Free Radical Scavenging Properties of Sulfinpyrazone

Sulfinpyrazone, a potent uricosuric drug, was tested in vitro for its scavenging action against oxygen free radicals. In this study, sulfinpyrazone was able to scavenge 1,1-diphenyl-2-picrylhydrazyl radical with IC 50 value of 29.82 &#119 g/ml compared to butylated hydroxytoluene (BHT, IC 50 value=20.15 &#119 g/ml) and Trolox (IC 50 value=16.01 &#119 g/ml). It was able to scavenge superoxide anion with IC 50 value of 27.72 &#119 g/ml compared to Trolox (IC 50 value=22.08 &#119 g/ml) and ascorbic acid (IC 50 value=14.65 &#119 g/ml). The hydroxyl radical scavenging activity of sulfinpyrazone is in a concentration-dependent fashion. In the range of concentrations used, sulfinpyrazone was not a scavenger toward H 2 O 2 . However, the intracellular H 2 O 2 -induced 2',7'-dichlorofluorescin diacetate (DCF-DA) fluorescence in HL-60 cells was significantly reduced by sulfinpyrazone during 30-60 min of incubation. Finally, phorbol-12-myristate-13-acetate induced-lucigenin chemiluminescence in whole blood was markedly inhibited by sulfinpyrazone. Our results suggest a new direction for the pharmacological actions of sulfinpyrazone in free radical scavenging properties.     

Antioxidant and radical scavenging properties of curcumin

Curcumin (diferuoyl methane) is a phenolic compound and a major component of Curcuma longa L. In the present paper, we determined the antioxidant activity of curcumin by employing various in vitro antioxidant assays such as 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH*) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging activity, total antioxidant activity determination by ferric thiocyanate, total reducing ability determination by the Fe(3+)-Fe(2+) transformation method, superoxide anion radical scavenging by the riboflavin/methionine/illuminate system, hydrogen peroxide scavenging and ferrous ions (Fe(2+)) chelating activities. Curcumin inhibited 97.3% lipid peroxidation of linoleic acid emulsion at 15 microg/mL concentration (20 mM). On the other hand, butylated hydroxyanisole (BHA, 123 mM), butylated hydroxytoluene (BHT, 102 mM), alpha-tocopherol (51 mM) and trolox (90 mM) as standard antioxidants indicated inhibition of 95.4, 99.7, 84.6 and 95.6% on peroxidation of linoleic acid emulsion at 45 microg/mL concentration, respectively. In addition, curcumin had an effective DPPH* scavenging, ABTS*(+) scavenging, DMPD*(+) scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe(3+)) reducing power and ferrous ions (Fe(2+)) chelating activities. Also, BHA, BHT, alpha-tocopherol and trolox, were used as the reference antioxidant and radical scavenger compounds. According to the present study, curcumin can be used in the pharmacological and food industry because of these properties.     

Basic Principles of Reactivity in Free Radical Chemistry

This review is concerned with an overall survey of reactivity in free radical chemistry. A concise classification is given of elementary reaction steps which can be combined in different ways to account for overall chemical transformations: radical forming reactions, radical transformations, and radical destroying reactions. From this is derived the concept of the chain reaction which leads on to an up-to-date theory for understanding reactivity in free radical processes. Finally, a few aspects of autoxidation are discussed.     

Basic Principles of Reactivity in Free Radical Chemistry

This review is concerned with an overall survey of reactivity in free radical chemistry. A concise classification is given of elementary reaction steps which can be combined in different ways to account for overall chemical transformations: radical forming reactions, radical transformations, and radical destroying reactions. From this is derived the concept of the chain reaction which leads on to an up-to-date theory for understanding reactivity in free radical processes. Finally, a few aspects of autoxidation are discussed.     

