二乙基二硫代氨基甲酸钠对二氧化硫衍生物引起的心肌细胞钠电流增大的增强效应

超氧化物歧化酶(superoxide dismutase,SOD)是生物体内专一的过氧自由基(superoxide anions,O2.-)清除剂,而二乙基二硫代氨基甲酸钠(diethyldithiocarbamate,DDC)则是公认的Cu,Zn-SOD的抑制剂。采用全膜片钳技术研究了DDC对二氧化硫(sulfur dioxide,SO2)衍生物引起的大鼠心肌细胞钠电流增大效应的作用,以期更进一步揭示SO2的毒性机理。结果表明:SO2衍生物对SOD活性无显著影响,SO2衍生物存在时,DDC仍可以显著降低SOD的活性。DDC(10￣100 mmol/L)剂量依赖性地增大钠电流(INa),半数效应浓度为(19.85±0.95)mmol/L。将20 mmol/L的DDC与10μmol/L的SO2衍生物同时作用于心肌细胞,INa仍表现为电压依赖性的增大,并使INa的电压依赖性激活曲线显著地向负电压方向移动,稳态失活曲线向正电压方向移动,差异极其显著。这表明DDC增强了SO2衍生物对心肌细胞钠电流的增大效应,提示SO2衍生物引起的大鼠心肌细胞毒性主要是通过自由基,特别是O2.-氧化损伤实现的。     

活酵母衍生物对丁(鱼岁)抗氧化能力和部分免疫活性指标的影响

在饲料中添加0.4%活酵母衍生物(LYCD)喂养丁(Tincatinca),对该鱼超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、氧化代谢产物丙二醛(MDA)以及溶菌酶(LYZ)等指标进行测定。结果表明:LYCD可显著提高机体的抗氧化能力;促进鱼体SOD酶的产生,试验与对照组鱼鳃SOD酶活性表现出极显著差异,肝胰脏和脾脏SOD酶的含量显著提高;试验组肝胰脏CAT酶活性极显著升高而氧化代谢产物MDA则极显著下降,脾脏也有显著差异;试验组鱼鳃和肝胰脏组织LYZ活性极显著高于对照组,脾脏LYZ活性也显著提高,而肾脏没有明显变化;同时LYCD还能增加白细胞的吞噬能力,白细胞吞噬指数明显增加     

溶液介电常数对铜锌超氧化物歧化酶活性的影响

溶液介电常数对天然酶和修饰酶的活性影响不同,天然酶随介电常数增加而酶活性下降,修饰酶则反之,这表明静电相互作用在铜锌超氧化物歧化酶(Cu·Zn-SOD)与超氧阴离子(-O_2~(·-))反应过程中起着重要作用,酶分子活性中心附近ε-NH_3~+为O_2~(·-)进入活性中心提供静电吸引力。在有机溶剂中,SOD的构象会发生变化,从而导致酶活性降低。实验还表明,Cl~-对SOD有明显的抑制作用。     

敌百虫对水丝蚓的毒害

采用急性毒性方法测定了被不同浓度敌百虫毒害的水丝蚓(Limnodilus hoffineisteri)半致死浓度(LC50),利用测定酶活性方法检测了水丝蚓超氧化物歧化酶(SOD)的变化及中毒后水丝蚓喂饲的强壮水螅(Hydra robusta)SOD的改变。(1)敌百虫对水丝蚓48 h LC50为3.29 mg/L。敌百虫对水丝蚓SOD活性影响显著(P<0.05):在低浓度1~4 mg/L时,SOD活性呈上升趋势,但随浓度增加至5 mg/L,SOD活性开始下降。(2)用1~8 mg/L中毒后的水丝蚓依次喂饲水螅,SOD活性呈上升趋势。实验结果表明,敌百虫作为重要的杀虫剂或作为防治鱼病的药物,对水丝蚓造成胁迫,并在一定浓度范围内直接或间接地影响以其为食的动物的生存,以至危害生命。     

