Hydroxyl radical scavenging reactivity of proton pump inhibitors

In addition to the established control of acid secretion of the class of proton pump inhibitors (PPI) reactivity from the pyridyl methyl sulphinyl benzimidazole type a second independent anti-inflammatory reactivity was observed in vitro. This inhibitory reactivity was clearly noticed using three different assays where the aggressive hydroxyl radicals were successfully trapped in a concentration dependent manner. There is unequivocal evidence that the proton pump inhibitors having the sulphoxide group are able to scavenge hydroxyl radicals which are generated during a Fenton reaction. By way of contrast, the corresponding thioethers were substantially less active. No detectable effect was seen in the superoxide radical scavenging system. In conclusion, pantoprazole as well as the other proton pump inhibitors have a pronounced inhibitory reactivity towards hydroxyl radicals.     

Hydroxyl radical scavenging mechanism of human erythrocytes by quercetin-germanium (IV) complex

Quercetin is a popular flavonoid in plant foods, herbs, and dietary supplement. Germanium, a kind of trace elements, can enhance the body immunity. This study investigated the hydroxyl-radical-scavenging mechanism of the quercertin-germanium (IV) (Qu-Ge) complex to human erythrocytes, especially the effects on ultrastructure and mechanical properties of cell membrane, plasma membrane potential and intracellular free Ca(2+) concentration. Results showed that QuGe(2), a kind of the Qu-Ge complex, could reduce the oxidative damage of erythrocytes, change the cell-surface morphology, and partly recover the disruption of plasma membrane potential and intracellular free Ca(2+) level. Atomic force microscopy (AFM) was used to characterize the changes of the cell morphology, cell-membrane ultrastructure and biophysical properties at nanoscalar level. QuGe(2) has triggered the antioxidative factor to inhibit cellular damage. These results can improve the understanding of hydroxyl-radical-scavenging mechanism of human erythrocytes induced by the Qu-Ge complex, which can be potentially developed as a new antioxidant for treatment of oxidative damage.     

The iron-binding and hydroxyl radical scavenging action of anti-inflammatory drugs

1. Hydroxyl radicals (.OH) are thought to be generated at sites of inflammation and to contribute to tissue damage. All anti-inflammatory drugs tested were able to scavenge .OH generated in free solution at almost diffusion-controlled rates (rate constants about 10(10)M-1s-1). 2. Much .OH generation in vivo occurs at specific sites, where bound metal ions (such as Fe2+) react with H2O2 to produce .OH that immediately attacks the site. Only .OH scavengers that have sufficient metal-binding ability to withdraw metal ions from this site can protect against site-specific damage. 3. All anti-inflammatory drugs tested were able to protect against site-specific damage by .OH in a simple model system in vitro. Penicillamine, diclofenac sodium, piroxicam, azathioprine, primaquine, chloroquine and hydroxychloroquine were especially effective. 4. The ability of an anti-inflammatory drug to protect against .OH formation in vivo depends not only on its rate constant for reaction with .OH, but also on its metal-binding ability and on the geometry and redox potential of any metal complex formed.     

Hydroxyl radical scavenging by ethyl gallate and related compounds: a method for rapid evaluation

Ethyl gallate and two related compounds, ethyl 4-hydroxybenzoate and ethyl 3,4-dihydroxybenzoate were evaluated as hydroxyl radical scavengers in a model system using dequalinium chloride and hydrogen peroxide irradiated with simulated sunlight to generate the radicals. All of the compounds showed some hydroxyl radical scavenging properties, with ethyl 3,4-dihydroxybenzoate being the most active under the conditions of test. The molecular implications of these results are considered. The potential radical scavengers were assessed individually for their reaction with photogenerated hydroxyl radicals and the results are discussed. The potential applications of this method for evaluating potential preservatives are also discussed.     

Hydroxyl and hydroperoxy radical scavenging by copper(II) chelates related to non-steroidal anti-inflammatory drugs

Solutions of dequalinium chloride with and without added hydrogen peroxide were irradiated in buffer solutions with simulated sunlight at 23 ± 1°C. The photodegradation of dequalinium chloride solution and hydrogen peroxide in buffer at pH 7.0 and 10.7 with the copper(II) chelates of ethyl N-substituted 4-hydroxy-5-oxo-3-pyrroline-3-carboxylates and 3,5-diisopropylsalicylic acid showed that only the copper(II) chelate of the latter scavenged hydroxyl radicals at pH 7.0. All the compounds tested showed hydroxyl radical scavenging effects at pH 10.7 and were scavengers for the hydroperoxy radical at pH 7.0. The structure-activity relationships in the compounds tested are discussed.     

