供理论依据。     

氧化应激致心室重构的研究进展

心室重构意味着血管壁中氧化应激水平的提高,当机体受到有害刺激时,氧化和抗氧化之间失衡,导致大量活性氧簇（ ROS）的产生,加速心室重构的进展。近年来,新型抗氧化剂成为治疗或预防心室重构的靶点,观察抗氧化剂治疗在心室重构患者的长期应用是当下趋势。该文就氧化应激与心室重构之间的关系及相关药物治疗进行综述。     

二甲基砜在百草枯诱导肺泡Ⅱ型上皮细胞损伤中的保护作用研究

<正>二甲基砜(MSM)的抗炎抗氧化作用近年来逐渐被医学界所关注。百草枯是活性氧(ROS)的有效诱导物,百草枯中毒对肺组织的损伤作用,主要通过促进细胞内产生ROS,导致支气管或肺泡出血、肺间质水肿、低氧血症和白细胞浸润等严重的肺损伤。NF-E2相关因子2(nuclear factor E2-related factor2,NRF2)则是ROS介导的病理生理过程中的关键抗氧化转录因子。已经证实,NRF2具有调节氧化应激的能力,     

Nrf2/ARE信号通路及其调控的抗氧化蛋白

机体在应对活性氧(reactive oxygen species,ROS)损害时形成了一套复杂的氧化应激应答系统,当暴露于ROS时,机体自身能诱导出一系列保护性蛋白,以缓解细胞所受的损害。这一协调反应是由这些保护性基因上游调节区的抗氧化反应元件(antioxidant responsive element,ARE)来调控的。而近年来的研究发现,核因子NF-E2相关因子(nuclear fac-tor erythroid 2-related factor 2,Nrf2)是ARE的激活因子。Nrf2是外源性有毒物质和氧化应激的感受器,在参与细胞抗氧化应激和外源性有毒物质诱导的主要防御机制中发挥重要的作用。Nrf2-ARE通路是迄今为止发现的最为重要的内源性抗氧化应激通路。     

转录因子Nrf2的神经保护作用及其机制

NF-E2相关因子2(Nrf2),感受体内反应活性氧(Reactive oxygen species,ROS)变化后,与体内的锚定蛋白Keap1解聚,发生核转位并调控下游多种抗氧化应激蛋白,解毒酶及转运体基因的表达,参与抗氧化应激生理及病理过程.目前,许多研究发现,Nrf2转录调控的下游靶基因可以对抗由脑中风氧化应激引起的神经系统病变,阿尔茨海默病(Alzheimer's disease),帕金森病(Parkinson's disease),侧索硬化(Amyotrophic lateral sclerosis,ALS).本文对近年来Nrf2在神经保护方面的作用及其机制,以及Nrf2作为药物治疗靶点治疗神经退行性病变的最新研究成果进行总结.     

纳米铜对肾细胞的氧化损伤作用

目的研究氧化应激在纳米铜引起肾细胞毒性中的作用。方法通过检测细胞内活性氧生成、金属硫蛋白表达、谷胱甘肽和丙二醛含量来了解纳米铜对肾细胞的氧化损伤作用。结果纳米铜可以剂量依赖性方式诱导细胞内ROS含量升高。20 mg.L-1纳米铜与细胞作用24 h,细胞内MT表达均明显增强。将0～40 mg.L-1纳米铜与HK-2细胞作用24 h,可引起细胞内GSH,培养上清中的MDA水平均呈剂量依赖性升高,而细胞内MDA、CuZn-SOD水平升高不明显。结论纳米铜在一定剂量和暴露时间条件下破坏了肾细胞内活性氧与抗氧化物质的动态平衡,引起氧化应激,这是纳米铜引起毒性损伤的机制之一。     

五味子乙素抗氧化应激损伤作用及机制的研究进展

机体氧化与抗氧化系统失衡导致氧化应激,产生细胞毒性,引起多种疾病.五味子乙素(γ-Schizandrin B,Sch B)是中药北五味子中的一种具有高抗氧化效能的成分,现已被证明可为实验动物的各种器官组织提供广泛的保护作用以抵抗氧化损伤,为防治各种氧化应激相关疾病提供了研究前景.本研究就五味子乙素抗氧化应激损伤作用及其...     

白藜芦醇对上皮细胞氧化应激保护作用的研究进展

上皮细胞是位于皮肤及腔道表层的细胞,在屏障、分泌、吸收等方面发挥重要功能。氧化应激是指体内氧化与抗氧化作用倾向于氧化的一种失衡状态,是自由基在体内产生的一种负面影响,被认为是导致疾病、衰老及细胞损伤的重要因素。RES是一种存在于多种植物中的天然多酚化合物,具有广泛的生物学特性,近年来,其抗氧化应激作用广受关注。本文就RES对上皮细胞氧化应激的保护作用及机制做一综述。     

内质网应激与氧化应激:恶性循环还是双刃剑?