宾赛克嗪对有机磷中毒合并呼吸衰竭患者氧化应激反应及细胞免疫因子水平的影响

目的:探讨宾赛克嗪对有机磷中毒合并呼吸衰竭患者氧化应激产物及细胞免疫因子的影响。方法:收集我院有机磷中毒合并呼吸衰竭患者84例,分为对照组与实验组。对照组予阿托品治疗,实验组予以宾赛克嗪治疗。分别于治疗前后检测患者超氧化物歧化酶(SOD)活性、丙二醛(MDA)、谷胱甘肽(GSH)含量以及CD4~+、CD8~+、CD4~+/CD8~+、(NK)(CD16~+CD56~+)细胞水平。结果:与治疗前比较,治疗后两组患者氧化应激产物SOD及GSH升高,MDA降低,差异具有统计学意义(P0.05);与对照组比较,实验组治疗后SOD、GSH水平较高,MDA水平较低,差异有统计学意义(P0.05);与治疗前比较,治疗后两组患者细胞免疫因子CD4~+、CD8~+水平升高,CD4~+/CD8~+、(NK)(CD16~+CD56~+)细胞水平降低,差异具有统计学意义(P0.05);与对照组比较,实验组治疗后CD4~+、CD8~+水平较高,CD4~+/CD8~+、(NK)(CD16~+CD56~+)细胞水平较低,差异有统计学意义(P0.05)。结论:宾赛克嗪对有机磷中毒合并呼吸衰竭患者氧化应激产物及细胞免疫因子水平有显著的改善作用,值得临床推广应用。     

生长素介导海藻酸钠寡糖调控水稻对镉胁迫的抗性

采用生长素运输抑制剂,探讨生长素是否介导海藻酸钠寡糖(AOS)缓解水稻镉(Cd)胁迫。结果表明,Cd胁迫明显抑制水稻幼苗的生长发育,表现在苗长、地上部生物量和地下部生物量均有不同程度降低;AOS预处理可显著提高水稻植株超氧化物歧化酶(SOD)、过氧化物酶(POD)和抗坏血酸过氧化物酶(APX)活性,降低O_2~(-·)产生速率,使SOD/O_2~(-·)、SOD/POD、SOD/过氧化氢酶(CAT)和POD/O_2~(-·)的比值增加,丙二醛含量下降,苗长、根长及生物量均有一定程度恢复,但会造成H_2O_2在体内有一定累积。生长素信号被阻断后,AOS预处理(Cd+AOS+Y)对水稻Cd胁迫的缓解效应明显受到削弱,表现为苗长、根长等生长指标和抗氧化酶活性均较生长素信号未阻断处理(Cd+AOS)有所降低,补加外源生长素后(Cd+AOS+Y+NAA),各项指标又有所增加,该结果初步表明,生长素信号介导AOS调控水稻对Cd胁迫的抗性。     

雷公藤红素对抗过氧化氢诱导肌萎缩性侧索硬化症细胞模型氧化损伤的保护作用

本研究旨在探讨在H_2O_2诱导氧化应激损伤条件下,雷公藤红素对肌萎缩性侧索硬化症细胞模型SOD1~(G93A)NSC34的保护作用及其相关分子机制。用不同剂量H_2O_2、雷公藤红素处理表达人突变SOD1~(G93A)基因的NSC34细胞24 h后,CCK-8试剂检测细胞存活率;丙二醛试剂盒检测细胞内丙二醛水平;real-time PCR检测细胞谷氨酸半胱氨酸连接酶催化亚基(glutamatecysteine ligase catalytic subunit,GCLC)和谷胱甘肽硫转移酶(glutathione S-transferases,GST)的表达水平;Western blot检测药物处理后细胞内MEK/ERK和PI3K/Akt细胞信号通路的激活。结果显示,50 nmol/L雷公藤红素预处理可提高H_2O_2(10μmol/L)损伤后SOD1~(G93A)NSC34细胞的生存率,并使细胞内MDA生成减少,逆转H_2O_2诱导的SOD1~(G93A)NSC34细胞内谷胱甘肽合成相关酶GCLC和GST mRNA表达下调。雷公藤红素处理0.5 h、1 h分别激活SOD1~(G93A)NSC34细胞内MEK/ERK和PI3K/Akt信号通路达峰值,且MEK抑制剂PD98059和Akt抑制剂MK2206可阻断雷公藤红素对相关信号通路的激活效应。PD98059、MK2206预处理30 min均抑制雷公藤红素引起的SOD1~(G93A)NSC34细胞内GCLC和GST上调。以上研究结果提示,雷公藤红素对肌萎缩性侧索硬化症细胞模型SOD1~(G93A)NSC34细胞有抗氧化应激的保护作用,该神经保护作用与雷公藤红素调节SOD1~(G93A)NSC34细胞内谷胱甘肽合成相关酶类生成有关,细胞内MEK/ERK和PI3K/Akt信号通路参与此调节过程。     

