1-1-diphenyl-2-picrylhydrazyl and 2-2--azobis(2-amidinopropane)

Phenolamines and flavonoids are two important components in bee pollen. There are many reports on the bioactivity of flavonoids in bee pollen, but few on phenolamines. This study aims to separate and characterize the flavonoids and phenolamines from rape bee pollen, and compare their antioxidant activities and protective effects against oxidative stress. The rape bee pollen was separated to obtain 35% and 50% fractions, which were characterized by HPLC-ESI-QTOF-MS/MS. The results showed that the compounds in 35% fraction were quercetin and kaempferol glycosides, while the compounds in 50% fraction were phenolamines, including di-p-coumaroyl spermidine, p-coumaroyl caffeoyl hydroxyferuloyl spermine, di-p-coumaroyl hydroxyferuloyl spermine, and tri-p-coumaroyl spermidine. The antioxidant activities of phenolamines and flavonoids were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays. It was found that the antioxidant activity of phenolamines was significantly higher than that of flavonoids. Moreover, phenolamines showed better protective effects than flavonoids on HepG2 cells injured by AAPH. Furthermore, phenolamines could significantly reduce the reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and increase the superoxide dismutase (SOD) and glutathione (GSH) levels. This study lays a foundation for the further understanding of phenolamines in rape bee pollen.

Topics: Alanine Transaminase; Amidines; Animals; Antioxidants; Aspartate Aminotransferases; Bees; Benzothiazoles; Biphenyl Compounds; Gene Expression; Glutathione; Glycosides; Hep G2 Cells; Humans; Kaempferols; Oxidants; Oxidative Stress; Picrates; Plant Extracts; Pollen; Quercetin; Reactive Oxygen Species; Spermidine; Spermine; Sulfonic Acids; Superoxide Dismutase

We had observed in our previous study that the active fucoidan (JHCF4), isolated from the crude fucoidan in acid-processed Hizikia fusiforme, possessed an anticancer effect. In this study, the antioxidant effect of JHCF4 was evaluated. Among the fractions, JHCF4 showed the highest scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH), alkyl, and hydroxyl radicals, as well as protective effect against reactive oxygen species (ROS) in 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-treated Vero cells. Furthermore, JHCF4 showed a protective activity against AAPH-induced apoptosis, as observed by nuclear staining with Hoechst 33342. Our results showed that JHCF4 can up-regulate Bcl-xL, down-regulate Bax and cleave caspase-3 with increased concentrations in AAPH-induced Vero cells. JHCF4 induced anti-apoptosis via a mitochondria-mediated pathway. Additionally, JHCF4 was selected for further in vivo screening in a zebrafish model, which markedly decreased ROS generation and lipid peroxidation. Thus, JHCF4 showed a potential protective activity against AAPH-induced ROS both in vitro and in the zebrafish model.

Topics: Amidines; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Biphenyl Compounds; Caspase 3; Cell Line; Chlorocebus aethiops; Down-Regulation; Lipid Peroxidation; Oxidative Stress; Picrates; Polysaccharides; Protective Agents; Reactive Oxygen Species; Sargassum; Stilbestrols; Up-Regulation; Vero Cells; Zebrafish

In this work six PBN-related indanonitrones 1-6 have been designed, synthesized, and their neuroprotection capacity tested in vitro, under OGD conditions, in SH-SY5Y human neuroblastoma cell cultures. As a result, we have identified indanonitrones 1, 3 and 4 (EC

Topics: Amidines; Antioxidants; Biphenyl Compounds; Cell Proliferation; Cell Survival; Cyclic N-Oxides; Dose-Response Relationship, Drug; Humans; Indans; Lipid Peroxidation; Molecular Structure; Neuroprotective Agents; Nitrogen Oxides; Picrates; Structure-Activity Relationship; Tumor Cells, Cultured