Free radical scavenging and antiproliferative properties of Biginelli adducts

A series of Biginelli adducts bearing different substituents at C-4 position were synthesized by using p-sulfonic acid calix[4]arene as a catalyst. The in vitro potential to scavenge reactive nitrogen/oxygen species (RNS and ROS) and the ability to inhibit cancer cells growth were then investigated. Four adducts were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (RNS) and/or superoxide anion (ROS) radicals. The antiproliferative activity against cancer cells was disclosed for the first time for 16 monastrol analogs. The capacity of all compounds to inhibit cancer cells growth was dependent on the histological origin of cells, except for BA24, which was highly active against all cell lines. BA20 and BA33 were as potent as the reference drug doxorubicin against adriamycin-resistant ovarian and prostate cancer cells, respectively. These results highlight some monastrol analogs as lead compounds for the design of new free radical scavengers and anticancer agents.     

Free radical scavenging behavior of folic acid: evidence for possible antioxidant activity

The free radical scavenging properties and possible antioxidant activity of folic acid are reported. Pulse radiolysis technique is employed to study the one-electron oxidation of folic acid in homogeneous aqueous solution. The radicals used for this study are CCl₃O₂^•, N₃^•, SO₄^•−, Br₂^•−, √OH, and O^•−. All these radicals react with folic acid under ambient condition at an almost diffusion-controlled rate producing two types of transients. The first transient absorption maximum is around 430 nm, which decays, and a simultaneous growth at around 390 nm is observed. Considering the chemical structure of folic acid, the absorption maximum at 430 nm has been assigned to a phenoxyl radical. The latter one is proposed to be a delocalized molecular radical. A permanent product has been observed in the oxidation of folic acid with CCl₃O₂^• and N₃^• radicals, with a broad absorption band around 370–400 nm. The bimolecular rate constants for all the radical-induced oxidation reactions of folic acid have been measured. Folic acid is seen to scavenge these radicals very efficiently. In the reaction of thiyl radicals with folic acid, it has been observed that folic acid can not only scavenge thiyl radicals but can also repair these thiols at physiological pH. While carrying out the lipid peroxidation study, in spite of the fact that folic acid is considerably soluble in water, we observed a significant inhibition property in microsomal lipid peroxidation. A suitable mechanism for oxidation of folic acid and repair of thiyl radicals by folic acid has been proposed.     

A Novel Interleukin Stimulating Free Radical Production by Granulocytes

Polymorphonuclear granulocytes (PMN) are potent producers of free oxygen-derived radicals. Since other granulocyte functions are affected by interleukins, we investigated whether free-radical production can be initiated by a similar mediator. For estimation of free radical production, SOD-inhibitable lucigenin-dependent chemiluminescence and SOD-inhibitable cytochrome C reduction were used. As a source of interleukins, serum-free 24 h culture supernatants of human mononuclear cells (MNC) stimulated with bacterial lipopolysaccharide were prepared. Addition of such supernatants to PMN caused stimulation of sod-inhibitable chemiluminescence and superoxide production. Studies with separated MNC showed that monocytes were the cellular source of the activity. Biochemically, this activity of the supernatants was due to a heat-labile glycoprotein with a MW of approx. 60KDa. This mediator, termed granulocyte chemiluminescence inducer (GCI), appears to be distinct from interleukin 1 (a and j?) and interferon (a and y). In conclusion we describe a novel monokine, granulocyte chemiluminescence inducer (GCI), which initiates granulocyte free radical production. This interaction of monocytes and granulocytes may also in vivo constitute a new and potent pathway leading to stimulation of free oxygen production by granulocytes.     

Free radical scavenging and cytotoxic properties in the ellipticine series

In the series of cytotoxic intercalating compounds derived from ellipticine, we tried to correlate free radical scavenging properties with cytotoxic activities. Scavenging properties were determined in vitro on two experimental models: a) antioxidant activity of the drugs during the autoxidation of methyl linolenate induced by azo-bis-isobutyronitrile; this activity was measured either by the initial rate ratios in the presence and in the absence of the drug or by the length of the inhibition period of the reaction in the presence of the drug and b) ability to reduce DPPH free radicals. Cytotoxic properties were expressed by ID50 the dose which reduces by 50% the L 1210 cell growth rate as compared to controls after 48 h. It appears that antioxidant activity and reduction of DPPH both require the presence of a free OH group on the ellipticine ring. A good correlation is observed between cytotoxicity and antioxidant activity of the hydroxylated derivatives; minor structural modifications which result in a loss of cytotoxic activity also result in a loss of antioxidant properties. No such correlation is observed with DPPH reducing properties of ellipticine derivatives.     