蚯蚓超氧化物歧化酶理化性质的研究

从蚯蚓中提取超氧化物歧化酶(Superoxide Dismutase简称SOD),经硫酸铵分级沉淀分离、透析除盐后测定SOD活性得知:50~70%饱和度硫酸铵沉淀的SOD活性最高,比活性也最高;蚯蚓体内此酶在35~40℃之间表现出最高活性;最适pH值为7.8~8.2;提取蚯蚓SOD的最适提取液体积应为蚯蚓鲜重的4倍(v/w)。     

血卟啉衍生物(BHPD)光敏反应的原初过程Ⅰ.活性氧的产生

为了阐明血卟啉衍生物(HPD)的光敏作用机理,本文以我国自行研制、并已应用的第一代产品——北京血卟啉衍生物(简称BHPD)为对象,采用电子自旋共振(ESR)和自旋捕捉(Sping-Traping)等技术,从光生物物理角度,探讨了BHPD光敏反应的原初过程.结果表明,不仅观察到~1O_2的产生,而且还观测到O_2~(?)和·OH的产生.这提示,在BHPD对生物系统的光敏损伤过程中,不只是~1O_2,O_2~(?)和·OH等活性氧,很可能也起重要作用.     

二氧化硫衍生物对蚕豆幼苗生长和细胞周期的影响

研究SO₂体内衍生物NaHSO₃与Na₂SO₃(1:3,mmol/L)对蚕豆幼苗生长和细胞分裂的影响。结果表明:SO₂衍生物(浓度在0~30mmol/L)对幼苗生长的抑制作用具有剂量效应和时间效应关系,短时间处理效应不明显,处理48h后蚕豆幼根生长抑制,168h后幼苗根上部分长度(芽长)表现生长抑制,根长和芽长与处理浓度间呈负线性相关。SO₂衍生物处理12~36h,导致根尖细胞分裂指数下降,根尖中前期细胞减少,间期、后期和末期细胞增多,表明SO₂衍生物能够阻止细胞进入分裂态,延长分裂过程,这可能是SO₂衍生物处理组根尖细胞分裂指数降低,幼苗生长抑制的主要原因。     

Tween类胶束体系中水杨酸铜络合物的SOD样活性

合成了水杨酸铜·乙醇络合物,提纯了Ｔｗｅｅｎ－２０、Ｔｗｅｅｎ－４０,Ｔｗｅｅｎ－６０．Ｔｗｅｅｎ－８０,并测定了它们在ｐＢ７．４的磷酸缓冲液中的ＣＭＣＯ。用Ｃｙｔ,ｃ－ＨＸ－ＸＯ法分别测定了水杨酸铜·乙醇络合物清除超氧阴离子自由基的活性,不同浓度的单纯表面活性剂对Ｏ２的影响,以及表面活性剂与水杨酸铜·乙醇络合物协同清除Ｏ２的作用。观察到在胶束体系中水杨酸铜·乙醇络合物的ＳＯＤ样活性明显高于缓冲液体系无表面活性剂时的ＳＯＤ样活性,表面活性剂本身也具有清除Ｏ２的功能。抗红细胞膜脂质过氧化实验也得到类似结果。     

Relationship between total superoxide dismutase activity with lipid peroxidation, dynamics and morphological parameters in canine semen