Topics: Amidines; Animals; Ascorbic Acid; Benzhydryl Compounds; Biphenyl Compounds; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Chromans; Erythrocytes; Free Radical Scavengers; Hydrazines; Hydrogen Peroxide; Imidazolines; Nitric Oxide; Picrates; Rats; Structure-Activity Relationship

A series of new di- and polyamine-caffeine analogues were synthesised and characterised by NMR, FT-IR, and MS spectroscopic methods. To access the stability of the investigated caffeine analogues, molecular dynamic simulations were performed in NAMD 2.9 assuming CHARMM36 force field. To evaluate the antioxidant capacity of new compounds, three different antioxidant assays were used, namely 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH

Topics: Amidines; Antioxidants; Biphenyl Compounds; Caffeine; Cell Survival; Chelating Agents; Cytotoxins; Erythrocytes; Hemolysis; Humans; Inhibitory Concentration 50; Iron; MCF-7 Cells; Organ Specificity; Oxidants; Oxidation-Reduction; Picrates; Polyamines; Structure-Activity Relationship

A new polysaccharide fraction (CCPP-1) was obtained from Craterellus cornucopioides. CCPP-1 had an average molecular weight of 9.2 × 10

Topics: Agaricales; Amidines; Animals; Antioxidants; Apoptosis; Benzothiazoles; Biphenyl Compounds; Carbon-13 Magnetic Resonance Spectroscopy; Catalase; Erythrocytes; Free Radical Scavengers; Fruiting Bodies, Fungal; Glutathione Peroxidase; Male; Malondialdehyde; Methylation; Mice; Molecular Weight; Monosaccharides; Picrates; Polysaccharides; Protective Agents; Proton Magnetic Resonance Spectroscopy; Reactive Oxygen Species; Spectroscopy, Fourier Transform Infrared; Sulfonic Acids

Dried citrus peel derived from Citrus reticulata, also called "chenpi", possesses a complex mixture of flavonoids and has a history of traditional use to treat a variety of digestive disorders. We compared three sources of conventional chenpi from California (USA), Guangxi, Zhejiang, and two sources of "nchenpi", which contain greater nobiletin content, from Sichuan and Xinhui (China). Xinhui orange peel extract (OPE) had highest content of polymethoxylated flavones, along with greatest capacity to scavenge 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-pcrylhydrazyl (DPPH), and 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) radicals and nitric oxide (NO). OPE also had higher NO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) inhibitory activity than an equivalent mixture of flavonoids (P<0.05). In conclusion, nobiletin is a good chemical marker for assessing the anti-inflammatory potential of OPE from different sources. Obtaining "nchenpi" from either Sichuan or Xinhui provided potentially superior health benefits compared to conventional chenpi sources.

Topics: Amidines; Animals; Anti-Inflammatory Agents; Antioxidants; Benzothiazoles; Biphenyl Compounds; California; Cell Survival; China; Chromatography, High Pressure Liquid; Citrus; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drugs, Chinese Herbal; Flavones; Flavonoids; Fruit; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Phenols; Picrates; Plant Extracts; RAW 264.7 Cells; Sulfonic Acids

The objective of this study was to evaluate the use of inulin (IN), a prebiotic carbohydrate without superficial activity, as an encapsulating matrix of lipophilic bioactive compounds. For achieving the encapsulation, IN was associated with biopolymers that present superficial activity: modified starch (HiCap), whey protein isolate (WPI) and gum acacia (GA). Encapsulation was performed through emulsification assisted by ultrasound followed by freeze-drying (FD) process to dry the emulsions. All blends retained geranylgeraniol. GA-IN blend yielded the highest geranylgeraniol retention (96±2wt.%) and entrapment efficiency (94±3wt.%), whilst WPI-IN blend yielded the highest encapsulation efficiency (88±2wt.%). After encapsulation, composition of geranylgeraniol in the annatto seed oil was maintained (23.0±0.5g/100g of oil). Such findings indicate that the method of encapsulation preserved the active compound. All blends were also effective for maintaining the antioxidant activity of the oil through ORAC and DPPH analyses.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Bixaceae; Chromans; Cichorium intybus; Diterpenes; Emulsions; Gum Arabic; Inulin; Oxygen Radical Absorbance Capacity; Particle Size; Picrates; Plant Oils; Prebiotics; Starch; Water; Whey Proteins; Zea mays

