脂质过氧化在再灌流性肝损伤中的作用

采用低流率-再灌流模型研究脂质过氧化在再灌流性肝损伤中的作用,肝脏经过90min低速率灌流未见明显损伤,当灌流速率恢复到正常后中心静脉周围区(PC区)细胞发生迅速不可逆损害,并伴有丙二醛生成率大幅度上升,低速率灌流期间,灌流液中黄嘌呤与次黄嘌吟浓度由原来的1.5和3.6μmol·L~(-1)逐步升高至5.5和11.5μmol·L~(-1),自由基清除剂儿茶酸能使再灌流期丙二醛生成率由295 nm01·g~(-1)·h~(-1)下降至109 nmol·g~(-1)·h~(-1),并使LDH释放率减少约50％,PC区细胞死亡率减少89％,再灌流初期用氮饱和灌流液冲洗3 min,使再灌流所致的LDH释放下降约50％,PC区细胞死亡率减少84％,别嘌吟醇(2～6mmol·L~(-1))对防止再灌流性肝损伤表现出明显的剂量效应关系。 与预计结果相反低浓度别嘌呤醇(0.5～1mmol·~(-1))能增加再灌流性肝损伤,400μmol·L~(-1)黄嘌呤则使再灌流性肝损伤明显减轻,其代谢产物尿酸对降低再灌流时丙二醛生成率以及细胞损害均表现出明显的剂量反应关系。     

山葡萄籽多酚类化合物体外抗氧化活性的研究(英文)

目的:本文对分自山葡萄籽中的五种多酚类化合物( )-儿茶素、原花青素B_2、原花青素B_5、原花青素B_5-3′-O-gallate和山葡萄素进行抗脂质过氧化研究。方法:采用体外抗小鼠肝匀浆脂质过氧化的方法对这些化合物的抗氧化活性进行评价。结果:( )-儿茶素,原花青素B_2,原花青素B_5,原花青素B_5-3′-O-gallate和山葡萄素等五种化合物对小鼠肝匀浆过氧化脂质生成的半数抑制浓度(IC_(50))分别为0.47、0.25、0.10、0.02及0.03mmol/L,阳性对照维生素E的IC_(50)为0.13mmol/L。对这些化合物的构效关系进行的初步分析表明:带有没食子酰基的多酚具有更强的抗氧化活性,二聚体的抗氧化活性均比单体( )-儿茶素的活性强。另外,4→6连接的二聚体比4→8连接的二聚体具有更强的抗氧化活性。结论:原花青素B_5、原花青素B_5-3′-O-gallate及山葡萄素的抗氧化活性都比维生素E强,且这类多酚的抗氧化活性强弱与取代类型及聚合方式密切相关。     

云南甘草总皂甙清除氧自由基和抗脂质过氧化作用

云南甘草总皂甙(SGY)对Fenton反应生成的·OH具有较强的直接清除作用,其IC_(50)为29mg·L~(-1).且作用明显强于·OH特异性清除剂甘露醇(其IC_(50)为2.27×10~(-2)mol·L~(-1).即4315mg·L~(-1))。SGY对黄嘌呤-黄嘌呤氧化酶系统产生的O_2~+也有较强的清除作用·其IC_(50)为89mg·L~(-1)SGY对自由基发生系统(FRGS)诱导离体大鼠心肌匀浆组织产生的脂质过氧化(LPO)作用有明显的抑制效应.对FRGS诱导离体大鼠心肌线粒体膜LPO也有一定的抑制作用。结果提示SGY的抗脂质过氧化作用与其清除氧自由基作用有关。     

泰山四叶参多糖体外抗氧化活性的研究

目的观察泰山四叶参多糖(PCL)体外抗氧化作用。方法羟自由基(.OH)由Fenton反应体系产生,超氧阴离子(O2-)由邻苯三酚自氧化法产生,硫代巴比妥酸法测定肝匀浆丙二醛(MDA)相对含量反映PCL对脂质过氧化的影响,并观察PCL对H2O2诱导红细胞溶血的影响。结果PCL能显著清除.OH,抑制小鼠肝匀浆脂质过氧化反应,EC50和IC50分别为230.2和479.0μg/mL,并能清除O2-和抑制H2O2诱导的氧化性溶血,EC50和IC50分别为1 048.5和1 674.2μg/mL。结论PCL有较强的体外抗氧化作用,其活性与剂量呈正相关。     

