广义刺激剂量-生物效应理论、模型和应用

目的:试图从理论上提出广义刺激生物效应多样性的广义刺激剂量生物效应理论,建立统一广义刺激生物效应理论和理论模型,定量描述和解释广义刺激生物效应的多样性。方法:总结提出广义刺激剂量生物效应理论的6个原理,建立统一剂量广义刺激生物效应理论和理论模型。结果:根据广义刺激生物效应多样性的广义刺激剂量生物效应理论,建立了8个广义刺激剂量生物效应方程,可以定量描述和解释广义刺激生物效应的多样性。结论:建立的广义刺激剂量生物效应理论和理论模型,定量描述和解释广义刺激剂量生物效应:一般损伤效应、低剂量兴奋性效应、旁效应和超敏效应等。该理论和理论模型适用于广义刺激:物理因子(辐射等)、化学因子(毒物等)、生物因子(细菌、病毒等)、心理、药物、毒物、信息等刺激剂量生物效应关系,可称为广义刺激剂量生物效应理论和理论模型,具有重要的学术意义和应用价值。     

缺血性脑血管疾病治疗的抗氧化应激策略

自由基是细胞呼吸及正常代谢过程中产生的高活性分子 ,氧化应激 (OS)是细胞内自由基生成和清除能力失衡 ,是缺血性脑血管疾病重要病理反应过程。缺血性脑损伤后 ,活性氧自由基 (ROS)增加 ,以不同的细胞分子机制引起组织损伤。自由基可以损伤细胞内脂质、蛋白质、核酸等重要物质 ,继而通过坏死或凋亡的方式引起细胞死亡。抗氧化剂可防止脑组织损伤 ,改善神经细胞存活率及功能。本文就治疗缺血性脑血管疾病的抗氧化剂作一综述 ,并分析动物与临床试验结果不一致的原因 ,提出缺血性脑血管疾病治疗的抗氧化应激策略。     

灵芝多糖肽对自由基所致的腹腔巨噬细胞早期损伤的影响

目的　以膜电位方法进一步研究灵芝多糖肽(GLPP)对自由基损伤的巨噬细胞线粒体的影响。方法　以叔丁基氢过氧化物(tBOOH)为氧化剂,建立小鼠巨噬细胞体外氧化损伤模型,以罗丹明1 2 3(Rh1 2 3 )为荧光染色剂,以激光共聚焦显微镜检测细胞线粒体膜电位改变。结果　tBOOH氧化剂可损伤线粒体膜,使线粒体膜电位降低,GLPP体内( 1 0 0mg·kg- 1 ig 5d)及体外给药(GLPP 1 0mg·L- 1)均可对抗tBOOH自由基损伤,可使因自由基损伤而降低的巨噬细胞线粒体膜电位恢复。结论　GLPP体内体外给药可减轻自由基损伤,使损伤的线粒体膜电位恢复     

葡萄籽及其保健功能研究应用概述

随着近年来研究的深入,发现葡萄籽具有很高的营养价值和药用价值及其含有抗氧化剂原花青素的活性成分,清除自由基,降血脂,抗癌作用。为此,本文就葡萄籽原花青素近年来的研究做一个简短的概述。     

薄芝糖肽注射液对小鼠腹腔巨噬细胞自由基损伤作用的研究

目的 探讨薄芝糖肽对小鼠腹腔巨噬细胞自由基损伤的作用.方法 用过氧化氢(H2O2)作为氧化剂建立小鼠腹腔巨噬细胞自由基损伤模型;用MTT比色法测定不同药物浓度下的细胞代谢率.结果 实验组不同浓度薄芝糖肽注射液各组的OD值均高于对照组,且OD值随浓度升高逐渐增加.结论 薄芝糖肽对自由基所致小鼠腹腔巨噬细胞损伤有一定的保护作用,且其作用与浓度有一定相关性.     