珠芽蓼清除羟自由基作用研究

目的为了解珠芽蓼根茎作为蝙蝠蛾幼虫食物的生理作用,研究它的提取物对羟自由基的清除能力。方法采用邻二氮菲—Fe2+氧化法检测珠芽蓼根茎的提取物对H2O2/Fe2+体系产生的羟自由基的清除作用。结果珠芽蓼根茎蒸馏水提取物和丙酮提取物均对羟自由基有清除作用,其中丙酮提取物的作用最强。结论珠芽蓼根茎具有明显的清除羟自由基作用,其活性主要来自丙酮提取物部分。     

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。     

Hydroxyl radical formation by dithranol

Ethene formation from 2-keto-thiomethyl-butyric acid (KMBA) was used to measure hydroxyl radical generation from the antipsoriatic drug dithranol in phosphate buffer pH 7.8. Because the singlet oxygen (1O2) sensitizer, rose bengale, showed enlarged production of ethene when irradiated in the presence of KMBA, experiments were performed in the dark in order to avoid 1O2 production by dithranol. KMBA was converted to ethene by dithranol under aerobic conditions, whereas ethene formation was negligible in the absence of oxygen. Addition of catalytic amounts of FeCl3 resulted in increased ethene formation, indicating the catalysis of a superoxide-driven Fenton-reaction. O2- - and .OH-scavengers such as rutin, catechin, dimethyl sulfoxide, mannitol, ethanol, sodium salicylate and propyl gallate as well as catalase and superoxide dismutase inhibited ethene formation.     

Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation

Inhibitory effects of flavonoids rutin and quercetin on ferrous ion-dependent lipid peroxidation of lecithin liposomes and NADPH- and CCl4-dependent lipid peroxidation in rat liver microsomes were studied to elucidate the chelating and free radical scavenging activities of these compounds. The interaction of rutin with superoxide ion and ferrous ions and the reaction of quercetin with lipid peroxy radicals were also studied. Both flavonoids were significantly more effective inhibitors of iron ion-dependent lipid peroxidation systems due to chelating iron ions with the formation of inert iron complexes unable to initiate lipid peroxidation. At the same time, iron complexes of flavonoids retained their free radical scavenging activities. The chelating mechanism of inhibition was more important for rutin than for quercetin. The mutual effect of rutin and ascorbic acid on non-enzymatic lipid peroxidation was also studied. It was concluded that rutin and quercetin are able to suppress free radical processes at three stages: the formation of superoxide ion, the generation of hydroxyl (or cryptohydroxyl) radicals in the Fenton reaction and the formation of lipid peroxy radicals.     

Free radical scavenging potential of Saussarea costus

Saussurea costus (Falc.) Lipschitz from the family Asteraceae is an important medicinal drug, the roots of which are widely used in folk medicine. The antioxidant activity of the plant has been studied using its ability to scavenge DPPH, nitric oxide, superoxide radicals along with its ability to inhibit lipid peroxidation and GSH oxidation. The 1 mg mL(-1) extract had antioxidant activity with 85.2% reduction of DPPH and a 72.7% decrease in lipid peroxidation. It showed maximum inhibition of superoxide radical of 66.0%, and 58.4% inhibition of nitric oxide formation. The concentration of chlorogenic acid was 0.027% in the extract of S. costus. Thus, the therapeutic activity of the plant may be due to its antioxidant activity, probably as a result of the presence of chlorogenic acid.     

Free radical scavenging properties of pyrimidine derivatives

Free radicals are well known for playing a dual role in our body- deleterious as well as beneficial. It includes a metabolic pathway for its generation. Oxidative stress in our body occurs due to excessive generation of free radicals and reduced level of antioxidants, but at low concentrations, these radicals help to perform normal physiological functions of the body. Scientific evidence suggests that antioxidants reduce the risk for chronic diseases including cancer and heart disease. This review shows current tendency in the pyrimidine synthesis and reveals the pyrimidine core to be a very potent moiety which can be a rich source for the synthesis of new compounds having desirable antioxidant activity.     

Hydroxysafflor yellow A inhibits rat brain mitochondrial permeability transition pores by a free radical scavenging action

Hydroxysafflor yellow A (HSYA), the major and most active antioxidant from Carthamus tinctorius L., has been clinically prescribed in China to treat patients with cerebral ischemia, but the detailed mechanism is not known. This study examines the effect of HSYA on mitochondrial permeability transition pores (mtPTP) in the rat brain. HSYA at 10-80 micromol.l(-1) inhibited Ca(2+)- and H(2)O(2)-induced swelling of mitochondria isolated from rat brains. The addition of Ca(2+) generated reactive oxygen species (ROS) in isolated mitochondria. HSYA (10-80 micromol.l(-1)) inhibited Ca(2+)-induced generation of ROS. At the same time, HSYA significantly improved mitochondrial energy metabolism, enhanced ATP levels and the respiratory control ratio. These results suggest that HSYA inhibits the opening of mtPTP by a free radical scavenging action in the brain, and this may contribute to the neuroprotective effect of HSYA.     