海绵polymistia spongia提取物aldisin的抗脂质过氧化及清除自由基作用研究

目的研究海绵ｐｏｌｙｍｉｓｔｉａｓｐｏｎｇｉａ提取物ａｌｄｉｓｉｎ的抗脂质过氧化及清除自由基作用。方法采用ＭＤＡ－ＴＢＡ比色法测定组织匀浆中过氧化脂质（ＬＰＯ）含量；采用邻苯三酚自氧化法测定ａｌｄｉｓｉｎ对Ｏ·２自由基的清除作用；采用分光光度法测定ａｌｄｉｓｉｎ对Ｃｕ２＋－ＶｉｔＣ体系产生的·ＯＨ自由基的清除作用；采用ＥＳＲ法测定ａｌｄｉｓｉｎ对ＤＰＰＨ自由基的清除作用。结果ａｌｄｉｓｉｎ具有显著的抗脂质过氧化作用，并能有效地清除Ｏ·２、·ＯＨ和ＤＰＰＨ自由基，在０．４２６μｍｏｌ·Ｌ－１～１８．５ｍｍｏｌ·Ｌ－１浓度范围内有明显的量效关系。结论ａｌｄｉｓｉｎ是自由基清除剂。     

新疆两色金鸡菊抗脂质过氧化及清除亚硝酸盐和阻断亚硝胺形成的能力

目的 考察新疆两色金鸡菊的乙酸乙酯和正丁醇提取物抗脂质过氧化及清除亚硝酸盐和阻断亚硝胺形成的能力.方法 采用响应面优化工艺条件提取新疆两色金鸡菊.提取物经石油醚萃取后,剩余水相分别用乙酸乙酯和正丁醇萃取,获得乙酸乙酯提取物(EAE)和正丁醇提取物(BE).采用硫代巴比妥酸法测定提取物的抗脂质过氧化能力;采用盐酸萘乙二胺法测定提取物清除亚硝酸盐和抑制亚硝胺形成的能力.结果 在亚油酸反应体系下,测得EAE和BE的抗脂质过氧化能力(SC50)分别为443.96±11.24、840.29±16.38 μg·mL-1.EAE的抗脂质过氧化能力与阳性对照维生素C之间无显著性差异;但显著弱于阳性对照叔丁基对羟基茴香醚.采用大鼠肝细胞匀浆反应体系测得的结果分别为23.59±3.67、60.37±4.27 μg·mL-1.EAE的抗脂质过氧化能力强于维生素C;但显著弱于叔丁基对羟基茴香醚.在清除亚硝酸盐和阻断亚硝胺形成的能力中,EAE和BE清除亚硝酸盐的能力(SC50)分别为122.10±1.03、118.23±1.30 μg· mL-1;阻断亚硝胺形成的能力分别为2.3629 ±0.0113、2.1828±0.0107 mg·mL-1.两种提取物清除亚硝酸盐和阻断亚胺形成的能力与叔丁基对羟基茴香醚之间无显著性差异,但均弱于维生素C.结论 新疆两色金鸡菊的EAE具有很强的抗脂质过氧化能力,同时具有一定清除亚硝酸盐和阻断亚硝胺形成的能力.     