马齿苋提取物体外清除自由基活性的研究

目的:研究马齿苋全草提取物体外的抗氧化活性。方法:选取1,1-二苯基-2-三硝基苯肼(1,1-diphenyl-2-picryl-hydrazine,DPPH)自由基、羟基自由基、超氧阴离子自由基,以及还原能力体系对马齿苋提取物进行抗氧化活性测定。与阳性对照药没食子酸和维生素C作比较。结果:马齿苋提取物清除DPPH自由基、羟基自由基和超氧阴离子自由基的能力在低浓度时弱于阳性对照药没食子酸和维生素C,但随着浓度的增加,其清除活性均明显优于阳性对照药。在0~200μg/ml浓度范围内,马齿苋提取物的还原能力弱于2,6-二叔丁基对甲酚。结论:马齿苋提取物具有较好的清除自由基能力,但还原能力相对较弱。马齿苋可能是有效的外源性天然有机抗氧化剂。     

氧化应激和阿尔茨海默病

阿尔茨海默病(Alzheimer’sdisease,AD)是一种以进行性认知功能障碍和记忆力损害为主的中枢神经系统退行性疾病,该病是由多种因素共同作用引起的,其中自由基损伤在发病机理中起重要作用。据报道,抗氧化剂在延缓AD病的进程和改善认知能力上有一定疗效。本文就氧化应激自由基损伤与AD的关系以及抗氧化剂研究现状作一综述。     

低剂量辐射过程中的自由基损伤及药物防护

目的:探讨低剂量辐射过程中自由基损伤机制及防护措施。方法:检索近年来国内外有关低剂量辐射过程中自由基的损伤机制、检测及防护等方面文献报道进行归纳和总结。结果:低剂量辐射可诱导自由基产生过多导致机体损伤。多糖、黄酮、多酚类等物质能清除自由基,具有抗辐射的作用。结论:低剂量辐射与自由基的产生呈显著相关,因低剂量辐射而导致的自由基对机体的损伤可通过多种物质进行防护。     

薄芝糖肽注射液对小鼠腹腔巨噬细胞自由基损伤作用的研究

目的探讨薄芝糖肽对小鼠腹腔巨噬细胞自由基损伤的作用。方法用过氧化氢（H2O2）作为氧化剂建立小鼠腹腔巨噬细胞自由基损伤模型;用MTT比色法测定不同药物浓度下的细胞代谢率。结果实验组不同浓度薄芝糖肽注射液各组的OD值均高于对照组,且OD值随浓度升高逐渐增加。结论薄芝糖肽对自由基所致小鼠腹腔巨噬细胞损伤有一定的保护作用,且其作用与浓度有一定相关性。     

依达拉奉对脑缺血再灌注损伤的保护机制

依达拉奉是一种合成的新型自由基清除剂和抗氧化剂,对缺血再灌注损伤具有神经保护作用,可通过消除自由基、抑制脂质过氧化减轻氧化应激损伤;通过调控凋亡相关基因的表达,抑制神经细胞的凋亡;并通过减少炎症因子的产生从而减轻脑缺血及脑缺血引起的水肿和组织损伤。本文主要综述依达拉奉在脑缺血再灌注损伤中保护作用机制的研究进展,为临床应用提供理论依据。     

羟自由基和脑缺血

羟自由基是一种活性高、毒性大的自由基,它在脑缺血及其再灌注的损伤中起着重要的作用,是自由基造成神经细胞死亡的关键环节之一。本文从以下几个方面加以综述,脑缺血中羟自由基产生的可能途径;脑缺血中羟自由基的变化;羟自由基在脑缺血性神经元损伤中的作用以及羟自由基清除剂对脑缺血的保护作用。     

Beneficial and harmful effects of thiols

Biothiols are extraordinarily efficient antioxidants protecting the cells against consequences of damage induced by free radicals, due to their ability to react with the latter. In such antioxidant reactions, thiols undergo one-electron oxidation with the formation of thiyl radicals. For this reason, attention has been focused mostly on antioxidant properties of thiols. Considerably less attention has been paid to thiyl radicals (RS*) formed simultaneously in these reactions. However, protective and repairing efficacy of thiols depends not only on their capacity to detoxify free radicals but also on chemical character and reactivity of the formed thiyl radical. Furthermore, quick and efficient removal of RS radical leads to a disturbance in balanced state of antioxidant reaction, which effectively increases repairing capacity. Dangerous thiyl radicals, which can cause peroxidative injury, should immediately undergo regenerative reduction to thiols. Under physiological conditions, thiyl radicals can react with thiolate anion yielding disulfide radical anion (RSSR)-* as an intermediate and finally disulfides and superoxide radical anion (O2-*), which is next inactivated in the reaction catalyzed by superoxide dismutase (SOD). Thiyl radicals can also be reduced to thiols by reacting with ascorbate with the formation of low-activity ascorbyl radical, that subsequently enters disproportiation reaction.     