The in vitro and in vivo antioxidant potentials of a polysaccharide isolated from aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera gel by using ten digestive enzymes including five carbohydrases and five proteases. Among them, the highest yield was obtained with the Viscozyme extract and the same extract showed the best radical scavenging activity. An active polysaccharide was purified from the Viscozyme extract using ethanol-added separation and anion exchange chromatography. Purified aloe vera polysaccharide (APS) strongly scavenged radicals including DPPH, hydroxyl and alkyl radicals. In addition, APS showed a protective effect against AAPH-induced oxidative stress and cell death in Vero cells as well as in the in vivo zebrafish model. In this study, it is proved that both the in vitro and in vivo antioxidant potentials of APS could be further utilized in relevant industrial applications.

Topics: Aloe; Amidines; Animals; Antioxidants; Biphenyl Compounds; Cell Survival; Chlorocebus aethiops; Chromatography, Ion Exchange; Embryo, Nonmammalian; Glycoside Hydrolases; Hydroxyl Radical; Isoenzymes; Multienzyme Complexes; Oxidants; Peptide Hydrolases; Picrates; Plant Extracts; Plant Leaves; Polysaccharides; Vero Cells; Zebrafish

The anti-nociceptive and antioxidant activities of the Anadenantheracolubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 μg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 μg/mL) of lipid peroxidation caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly (p < 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly (p < 0.001) reduced by up to 79% at 400 mg/kg, while 56-60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100-400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms.

Topics: Amidines; Analgesics; Animals; Antioxidants; Biphenyl Compounds; Capsaicin; Colubrina; Fabaceae; Glutamic Acid; Lipid Peroxidation; Male; Mice; Pain; Pain Measurement; Phytotherapy; Picrates; Plant Bark; Plant Extracts; Plant Stems

Coumestan is a natural tetracycle with a C═C bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(•+)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by (•)OH, Cu(2+)/glutathione (GSH), and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit (•)OH-, Cu(2+)/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit (•)OH- and Cu(2+)/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant.

Topics: Amidines; Antioxidants; Benzofurans; Biphenyl Compounds; Coumarins; DNA; Glutathione; Hydroxyl Radical; Oxidation-Reduction; Picrates

The aim of this study was to investigate the antioxidant potential of ampelopsin (APS) by using various methods in vitro, as well as to determine effects of APS on LPS-induced oxidative stress in piglets. The results showed that APS exhibited excellent free radical scavenging by DPPH, ABTS, O2•-, H2O2 and ferric reducing antioxidant power. Ampelopsin also protected pig erythrocytes against AAPH-induced apoptosis and hemolysis, decreased total superoxide dismutase activity, and increased lipid peroxidation. Furthermore the results demonstrated that APS enhanced the total antioxidant capacity and decreased the malondialdehyde and protein carbonyl contents in LPS-treated piglets. The results of the present investigation suggest that APS possesses a strong antioxidant activity and alleviates LPS-induced oxidative stress, possibly due to its ability to prevent reactive oxygen species.

Topics: Amidines; Animals; Antioxidants; Apoptosis; Benzothiazoles; Biphenyl Compounds; Erythrocytes; Female; Flavonoids; Hemolysis; Hydrogen Peroxide; Inflammation; Injections, Intraperitoneal; Lipid Peroxidation; Lipopolysaccharides; Malondialdehyde; Oxidants; Oxidative Stress; Picrates; Protein Carbonylation; Sulfonic Acids; Superoxide Dismutase; Superoxides; Swine