茶多酚清除氧自由基及抑制脑脂质过氧化反应的体外试验

目的研究茶多酚对羟自由基（·ＯＨ）、超氧阴离子自由基（Ｏ·２）的清除作用及其对脂质过氧化的抑制作用。方法茶多酚与自由基发生体系或大鼠脑线粒体共浴后，比色法测定·ＯＨ、Ｏ·２及丙二醛生成量。结果茶多酚对Ｆｅｎｔｏｎ反应生成的·ＯＨ及黄嘌呤－黄嘌呤氧化酶系统产生的Ｏ·２具有较强的清除作用，ＩＣ５０分别为９１９．６ｍｇ·Ｌ－１和８３６ｍｇ·Ｌ－１。茶多酚对·ＯＨ诱导的离体大鼠脑线粒体产生的脂质过氧化有明显的抑制作用。结论茶多酚的抗脂质过氧化作用与其清除氧自由基作用有关     

Thymoquinone is a potent superoxide anion scavenger

The antioxidant and pro-oxidant effects of thymoquinone (TQ), a natural main constituent of the volatile oil of Nigella saliva seeds, and a synthetic structurally-related tert-butylhydroquinone (TBHQ), were examined in vitro. Both TQ and TBHQ efficiently inhibited iron-dependent microsomal lipid peroxidation in a concentration-dependent manner with median inhibitory concentration (IC50) values of 16.8 and 14.9 microM, respectively. TBHQ was stronger than TQ as a scavenger of 2,2'-diphenyl-p-picrylhydrazyl radical (DPPH) (IC50 = 5 microM, 200 times more active than TQ) and as a scavenger of hydroxyl radical (OH*) with an IC50 of 4.6 microM (approximately 10 times more active than TQ). TQ was more active than TBHQ as a superoxide anion scavenger with IC50 of 3.35 microM compared to 18.1 microM for TBHQ. Only TBHQ significantly promoted DNA damage in the bleomycin-Fe(III) system. The results suggest that both TQ and TBHQ have strong antioxidant potentials through scavenging ability of different free radicals. Moreover, the data indicate that TQ is acting mainly as a potent superoxide anion scavenger.     

Inhibitory effects of condensed tannins on angiotensin converting enzyme

Effects of condensed tannins isolated from Rhei Rhizoma on the activities of angiotensin converting enzyme (ACE) and various proteases were examined in vitro. Among the various condensed tannins tested, procyanidin B-5 3,3'-di-O-gallate and procyanidin C-1 3,3',3"-tri-O-gallate strongly inhibited the activity of ACE. The concentration of procyanidin B-5 3,3'-di-O-gallate required for 50% inhibition of ACE was 1.3 X 10(-6) M. The inhibition of ACE by condensed tannins was reversible and non-competitive, according to dialysis and to Dixon plots. However, over one hundred times the concentration was required to inhibit activities of other proteases such as trypsin, chymotrypsin, leucine aminopeptidase, carboxypeptidase A and urinary kallikrein. These results suggest that the inhibitory effects of condensed tannins on the activities of ACE are specific.     

Kinetic Characterization and Identification of the Enzymes Responsible for the Hepatic Biotransformation of Adinazolam and N-Desmethyladinazolam in Man

The kinetics of the N-demethylation of adinazolam to N-desmethyladinazolam (NDMAD), and of NDMAD to didesmethyladinazolam (DDMAD), were studied with human liver microsomes using substrate concentrations in the range 10–1000 μm . The specific cytochrome P450 (CYP) isoforms mediating the biotransformations were identified using microsomes containing specific recombinant CYP isozymes expressed in human lympho-blastoid cells, and by the use of CYP isoform-selective chemical inhibitors. Adinazolam was demethylated by human liver microsomes to NDMAD, and NDMAD was demethylated to DDMAD; the substrate concentrations, K_m, at which the reaction velocities were 50% of the maximum were 92 and 259 μm , respectively. Another metabolite of yet undetermined identity (U) was also formed from NDMAD (K_m 498 μm ). Adinazolam was demethylated by cDNA-expressed CYP 2C19 (K_m 39 μm ) and CYP 3A4 (K_m 83 μm ); no detectable activity was observed for CYPs 1A2, 2C9, 2D6 and 2E1. Ketoconazole, a relatively specific CYP 3A4 inhibitor, inhibited the reaction; the concentration resulting in 50% of maximum inhibition, IC50, was 0·15 μm and the inhibition constant, K_i, was < 0·04 μm in five of six livers tested. Troleandomycin, a specific inhibitor of CYP 3A4, inhibited adinazolam N-demethylation with an IC50 of 1·96 μm . The CYP 2C19-inhibitor omeprazole resulted in only partial inhibition (IC50 21 μm ) and sulphaphenazole, α-naphthoflavone, quinidine and diethyldithiocarbamate did not inhibit the reaction. NDMAD was demethylated by cDNA-expressed CYP 3A4 (K_m 220 μm , Hill number A 1·21), CYP 2C19 (K_m 187 μm , Hill number A 1·29) and CYP 2C9 (K_m 1068 μm ). Formation of U was catalysed by CYP 3A4 alone. Ketoconazole strongly inhibited NDMAD demethylation (IC50 0·14 μm ) and formation of U (IC50 < 0·1 μm ) whereas omeprazole and sulphaphenazole had no effect on reaction rates. These results show that CYP 3A4 is the primary hepatic CYP isoform mediating the N-demethylation of adinazolam and NDMAD. Co-administration of adinazolam with CYP 3A4 inhibitors such as ketoconazole or erythromycin might lead to reduced efficacy, since adinazolam by itself has relatively weak benzodiazepine agonist activity, with much of the pharmacological activity of adinazolam being attributable to its active metabolite NDMAD.     