Effect of Cervus korean TEMMINCK var. mantchuricus Swinhoe on protease activities, antioxidant and free radical damages in rheumatis arthritis rats.

The effect of deer antler extracts (DAA) of Cervus korean TEMMINCK var. mantchuricus Swinhoe on protease activities, oxidant and free radical damages in synovial fluid from rheumatoid arthritis in rats was studied. Rats were i.p. administered with DAA. We have compared (using the same series of experimental samples) the levels of activity of a comprehensive range of cytoplasmic, lysosomal and matrix protease types, together with the levels of free radical induced protein damage (determined as protein carbonyl derivative) and total antioxidant in synovial fluid from rheumatoid arthritis (RA) and DAA-treated rats. Many proteases activities were shown to be significantly increased in RA compared to normal rats. Protease activities (including those enzyme types putatively involved in the immune response, such as dipeptidyl aminopeptidase IV) in plasma were not significantly different between RA and normal rats. DAA treatment at dose of 100 microg/kg suppressed the production of the proteases of cytoplasmic, lysosomal and matrix protease types. The level of free radical induced damage to synovial fluid proteins was approximately 2-fold lower in DAA rats compared to RA rats, although there was no significant difference in total antioxidant status in synovial fluid or plasma between RA and DAA rats. It was concluded that DAA treatment reduces the activation of proteolytic enzymes and free radicals, which are likely to be of equal potential importance as protein damaging agents in the pathogenesis of RA.     

Superoxide and nitric oxide in pathological conditions associated with iron overload: the effects of antioxidants and chelators

Free radicals are a one of damaging factors in diseases associated with iron overload. This review considers two principal questions: the mechanisms of free radical-mediated damage in cells and tissue and findings concerning the discovery of iron-stimulated free radical cascades in thalassemia and Fanconi anemia. There are two major precursors of all reactive oxygen and nitrogen species formed in living organism - superoxide (O(2)( -)) and nitric oxide (NO). However, it has been shown that in addition to well-known mechanisms of the formation of reactive hydroxyl radicals and peroxynitrite from superoxide and NO, there are signal pathways by which these "physiological" radicals directly induce apoptosis, proton leak in mitochondria and an increase in oxygen consumption leading to cell death. In present review the mechanisms of free radical damage are considered with the particular emphasis of iron-induced free radical formation in thalassemia and Fanconi anemia. Furthermore free radical reactions leading to lipid peroxidation, LDL oxidation, the stimulation of apoptosis and other damaging processes are discussed. An importance of the chelating and antioxidant treatments of thalassemic and Fanconi anemia patients is also considered within the context of free radical damage and its prevention.     

Prevention of doxorubicin-induced acute cardiotoxicity by an experimental antioxidant compound

Doxorubicin is a widely used anticancer agent, but its application is restricted by its cardiotoxic side effects. The current theory of its cardiotoxicity is based on free radical formation. The compound H-2545, having a 3-carboxamido-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole moiety, was reported to exhibit antioxidant properties and accumulate in cell membranes, scavenging free radicals at the site of formation. Therefore, we hypothesized that H-2545 could reduce the doxorubicin-induced acute deterioration of cardiac function. Langendorff-perfused rat hearts were treated with doxorubicin and/or H-2545, its metabolite H-2954, or dihydrolipoamide. High-energy phosphate levels, contractile function, lipid peroxidation, protein oxidation, and Akt phosphorylation were investigated. We also determined whether the antioxidants influenced doxorubicin toxicity on malignant cells. During perfusion with doxorubicin, the energetic and functional parameters of the myocardium were improved by adding H-2545. H-2545 significantly diminished doxorubicin-induced lipid and protein damage. On H-2545 treatment, the doxorubicin-triggered Akt phosphorylation was markedly reduced, whereas dihydrolipoamide had such an effect only at higher concentrations. H-2545 did not alter the anticancer effect of doxorubicin on malignant cell lines. We propose that the coadministration of the antioxidant H-2545 attenuates doxorubicin-induced acute cardiotoxicity without interfering with its anticancer effects. Prevention of the acute adverse effects of doxorubicin on myocardium may hinder the later development of cardiomyopathy.     