目的综述内质网应激与氧化应激之间相互作用关系的研究进展。探讨氧化应激与内质网应激相互作用诱发相关疾病的机制。方法阅读国内外文献数据库中相关文献,尤其是近年来关于氧化应激与内质网之间关系的文献,结合临床,从疾病诱发机制等方面对文献进行整理和综述。结果根据疾病背景,促进细胞存活的治疗策略主要在于加强保护未折叠蛋白反应(UPR)信号响应,衰减内质网应激水平,或者灭活UPR促凋亡化合物;而从氧化应激出发,控制氧化应激水平,减弱内质网应激是控制疾病发作的重要方法。结论本文对两种应激关系的研究近况进行整理总结,为相关疾病发病机制的深入研究和临床应用提供理论依据。     

Neuroprotective actions of flavonoids

The experimental evidences accumulated during last years point out a relevant role of oxidative stress in neurodegeneration. As anti-cellular oxidative stress agents flavonoids can act either as direct chemical antioxidants, the classic view of flavonoids as antioxidants, or as modulators of enzymes and metabolic and signaling pathways leading to an overshot of reactive oxygen species (ROS) formation, a more recently emerging concept. Flavonoids, a large family of natural antioxidants, undergo a significant hepatic metabolism leading to flavonoid-derived metabolites that are also bioactive as antioxidant agents. The development of more efficient flavonoid's based anti-oxidative stress therapies should also take into account their bioavailability in the brain using alternate administration protocols, and also that the major ROS triggering the cellular oxidative stress are not the same for all neurodegenerative insults and diseases. On these grounds, we have reviewed the reports on neuroprotection by different classes of flavonoids on cellular cultures and model animals. In addition, as they are now becoming valuable pharmacological drugs, due to their low toxicity, the reported adverse effects of flavonoids in model experimental animals and humans are briefly discussed.     

Mitochondrial dysfunction and targeted drugs: a focus on diabetes

Diabetes is a severe, heterogeneous, multifactorial, chronic disease. Diabetes and oxidative stress are related to continuous and acute overproduction of reactive oxygen species (ROS). These ROS are released principally from mitochondria, but also have other sources. Oxidative stress seems to play an important role in mitochondria-mediated disease processes, though the exact molecular mechanisms responsible remain elusive. ROS are necessary for the proper functioning of the cell, but their excessive production can be harmful, making antioxidant defenses essential. Some substances with antioxidant properties, such as vitamins C and E, have been used to eradicate the oxidative stress associated with diabetes. The results of clinical trials employing anti-oxidative stress reagents in patients with diabetes are contradictory, perhaps due to inadequate study design or the specific targets selected. This review considers the process of diabetes from a mitochondrial perspective and evaluates strategies currently under development for the targeted delivery of antioxidants or other molecules to mitochondria. The evidence compiled herein endorses the selective targeting of specific molecules to mitochondria as an effective strategy for modulating mitochondrial respiration and ROS production and protecting mitochondria against oxidative stress.     

Role of oxidative stress in alcohol-induced liver injury

Reactive oxygen species (ROS) are highly reactive molecules that are naturally generated in small amounts during the body’s metabolic reactions and can react with and damage complex cellular molecules such as lipids, proteins, or DNA. Acute and chronic ethanol treatments increase the production of ROS, lower cellular antioxidant levels, and enhance oxidative stress in many tissues, especially the liver. Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol produces liver injury. Many pathways play a key role in how ethanol induces oxidative stress. This review summarizes some of the leading pathways and discusses the evidence for their contribution to alcohol-induced liver injury. Special emphasis is placed on CYP2E1, which is induced by alcohol and is reactive in metabolizing and activating many hepatotoxins, including ethanol, to reactive products, and in generating ROS.     

蕨麻与脑缺血-再灌注损伤

脑缺血-再灌注损伤是一个复杂的级联反应过程,包括多个环节,近几年研究发现氧化应激与炎症反应与脑缺血-再灌注损伤有着密切关系。因此,抗氧化应激与抗炎症反应治疗在脑缺血-再灌注损伤中愈来愈受到重视。蕨麻作为我国传统藏药之一,药用历史悠久,其药用价值有待进一步发掘。现在学者们已经从蕨麻中提取各种活性成分,经过现代药理研究证实蕨麻具有抗氧化应激、抗炎、保护心肌、提高免疫力、抑制细菌活性及抑癌等作用,但蕨麻是否具有脑缺血-再灌注损伤保护作用尚有待进一步研究。本文就脑缺血-再灌注损伤研究进展与蕨麻的药理作用作一综述。     

Oxidative stress as the leading cause of acute myocardial infarction in diabetics

The risk factors, such as hypertension and metabolic syndrome, tend to promote heart pathology. These risk factors can aggravate concomitant heart insults as well. Diabetes mellitus represents one of the most important risk factors for the development of heart pathology. By itself it represents a source of vascular and heart dysfunction through formation of reactive oxygen species (ROS) and can compromise the recovery from cardiovascular diseases. This review focuses on the evidence that cellular oxidative stress is the leading cause of the worst outcome of myocardial infarction (MI) in diabetics. Hyperglycemia is viewed in this article as the primary mediator of a cascade of heart damaging events, starting from ROS formation and leading to myocardial ischemia, inflammation and death of myocytes. This article also provides insights into why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress and inflammation, can impede or delay the onset of complications of myocardial infarction in diabetic patients.     