内南五味子木脂素戈米辛J对肝线粒体膜脂质过氧化和超氧阴离子自由基的作用

目的　研究来自内南五味子的戈米辛J对脂质过氧化的影响和清除超氧阴离子自由基 (O·2 )的能力。方法　采用离体大鼠肝线粒体膜的脂质过氧化模型和黄嘌呤氧化酶 鲁米诺化学发光法。结果　戈米辛J象VitE一样能剂量依赖性抑制Fe2 + VitC和ADP/NADPH所致的脂质过氧化 ;戈米辛J的IC50 分别为 5 75 ( 95 %可信限 :5 42～ 6 11)和0 95 ( 0 14～ 6 5 4) μmol·L-1。VitE的IC50 分别为 74 8( 30 2～ 185 3)和 6 5 1( 0 13～ 319) μmol·L-1。戈米辛J抑制Fe2 + VitC和ADP/NADPH所致的脂质过氧化的作用比VitE的作用分别强 13倍和 6 8倍。戈米辛J也剂量依赖地抑制黄嘌呤 黄嘌呤氧化酶 鲁米诺化学发光 ,其抑制发光强度 5 0 %的浓度 (IC50 )为 2 18 2 2 μmol·L-1。结论　戈米辛J具有抑制OH·诱导的脂质过氧化和清除O·2 的作用     

几种香茶菜属二萜化合物对自由基导致线粒体损伤的保护作用

目的了解香茶菜属二萜类化合物冬凌草甲素（Ｏｒｉｄ）、腺花香茶素（Ａｄｅ）、黄花香茶菜素（Ｓｃｕｌ）是否具有抗氧化作用。方法用分光光度法测定脂质过氧化物丙二醛（ＭＤＡ）含量及线粒体肿胀度。用荧光分光光度法测定线粒体膜流动性。结果Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ４０,８０,１６０μｍｏｌ·Ｌ－１抑制铁－半胱氨酸（Ｆｅ２＋－Ｃｙｓ）引起的肝线粒体ＭＤＡ形成,并呈剂量依赖关系。Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ１６０μｍｏｌ·Ｌ－１抑制肝线粒体膜流动性下降（Ｐ值分别为２．２９７±０．０２２,０．３８９±０．００９,０．３８２±０．０１３,Ｆｅ２＋－Ｃｙｓ的Ｐ值为０．４２３±０．０１４）;Ａｄｅ１６０μｍｏｌ·Ｌ－１还可抑制脂质过氧化引起的肝线粒体肿胀。结论Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ可能通过抑制脂质过氧化而产生抗氧化作用     

三七中人参三醇甙对大鼠离体心脏缺血再灌注损伤及心律失常的保护作用

三七中人参三醇甙(PTS)5,50μg·ml~(-1)灌流对离体大鼠Langendorff心脏缺血再灌注所致心律失常具有明显的保护作用,可降低室颤发生率,并可保护心肌组织中超氧化物歧化酶的降低,PTS 50μg·ml~(-1)还可抑制心肌丙二醛的产生,对缺血再灌注所致心肌乳酸脱氩酶和磷酸肌酸激酶的漏出亦有明显的抑制作用。     