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。     

Mode of action of poly(vinylpyridine-N-oxide) in preventing silicosis: effective scavenging of carbonate anion radical

Small particles of crystalline silicon dioxide (crystallites) are exceptionally toxic. Inhalation of quartz crystallites causes silicosis, a devastating lung disease afflicting miners, particularly coal and stone workers. Poly(vinylpyridine-N-oxide)s (PVPNOs) have been applied in the prevention and treatment of silicosis, but their mode of action has been obscure. Recently, the sites of inducible *NO synthase activation and of nitrotyrosine formation were associated anatomically with the pathological quartz particle-caused lesions in the lungs. It has been suggested that the *NO formed combines rapidly with O2*- to yield ONOO-, a potential mediator of lung injury following silica exposure. Here, we show that PVPNOs do not react with peroxynitrite but scavenge exceptionally rapidly CO3*- radicals, which are produced in the decomposition of ONOO- in bicarbonate solutions. The rate constant for the reaction of CO3*- with PVPNO was found to be independent of the type and size of PVPNO, i.e., k = (1.9 +/- 0.2) x 10(5) M(-1) s(-1) per monomer. In contrast, the rate constant for the reaction of CO3*- with the small molecule 4-methylpyridine N-oxide did not exceed 1 x 10(4) M(-1) s(-1). The underlying reason for the difference is that, in the dissolved polymeric PVPNOs, the electrostatic repulsion between the N-oxide zwitterions destabilizes them, increasing dramatically their pKa. The protonated N-oxides at physiological pH have abstractable hydrogen atoms and are expected to react rapidly with CO3*-, just as cyclic hydroxylamines do. It is also shown that PVPNO inhibits tyrosine nitration by peroxynitrite at pH 7.6 in the presence of excess of CO2 in a concentration-dependent manner. Hence, binding of PVPNO to the quartz particles and eliminating CO3*- could prevent the killing of macrophages, the associated release of macrophage-recruiting cytokines, and the amplification of the local concentration of *NO by the recruited macrophages. The latter causes necrosis of the macrophage-infiltrated lung tissue and, upon repair of the necrotic lesion, results in the growth of the dysfunctional fibrotic tissue, which is the hallmark of silicosis.     

Synthesis and radical scavenging of novel magnolol derivatives

We have investigated the developdment of potential antioxidants based on magnolol, a naturally occurring biphenolic obtained from the bark of Magnolia officinalis. A series of aminomethylated derivatives of magnolol were synthesized under the aromatic Mannich reaction. In-vitro testing for diphenyl-p-picrylhydrazyl (DPPH) scavenging and chemiluminescence assays in whole cell models revealed that the pyrrolidyl-containing magnolols (2b (5,5'-diallyl-3-(pyrrolidin-1-ylmethyl)-biphenyl-2,2'-diol), 3a (5,5'-diallyl-3,3'-bis-(pyrrolidin-1-ylmethyl)-biphenyl-2,2'-diol) and 4c (5,5'-diallyl-3-(morphorin-4-ylmethyl)-3'-(pyrrolidin-1-ylmethyl)-biphenyl-2,2'-diol)) displayed promising free radical scavenging effects as compared with magnolol. The results from compound 4c indicated that the naturally occurring component was suitable to be a lead compound toward promising antioxidants.     

杨树芽提取物清除DPPH自由基的作用

目的对杨树芽进行初步提取分离,测定其总黄酮含量和抗氧化活性。方法通过超声辅助提取杨树芽中有效成分,以抗坏血酸、生育酚和芦丁为对照品,采用DPPH法测定其自由基清除作用。结果超声辅助提取的杨树芽提取物中总黄酮含量为14.4%,浓度为0.05 g.L-1时,清除自由基能力大于芦丁和生育酚,浓度提高后略低于生育酚,高于芦丁,且清除能力随浓度提高而提高。结论杨树芽提取物中总黄酮含量较高,并有较强的抗氧化活性。     

植物活性多糖抗癌活性的研究——抗自由基作用

目的研究当归、鬼臼、黄芪和猫人参多糖对羟自由基的清除作用。方法采用分光光度法测定羟自由基清除率。结果半数抑制浓度(IC50)分别为当归0.4040g/L、鬼臼0.1021g/L、黄芪0.08782g/L和猫人参0.4913g/L。结论4种多糖对羟自由基的清除能力大小依次为黄芪>鬼臼>当归>猫人参,一定浓度范围内清除作用与多糖浓度具有正相关性。