A Novel Interleukin Stimulating Free Radical Production by Granulocytes

Polymorphonuclear granulocytes (PMN) are potent producers of free oxygen-derived radicals. Since other granulocyte functions are affected by interleukins, we investigated whether free-radical production can be initiated by a similar mediator. For estimation of free radical production, SOD-inhibitable lucigenin-dependent chemiluminescence and SOD-inhibitable cytochrome C reduction were used. As a source of interleukins, serum-free 24 h culture supernatants of human mononuclear cells (MNC) stimulated with bacterial lipopolysaccharide were prepared. Addition of such supernatants to PMN caused stimulation of sod-inhibitable chemiluminescence and superoxide production. Studies with separated MNC showed that monocytes were the cellular source of the activity. Biochemically, this activity of the supernatants was due to a heat-labile glycoprotein with a MW of approx. 60KDa. This mediator, termed granulocyte chemiluminescence inducer (GCI), appears to be distinct from interleukin 1 (a and j?) and interferon (a and y). In conclusion we describe a novel monokine, granulocyte chemiluminescence inducer (GCI), which initiates granulocyte free radical production. This interaction of monocytes and granulocytes may also in vivo constitute a new and potent pathway leading to stimulation of free oxygen production by granulocytes.     

自由基稳衡性动态

虽然自由基具有很活泼的化学性质 ,但在需氧生物的进化中却一直保持着自由基稳衡性动态的特征 ,体现于某些生物程序 ,包括 :在生理情况下履行其生理作用 ;维持其产生与清除于接近平衡 ;余剩的自由基引发生物大分子的损伤及其损伤可被修复。营养素及其代谢物和“必需”抗氧化剂对自由基稳衡态的正常维持起着关键性作用。谷胱甘肽及其它生物物质的稳衡性动态与自由基稳衡性动态有着协调的相互关系。在各种生活条件下 ,不同年龄的健康人体内自由基稳衡性动态应维持良好 ,以预防衰老前氧化应激与氧化损伤的发生     

Free radical scavenging activity of propolis

We investigated the radical scavenging activity of propolis by ESR spectroscopy using spin trapping method. In addition, we examined the influence of a diet of 2% propolis on mice under oxidative stress. At low concentrations, the methanolic extract of propolis exhibited strong scavenging activity in vitro towards both the superoxide anion radical, generated by the hypoxanthine-xanthine oxidase reaction, and the NO radical, generated from the mixture of NOC-7 (NO generator) and carboxy-PTIO (spin trapping agent). An inhibitory effect of propolis on lipid peroxidation in vivo was observed, as determined by measurement of thiobarbituric acid-reactive substances in mouse liver homogenate. The level of vitamin C in the brain of mice under oxidative stress significantly increased compared with control mice under atmosphere, which was not observed in the mice given 2% propolis. The level of alpha-tocopherol in the brain of mice given 2% propolis significantly increased compared with control mice under atmosphere, which was not observed in mice under oxidative stress. SOD activity in the brain and plasma of mice given 2% propolis significantly decreased under atmosphere and oxidative stress compared with control mice. These results suggest that propolis possesses potent antioxidant activity in vitro and in vivo.     

Free Radical Participation in Bacterial Bioluminescence

The metastable intermediate II produced on reaction of bacterial luciferase with reduced flavin mononucleotide and O₂, reacts with any of several stable free radicals to produce bioluminescence. The bioluminescence spectrum is very similar to that from the well-studied intermediate II and aldehyde reaction, and the number of photons per luciferase molecule reacted is at least 40% of the aldehyde reaction.     