Antioxidant activity of two phloroglucinol derivatives from Dryopteris crassirhizoma

The rhizome of Dryopteris crassirhizoma NAKAI exhibited significant antioxidant activity, as assessed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity in vitro. Two phloroglucinol derivatives, flavaspidic acids PB (1) and AB (2), were isolated from the rhizome of D. crassirhizoma by a bioassay-guided fractionation. 1H-, 13C-NMR, and UV analysis were used to determine the structures. Furthermore, the two compounds were tested for their antioxidant activities, such as their DPPH radical scavenging, superoxide radical scavenging, and lipid peroxidation (LPO) inhibitory activities. Compounds 1 and 2 exhibited potent antioxidant activity against the LPO inhibitory test with IC(50) values of 12.9 and 13.1 microM, respectively, compared with alpha-tocopherol (IC(50); 15.6 microM) and butylated hydroxy anisole (BHA, IC(50); 10.8 microM), while the two compounds had a moderated effect on the DPPH radical scavenging activity (IC(50); 71.7, 76.3 microM) as well as superoxide radical scavenging activity (IC(50); 58.6, 64.4 microM). The potent activity of the flavaspidic acids (1, 2) on inhibiting LPO might be due to possible stabilization as a result of chelating with iron.     

化合物3,4,5-三羟基-N-[2-(4-羟基苯基)乙基]苯甲酰胺的抗氧化活性

目的对化合物3,4,5-三羟基-N-[2-(4-羟基苯基)乙基]苯甲酰胺(3,4,5-trihydroxy-N-[2-(4-hydroxyphenyl)ethyl]-benzamide,THHEB)的抗氧化活性进行研究。方法通过测定对有机自由基1,1-二苯基苦基苯肼(1,1-diphenyl-2-picrylhydrazyl,DPPH)的清除能力、6-羟基-2,5,7,8-四甲基苯并二氢吡喃-2-羧酸(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid,Trolox)当量抗氧化能力(trolox-equivalent antioxidant capacity assay,TEAC),测定超氧自由基的清除活性实验、脂质过氧化法以及羟基自由基诱导DNA损伤的方法评价THHEB的抗氧化活性。结果5种方法检测结果均显示,THHEB具有很强的清除自由基的活性。其中,THHEB对稳定自由基DPPH和超氧自由基的清除能力超过抗坏血酸的相应活性,其IC50值分别为22.8、2.5μmol.L-1。用TEAC方法测定THHEB总的抗氧化能力大约为0.6,也比L-抗坏血酸相应值高。脂质过氧化法测定的THHEB活性要弱于著名的抗氧化化合物2,6-二叔基对甲苯酚(butylated hydroxytoluene,BHT)。此外,非常小浓度比如4μmo.lL-1的THHEB对羟基自由基导致的pBR322 DNA链断裂具有显著的保护作用。结论THHEB具有很强的清除自由基的活性。     

马齿苋多糖的抗氧化活性研究

目的研究马齿苋多糖(POP)的抗氧化作用。方法采用体外实验研究POP对超氧阴离子、羟自由基、DPPH的清除作用以及对H2O2诱导的红细胞氧化溶血和大鼠肝匀浆脂质过氧化的保护作用。结果 POP对超氧阴离子和羟自由基具有良好的清除作用,IC50分别为4.29和1.97μg/mL,对有机自由基DPPH的作用很弱。POP对自发性脂质过氧化和H2O2诱导的脂质过氧化具有良好的保护作用,但对H2O2诱导的红细胞氧化溶血作用较弱。结论 POP具有显著的体外抗氧化活性。     

Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside

Three flavonoids, gnaphaliin, pinocembrin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their antioxidant and/or scavenger properties and in vivo in different models of inflammation. In vitro tests included lipid peroxidation in rat liver microsomes, superoxide radical generation in the xanthine/xanthine oxidase system and the reduction of the stable radical 1,1-diphenyl-2-pycryl-hydrazyl (DPPH). Acute inflammation was induced by application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to the mouse ear or by subcutaneous injection of phospholipase A(2) or serotonin in the mouse paw. Eczema provoked on the mouse ear by repeated administration of TPA was selected as a model of chronic inflammation. The flavonoids were assayed against sheep red blood cell-induced mouse paw oedema as a model of delayed-type hypersensitivity reaction. The most active compound, both in vitro and in vivo, was tiliroside. It significantly inhibited enzymatic and non-enzymatic lipid peroxidation (IC(50)=12.6 and 28 microM, respectively). It had scavenger properties (IC(50)=21.3 microM) and very potent antioxidant activity in the DPPH test (IC(50)=6 microM). In vivo, tiliroside significantly inhibited the mouse paw oedema induced by phospholipase A(2)(ED(50)=35.6 mg/kg) and the mouse ear inflammation induced by TPA (ED(50)=357 microg/ear). Pinocembrin was the only flavonoid that exhibited anti-inflammatory activity in the sheep red blood cell-induced delayed-type hypersensitivity reaction. However, only tiliroside significantly reduced the oedema and leukocyte infiltration induced by TPA. As in the case of other flavonoids, the anti-inflammatory activity of tiliroside could be based on its antioxidant properties, although other mechanisms are probably involved.     

Free radical scavenging and antiacetylcholinesterase activities of Origanum majorana L. essential oil

In the present study, Origanum majorana L. essential oil (EO) was analyzed by gas chromatography-mass spectrometry (GC-MS) and evaluated for free radical scavenging and anticholinesterase activities. GC-MS analysis revealed the presence of 4-terpineol (29.97%), γ-terpinene (15.40%), trans-sabinene hydrate (10.93), α-terpinene (6.86%), 3-cycolohexene-1-1 methanal,a,a4-trimethyl-,(S)-(CAS) (6.54%), and sabinene (3.91%) as main constituents. Origanum majorana L. EO exhibited concentration-dependent inhibitory effects on 2,2'-diphenylpicrylhydrazyl (DPPH(?)), hydroxyl radical, hydrogen peroxide, reducing power, and lipid peroxidation with IC(50) values of 58.67, 67.11, 91.25, 78.67, and 68.75 μg/mL, respectively; while the IC(50) values for the standard trolox were noted to be 23.95, 44.97, 51.30, 42.22, and 52.72 μg/mL, respectively. Interestingly, cholinesterase inhibitory activity was also found with IC(50) values of 36.40 μg/mL. We can conclude that the marjoram EO has a significant potential to be used as a natural antioxidant and anti-AChE.     

Comparative study of eight well-known polyphenolic antioxidants

Eight antioxidants from five different polyphenolic classes (cinnamic acids, benzoic acids, flavonoids, proanthocyanidins and stilbenes), and the water-soluble vitamin E derivative trolox were examined for their antioxidant activity in-vitro. In addition, the compounds were tested for their cytotoxicity on growing fibroblasts and their inhibition of the classical pathway of the complement system. Procyanidin C1 was shown to be a good scavenger of both DPPH(*) and HO(*), and a strong inhibitor of lipid peroxidation and the classical pathway of the complement system. Consequently, procyanidin C1 was classified as the most promising antioxidant in-vitro of all compounds tested. In contrast, genistein exhibited a very low antioxidant activity in both the lipid peroxidation and the DPPH(*) scavenging assay, a high cytotoxicity and a low complement-inhibiting activity.     

赛庚啶的抗脂质过氧化作用

赛庚啶(Cyp)对自氧化及自由基发生系统(FRGS)诱导离体大鼠心,肝,脑组织脂质过氧化作用均有明显的抑制效应,且对后者的抑制作用更为明显,其IC_(50)分别为2.56mmol·L~(-1),693,973μmol·L~(-1)和63,56,379μmol·L~(-1)Cyp对FRGS诱导离体大鼠心肌线粒体膜脂质过氧化作用也有一定的抑制作用,其IC_(50)为5.1mmol·L~(-1).结果提示Cyp的抗脂质过氧化作用与其清除氧自由基作用有关