Recent developments for SPIE-IA, a new sandwich immunoassay format for very small molecules

Recent publications describing new elegant approaches to assay small analytes using noncompetitive format were briefly reviewed. Among these methods, we have developed a new protocol, named SPIE-IA, which involves a cross-linking step achieved using chemical hombifunctional reagents, UV irradiation or free radicals. This new method proved to be useful to detect naturally occurring analyte/antibody complexes or to protect the analytes against degradation by peptidases. On the other hand, SPIE-IA could allow to study the adverse biological effects of UV and some aspects of free radical chemistry or to evaluate the antioxidant activity of molecules.     

An overview of erdosteine antioxidant activity in experimental research.

Erdosteine was introduced in the market as a mucolytic agent for chronic pulmonary diseases more than 10 years ago. The drug contains two blocked sulphydryl groups one of which, after hepatic metabolization and opening of the thiolactone ring, becomes available both for the mucolytic and free radical scavenging and antioxidant activity too. There are several experimental evidences which support the protective effect of erdosteine in acute injury induced by a variety of pharmacological or noxious agents, mediated by products of oxidative stress. Experimental data in animal assigned to receive the noxious agent evidence that co-treatment with erdosteine increases the tissue antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase, compared with the toxic agent alone; meanwhile erdosteine decreases the tissue level of nitric oxide, xanthine oxidase, which catalyze oxygen-free radical production. In summary, erdosteine prevents the accumulation of free oxygen radicals when their production is accelerated and increases antioxidant cellular protective mechanisms. The final result is a protective effect on tissues which reduces lipid peroxidation, neutrophil infiltration or cell apoptosis mediated by noxious agents. Recent positive clinical trials in humans seem to fulfill the impressive promises that theory and experimental research have put forward.     

Characterization of the radical scavenging and antioxidant activities of danshensu and salvianolic acid B.

Danshensu (3-(3,4-dihydroxyphenyl) lactic acid) and salvianolic acid B, two natural phenolic acids of caffeic acid derivatives isolated from Salvia miltiorrhiza root of the most widely used traditional Chinese medicine for the treatment of various cardiovascular diseases, have been reported to have potential protective effects from oxidative injury. To better understand their biological functions, the in vitro radical scavenging and antioxidant activities of danshensu and salvianolic acid B were evaluated along with vitamin C. Both danshensu and salvianolic acid B exhibited higher scavenging activities against free hydroxyl radicals (HO()), superoxide anion radicals (O(2)(-)), 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals and 2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radicals than vitamin C. In contrary, danshensu and salvianolic acid B showed weaker iron chelating and hydrogen peroxide (H(2)O(2)) scavenging activities than vitamin C. As expressed as vitamin C equivalent capacity (VCEAC), the relative VCEAC values (mg/100ml) were in the order of salvianolic acid B (18.59) > danshensu (12.89) > vitamin C (10.00) by ABTS radical assay. The protective efficiencies against hydrogen peroxide induced human vein vascular endothelial cell damage were correlated with their antioxidant activities. Analysis of structure-activity relationship of these two compounds showed that the condensation and conjugation of danshensu and caffeic acid appears important for antioxidant activity. These results indicated that danshensu and salvianolic acid B are efficient radical scavengers and antioxidants, and salvianolic acid B is superior to danshensu. Their radical scavenging and antioxidant properties might have potential applications in food and healthcare industry.     

An investigation of the novel anti-inflammatory agents ONO-3144 and MK-447. Studies on their potential antioxidant activity

Oxygen-derived free radicals have been implicated as contributors to inflammatory disorders and it has been suggested that certain anti-inflammatory drugs act by scavenging free radicals. In this paper we have studied the free radical scavenging activity of two such experimental anti-inflammatory drugs MK-447 and ONO-3144. Using the technique of pulse radiolysis we have been able to obtain rate constants for the reactions of these compounds with specific free radicals including OH and O2-. We have also investigated the antioxidant capacity of these compounds using rat liver microsomal lipid peroxidation systems. It is suggested that this approach yielding quantitative data concerning defined free radical species will lead to a better understanding of the role of radical scavenging in anti-inflammatory activity.