There is a lack of information regarding biochemical studies on canine semen. The knowledge of canine sperm metabolism is important because this species has differences in fertility among males, but biochemical studies are not well developed in this species. Reactive oxygen species (ROS) are active molecules produced during the oxygen reduction that have been implicated in several deleterious effects on the function and viability of spermatozoa when they are produced at high concentrations. Peroxidation of the plasma membrane phospholipids leads to a loss of motility, viability, and cytosolic elements, metabolic changes and structural alterations in spermatozoa. The most important antioxidant enzyme involved in ROS detoxification in mammalian spermatozoa is superoxide dismutase (SOD). The aims of the present study were to determine the presence of SOD-like activity in different fractions of canine semen, and to determine the relationship between SOD-like activity and different morphological, dynamical and biochemical parameters in canine spermatozoa. We demonstrated the presence of SOD-like activity in canine seminal plasma and spermatozoa; the negative correlation between SOD-like activity and lipid peroxidation concentrations in spermatozoa suggests a protective effect of this enzymatic activity against the potential oxidative stress in canine spermatozoa. A significant negative correlation between percentage of abnormal spermatozoa, and the percentage of progressive motility or vigor was found. Abnormal spermatozoa not only showed a deformed shape, moreover there was an energetic motility system failure. The presence of SOD-like activity in seminal plasma, spermatic, and postspermatic fractions of canine semen was demonstrated for the first time.     

Synthesis,anti-HIV and anti-oxidant activities of caffeoyl 5,6-anhydroquinic acid derivatives

In our continued research on chlorogenic acid analogues and derivatives with improved bioactivity, we have synthesized some caffeoyl 5,6-anhydroquinic acid derivatives. The 1,7 acetonides of chlorogenic acid (15), and of the mono-caffeoyl 5,6-anhydroquinic acids (7–8) showed appreciable anti-HIV activity. The 3,4-dicaffeoyl 5,6-anhydroquinic acid (12) exhibited an anti-HIV activity twice as that of 3,5-dicaffeoylquinic acid (22). The caffeoyl 5,6-anhydroquinic acid derivatives displayed potent anti-oxidant activities. The mono-caffeoyl 5,6-anhydroquinic acids (10–11) were more than twice stronger than chlorogenic acid (21) on SOD-like activity.     

Antiinflammatory and antioxidant evaluation of novel coumarin derivatives

Several coumarin derivatives have been reported to present multiple biological activities and especially antiinflammatory/antioxidant activities. Recently the synthesis and in vivo/in vitro anti-inflammatory/antioxidant activities of several new coumarin derivatives with a 7-azomethine linkage have been reported. In the present study these derivatives were further tested for their antioxidant ability. Some of them were found in vitro to inhibit lipid peroxidation and to strongly scavenge superoxide radicals. Compound 3 was found to potently inhibit cyclooxygenase-1 (COX-1) and the yeast-induced rat paw oedema. The most active compounds within the set were tested against adjuvant-induced arthritis. Compound 3 was found to significantly protect the rats from adjuvant-induced arthritis (when it is administered from the first day or when it is administered the fourteenth day, with the first symptoms of the disease). An attempt was made to delineate the possible mechanism of action of the studied compounds.     

Superoxide anion and hydroxyl radical scavenging activities of vegetable extracts measured using electron spin resonance.

Radical scavenging by reconstituted lyophilized powders of water extracts from 16 common vegetables was measured using electron spin resonance (ESR) with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), hydroxyl radicals, (.OH) or superoxide anion radicals (O2.-), as DMPO-OH or DMPO-OOH spin adducts. On a dry weight basis, eggplant, and red, yellow and green bell pepper extracts showed potent superoxide anion radical scavenging activities (SOD-like activities). Ascorbate oxidase- or heat-treatments, decreased SOD-like activities in bell pepper extracts suggesting that ascorbate accounts for much of their free radical scavenging activity. Eggplant epidermis extract exhibited the most potent hydroxyl radical scavenging and SOD-like activities. Eggplant SOD-like activity did not decrease after ascorbate oxidase treatment, but decreased following ultrafiltration demonstrating that SOD-like activity is partially due to high molecular weight substances. Nasunin, an anthocyanin in eggplant epidermis, showed markedly potent superoxide anion radical scavenging activity, while it inhibited hydroxyl radical generation probably by chelating ferrous ion.     