Free radical scavenging potential of L-proline: evidence from in vitro assays

Summary. An assessment of the potential of proline to scavenge free radicals was made in a couple of in vitro assay systems, namely graft co-polymerization and autooxidation of pyrogallol. Both these assays are essentially dependent upon free radical mechanisms. Graft co-polymerization involved a ceric (Ce⁴⁺) ion- or γ-radiation-induced grafting of methyl acrylate (MA) onto a cellulose backbone. The degree of grafting, measured gravimetrically, was taken as a measure of free radical generation. The γ-radiation-dependent grafting was far greater than that due to Ce⁴⁺ ions. Inclusion of proline in the assay, irrespective of the initiator used, led to suppression of grafting in a concentration-dependent manner indicating the ability of proline to scavenge free radicals. The γ-radiation-dependent grafting was also suppressed by hydroquinone and glutathione but not by ascorbate, glycine and spermine. In contrast to graft co-polymerization, proline did not inhibit the autooxidation of pyrogallol, a reaction involving superoxide radical generation. A subset of data constitutes an evidence for the ability of proline to scavenge free radicals in vitro. It is implied by extension that free proline, known to accumulate in plant tissues during abiotic stresses, would contribute to scavenging of surplus free radicals produced under a variety of abiotic stresses. Authors’ address: Shanti S. Sharma, Department of Biosciences, Himachal Pradesh University, Shimla 171 005, India     

自由基、营养、天然抗氧化剂与衰老

影响衰老的因素很多,其中主要有遗传基因、饮食营养、生活方式、运动多少、心理状态、医疗条件及环境因素等。其中饮食营养是非常重要的因素,而且是可以控制的因素。研究证明,营养不良和营养过剩都会影响健康和寿命,而健康和延长寿命最有效的方法是限食(限能)。最近,美国和英国的权威杂志《Science》和《Nature》发表研究文章表明,节食,以及一些自由基清除剂,如小分子多酚类物质白藜芦醇,可以启动长寿基因SIRI1,抑制肿瘤基因p53,阻断细胞凋亡,延缓衰老和延长寿命。早在1955年,Dr. Harman发表的“衰老的自由基理论”就提出,体内产生过多自由基是引起衰老的重要因素,保持体内自由基和抗氧化剂的平衡可以延缓衰老。我们的实验还证明,天然抗氧化剂茶多酚可延长果蝇的寿命,使果蝇匀浆中的超氧化物歧化酶(superoxide dismutase,SOD)活性增加,脂质过氧化水平降低,改善高脂引起的果蝇寿命缩短、SOD活性降低以及脂质过氧化水平的升高。作者最近的实验还证明,茶多酚可以防止氧化应激引起的线虫寿命的缩短,还可以预防和治疗6-OHDA引起的大鼠帕金森氏综合症,山楂黄酮可以预防和治疗蒙古沙鼠缺血引起的中风,大豆异黄酮和尼古丁可以预防和治疗转基因线虫和小鼠老年痴呆症。饮食营养和天然抗氧化剂研究的进展将对人类健康和延缓衰老,提供新的线索并做出重大贡献。     

Free radical scavenging efficiency of Nano-Se in vitro

In this study, we showed that smaller size particles of Nano-Se have better scavenging effects on the following free radicals: carbon-centered free radicals (R*) generated from 2,2'-azo-bis-(2-amidinopropane) hydrochloride (AAPH), the relatively stable free radical 1,1-diphenyl-2-picryhydrazyl (DPPH), the superoxide anion (O2*-) generated from the xanthine/xanthine oxidase (X/XO) system, singlet oxygen (1O2) generated by irradiated hemoporphyrin. Furthermore, the three sizes of Nano-Se studied also show protective effects against the oxidation of DNA. The three samples all have potential size-dependent characteristics on scavenging the free radicals. Although in this study we regarded Nano-Se as a whole without considering interactions between BSA and the red selenium nano-particles, there is the possibility that the apparent free radical scavenging effects may be partially contributed by such interactions.     