Fipronil insecticide toxicology: oxidative stress and metabolism

Fipronil (FIP) is widely used across the world as a broad-spectrum phenylpyrazole insecticide and veterinary drug. FIP was the insecticide to act by targeting the γ-aminobutyric acid (GABA) receptor and has favorable selective toxicity towards insects rather than mammals. However, because of accidental exposure, incorrect use of FIP or widespread FIP use leading to the contamination of water and soil, there is increasing evidence that FIP could cause a variety of toxic effects on animals and humans, such as neurotoxic, hepatotoxic, nephrotoxic, reproductive, and cytotoxic effects on vertebrate and invertebrates. In the last decade, oxidative stress has been suggested to be involved in the various toxicities induced by FIP. To date, few reviews have addressed the toxicity of FIP in relation to oxidative stress. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a possible mechanism for FIP-induced toxicity as well as metabolism. The present review reports that studies have been conducted to reveal the generation of reactive oxygen species (ROS) and oxidative stress as a result of FIP treatment and have correlated them with various types of toxicity. Furthermore, the metabolism of FIP was also reviewed, and during this process, various CYP450 enzymes were involved and oxidative stress might occur. The roles of various compounds in protecting against FIP-induced toxicity based on their anti-oxidative effects were also summarized to further understand the role of oxidative stress in FIP-induced toxicity.     

Paracetamol: overdose-induced oxidative stress toxicity,metabolism, and protective effects of various compounds in vivo and in vitro

Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.     

Role of renal medullary oxidative and/or carbonyl stress in salt-sensitive hypertension and diabetes

1. Salt-sensitive hypertension is commonly associated with diabetes, obesity and chronic kidney disease. The present review focuses on renal mechanisms involved in the development of this type of hypertension. 2. The renal medullary circulation plays an important role in the development of salt-sensitive hypertension. In vivo animal studies have demonstrated that the balance between nitric oxide (NO) and reactive oxygen species (ROS) in the renal medulla is an important element of salt-sensitive hypertension. The medullary thick ascending limb (mTAL) in the outer medulla is an important source of NO and ROS production and we have explored the mechanisms that stimulate their production, as well as the effects of NO superoxide and hydrogen peroxide on mTAL tubular sodium reabsorption and the regulation of medullary blood flow. 3. Angiotensin II-stimulated NO produced in the mTAL is able to diffuse from the renal mTAL to the surrounding vasa recta capillaries, providing a mechanism by which to increase medullary blood flow and counteract the direct vasoconstrictor effects of angiotensin II. Enhanced oxidative stress attenuates NO diffusion in this region. 4. Carbonyl stress, like oxidative stress, can also play an important role in the pathogenesis of chronic kidney disease, such as insulin resistance, salt-sensitive hypertension and renal vascular complications. 5. Despite the large number of studies undertaken in this area, there is as yet no drug available that directly targets renal ROS. Oxidative and/or carbonyl stress may be the next target of drug discovery to protect against salt-sensitive hypertension and associated end-organ damage.     

Effect of gender and sex hormones on vascular oxidative stress

1. It is well documented that the incidence and severity of several vascular diseases, such as hypertension, atherosclerosis and stroke, are lower in premenopausal women than men of similar age and post-menopausal women. The mechanisms responsible for gender differences in the incidence and severity of vascular disease are not well understood. However, emerging evidence suggests that sex hormone-dependent differences in vascular oxidative stress may play an important role. The aim of the present brief review is to provide an insight into the effect of gender and sex hormones on vascular oxidative stress. 2. When production of reactive oxygen species (ROS) is enhanced and/or their metabolism by anti-oxidant enzymes is impaired, a condition known as 'oxidative stress' can develop. Oxidative stress is believed to play an important role in both the initiation and progression of a variety of vascular diseases, including hypertension and atherosclerosis. NADPH oxidases are believed to be the major source of vascular ROS. Moreover, excessive production of ROS by NADPH oxidases has been linked to the development of vascular oxidative stress. 3. Increasing evidence suggests that levels of vascular ROS may be lower in women than men during health and disease. Indeed, the activity and expression of vascular NADPH oxidase is lower in female versus male animals under healthy, hypertensive and atherosclerotic conditions. 4. Gonadal sex hormones may play an important role in the regulation of vascular oxidative stress. For example, oestrogens, which are present in highest levels in premenopausal women, have been reported to lower vascular oxidative stress by modulating the expression and function of NADPH oxidases, as well as anti-oxidant enzymes. 5. Further studies are needed to clarify whether lower vascular oxidative stress in women in fact protects against the initiation and development of vascular disease and to further define the roles of gonadal sex hormones in such an effect. Knowledge gained from these studies may potentially lead to advances in the clinical diagnosis and treatment of vascular disease in both genders.