Sugar levels in Charmat sparkling wines can affect the quality and resveratrol levels

Sparkling wines contain CO(2) obtained through a second fermentation by natural processes (Charmat method); they may be prepared with variable final sugar concentrations, resulting in physicochemical compositions and phenolic profiles different to those obtained with other natural methods. The purpose of this study was to verify the influence of sweetness on enological parameters, trans-resveratrol and trans-piceid levels, antioxidant capacity (power of scavenger the radical DPPH(?) (1,1-diphenyl-2-picrylhydrazyl) and mimetic enzymatic activities of superoxide dismutase (SOD-like) and catalase (CAT-like) assays, and β-glucosidase activities on Charmat sparkling wines. The interaction of polyphenol levels and sweetness was observed. Levels of trans-piceid and trans-resveratrol showed a decrease in function of glucose concentration up to 40 g/l. All samples showed antioxidant capacity and β-glucosidase activity was stable even in the presence of sugar. A positive correlation between SOD-like and DPPH(?) was observed. This work shows an approach able to clarify important aspects for the wine industry with regard to world-wide consumer demand for sweetened products.     

Nitrone derivatives of trolox as neuroprotective agents

Synthesis of nitrone derivatives of trolox is described. Their biological evaluation was performed in vitro for scavenging different free radicals, inhibiting Fe(2+)-induced lipid peroxidation, and in vivo in a permanent middle cerebral artery occlusion model in mice. New compounds exert pharmacological activities comparable to or better than those of trolox or nitrone-type reference compounds.     

Anthocyanins protect against DNA damage induced by tert-butyl-hydroperoxide in rat smooth muscle and hepatoma cells

Anthocyanins are flavonoids present in a variety of pigmented food and, like other flavonoids, seem to play a role in preventing human pathologies related to oxidative stress. In fact, anthocyanins have been shown to exert antiproliferative effects in cell cultures and exhibit antiinflammatory and vasoprotective activities in animal models. Although these biological activities have been related to their antioxidant properties, little is known on the molecular mechanism of action of anthocyanins. The effects of pretreatment with the anthocyanins delphinidin, cyanidin, and their glycoside and rutinoside derivatives against induction of DNA damage induced by tert-butyl-hydroperoxide (TBHP) were evaluated in rat smooth muscle and in rat hepatoma cell lines using alkaline single cell gel electrophoresis (Comet test). In addition, a possible protection exerted by anthocyanins on cell killing, lipid peroxidation, and redox state alterations induced by TBHP was also investigated. It was found that the treatment with TBHP induces the formation of DNA single strand breaks (SSB) and oxidised bases, along with cell killing, lipid peroxidation and redox state alteration. Our data demonstrate that anthocyanins are effective against cytotoxicity, DNA SSB formation and lipid peroxidation induced by TBHP, but they do not have any detectable effect against impairment by TBHP of cellular redox state and on protection against DNA bases oxidation. The presence of a sugar moiety in anthocyanin derivatives reduced this protective effect, mainly in rat hepatoma cells. The different activity of anthocyanins and their derivatives may be explained taking into account a structure/function relationship that could also influence anthocyanin intracellular localisation.     

The mechanisms of nucleotide actions in insulin resistance

Insulin resistance contributes to metabolic disorders in obesity and type 2 diabetes. In mechanisms of insulin resistance, the roles of glucose, fatty acids, and amino acids have been extensively documented in literature. However, the activities of nucleotides remain to be reviewed comprehensively in the regulation of insulin sensitivity. Nucleotides are well known for their activities in biosynthesis of DNA and RNA as well as their signaling activities in the form of cAMP and cGAMP. Their activities in insulin resistance are dependent on the derivatives and corresponding receptors. ATP and NADH, derivatives of adenosine, inhibit insulin signaling inside cells by downregulation of activities of AMPK and SIRT1, respectively. ATP, ADP and AMP, the well-known energy carriers, regulate cellular responses to insulin outside cells through the purinergic receptors in cell surface. Current evidence suggests that ATP, NADH, cGAMP, and uridine are potential biomarkers of insulin resistance. However, GTP and cGMP are likely the markers of insulin sensitization. Here, studies crossing the biomedical fields are reviewed to characterize nucleotide activities in the regulation of insulin sensitivity. The knowledge brings new insights into the mechanisms of insulin resistance.     

Synthesis of naphthalimide derivatives with potential anticancer activity,their comparative ds- and G-quadruplex-DNA binding studies and related biological activities

Molecular Biology Reports - Two new cytotoxic 1,8-naphthalimide derivatives have been synthesized and characterized. Their biological activities as cytotoxicity and antimicrobial activities and...