Synthesis and characterization of CAPE derivatives as xanthine oxidase inhibitors with radical scavenging properties

Inhibitors of the enzyme xanthine oxidase (XO) with radical scavenging properties hold promise as novel agents against reperfusion injuries after ischemic events. By suppressing the formation of damaging reactive oxygen species (ROS) by XO or scavenging ROS from other sources, these compounds may prevent a buildup of ROS in the aftermath of a heart attack or stroke. To combine these two properties in a single molecule, we synthesized and characterized the non-purine XO inhibitor caffeic acid phenethylester (CAPE) and 19 derivatives using a convenient microwave-assisted Knoevenagel condensation protocol. Varying systematically the number and positions of the hydroxyl groups at the two phenyl rings, we derived structure-activity relationships based on experimentally determined XO inhibition data. Molecular docking suggested that critical enzyme/inhibitor interactions involved π-π interactions between the phenolic inhibitor ring and Tyr914, hydrogen bonds between inhibitor hydroxyl groups and Glu802, and hydrophobic interactions between the CAPE phenyl ring and non-polar residues located at the entrance of the binding site. To effectively scavenge the stable radical DPPH, two hydroxyl groups in 1,2- or 1,4-position at the phenyl ring were required. Among all compounds tested, E-phenyl 3-(3,4-dihydroxyphenyl)acrylate, a CAPE analog without the ethyl tether, showed the most promising properties.     

Free Radical Formation from the Antineoplastic Agent VP 16-213

Free radical formation from VP 16-213 was studied by ESR spectroscopy. Incubation of VP 16-213 with the one-electron oxidators persulphate-ferrous, myeloperoxidase (MPO)/hydrogen peroxide and horseradish peroxidase (HRP)/hydrogen peroxide readily led to the formation of a free radical. The ESR spectra obtained in the last two cases, were in perfect accord with that of a product obtained by electrochemical oxidation of VP 16-213 at +550 mV. The half-life of the free radical in 1 mM Tris (pH 7.4), 0.1 MNaClat 20°C, was 257 ± 4 s. The signal recorded on incubation with HRP/H₂O₂ or MPO/H₂O₂ did not disappear on addition of 0.3 - 1.2 mg/ml microsomal protein. From incubations with rat liver microsomes in the presence of NADPH, no ESR signals were obtained.     

活性氧自由基诱发的胆红素聚合、聚集及稳定自由基的形成

 为了深入了解胆红色素类结石形成的触发机制,我们研究了活性氧自由基与胆红素的作用。结果表明:·O_2和·OH均可诱发胆红素聚合和聚集,井使胆红素转变成稳定的自由基,从而引起脂质过氧化和透明质酸分子降解。经自由基处理的胆红素溶解度减小,粒度分布趋向颗粒变大.根据以上事实,重点讨论了自由基触发的胆色素类结石的致病过程。     

Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies

Embelin (from Embelia ribes) is a component of herbal drugs and possess wide range of medicinal properties. These properties may be, in part, due to scavenging of oxidizing free radicals. In this context, free radical scavenging reactions and antioxidant activity of embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) have been studied. It has been found to scavenge DPPH radical and inhibit hydroxyl radical induced deoxyribose degradation. It has been also found to inhibit lipid peroxidation and restore impaired Mn-superoxide dismutase in rat liver mitochondria. Further, kinetics and mechanism of the reactions of embelin with hydroxyl, one-electron oxidizing, organo-haloperoxyl and thiyl radicals have been studied using nanosecond pulse radiolysis technique. Its redox potential has been also evaluated with cyclic voltammetry. These studies suggest that embelin can act as a competitive antioxidant in physiological conditions.     

Free Radical Formation from the Antineoplastic Agent VP 16-213

Free radical formation from VP 16-213 was studied by ESR spectroscopy. Incubation of VP 16-213 with the one-electron oxidators persulphate-ferrous, myeloperoxidase (MPO)/hydrogen peroxide and horseradish peroxidase (HRP)/hydrogen peroxide readily led to the formation of a free radical. The ESR spectra obtained in the last two cases, were in perfect accord with that of a product obtained by electrochemical oxidation of VP 16-213 at +550 mV. The half-life of the free radical in 1 mM Tris (pH 7.4), 0.1 MNaClat 20°C, was 257 ± 4 s. The signal recorded on incubation with HRP/H₂O₂ or MPO/H₂O₂ did not disappear on addition of 0.3 - 1.2 mg/ml microsomal protein. From incubations with rat liver microsomes in the presence of NADPH, no ESR signals were obtained.