Aim of this study was to elucidate lutein oxidation products mediated through peroxyl radical inducer 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH) and to study antioxidant and cytotoxic effects of oxidized lutein using liposome and HeLa cells. Lutein (20 μmol) with AAPH (5 mM) in liposome's was incubated at 37 °C in dark for 3 h, oxidized lutein products were characterized by LC-MS (APCI(+)) and studied for their free radical scavenging activity and cytotoxic effects in terms of cell viability, cellular glutathione, and malondialdehyde levels. AAPH mediated lutein fragmented ions were identified as 551 (M(+)+H(+)-H(2)O), 391 (M(+)+H(+)+O(2)-C(22)H(32)O) and 276 (M(+)+H(+)+O(2)-C(12)H(20)O) and its isomers as 13-Z lutein, 13-Z zeaxanthin, 13'-Z zeaxanthin and all-E zeaxanthin. Free radical scavenging activity of oxidized lutein was higher by 32.7% (IC(50), 2.64 μg) than lutein (IC(50), 5.28 μg). Oxidized lutein lowered the lipid peroxidation (21%), HeLa cells viability (22%) and glutathione levels (32%) than lutein. To conclude, the oxidized lutein may be highly reactive, since oxidation by AAPH results in peroxyl radical ions, which can react with conjugated polyene chain of lutein that could lead to higher antioxidant and cytotoxic effects on HeLa cells.

Topics: Amidines; Antineoplastic Agents; Biphenyl Compounds; Drug Interactions; Free Radical Scavengers; HeLa Cells; Humans; Lutein; Oxidation-Reduction; Peroxides; Picrates

The subject of this study was the hexahydropyridoindole compound SMe1EC2 with reported antioxidant and neuroprotective effects and low toxicity. In this study, the antioxidant action of SMe1EC2 was investigated in a greater detail in the system of isolated rat erythrocytes.. First, the compound was subjected to the DPPH test. Second, the overall antioxidant action of the compound was studied in the cellular system of isolated rat erythrocytes oxidatively stressed by free radicals derived from either the hydrophilic azoinitiator AAPH or the lipophilic t-BuOOH, and compared with reference antioxidants.. The DPPH test revealed significant antiradical activity of SMe1EC2 comparable with that of the standard trolox. In the cellular system, SMe1EC2 protected red blood cells against free radical-initiated hemolysis. The overall antioxidant efficacy of SMe1EC2 relative to the reference antioxidant stobadine was strongly affected by the lipophilicity of the initiating free radical species.. The results proved high antiradical efficacy of SMe1EC2. In the system of t-BuOOH/isolated erythrocytes, a model cellular system of endogenously generated peroxyl radicals, SMe1EC2 significantly exceeded the parent stobadine in its antioxidant action. Considering the reported results of preclinical studies of SMe1EC2 showing its profound neuroprotective effects and low toxicity, the compound represents an example of a potential pharmacologically practicable antioxidant drug.

Topics: Amidines; Animals; Antioxidants; Biphenyl Compounds; Carbolines; Chromans; Erythrocytes; Hemolysis; Indoles; Male; Peroxides; Picrates; Pyridines; Rats; Rats, Wistar

Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit (·)OH-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu(2+)/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+.)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant.

Topics: Amidines; Benzothiazoles; Biphenyl Compounds; Chemistry Techniques, Synthetic; DNA; Free Radical Scavengers; Free Radicals; Glutathione; Hydroxyl Radical; Kinetics; Oxadiazoles; Oxidation-Reduction; Picrates; Sulfonic Acids

A series of 4-methylcoumarin derivatives containing 4,5-dihydropyrazole moiety were synthesized and their antioxidant activities were evaluated in AAPH (2,2'-azobis(2-amidinopropane hydrochloride))-induced oxidation of DNA, and in trapping DPPH (2,2'-diphenyl-1-picrylhydrazyl) and ABTS(+•) (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical), respectively. Among coumarin derivatives, 3a-d and 4a-c exhibited the termination of radical propagation-chains in AAPH-induced oxidation of DNA. The ortho dihydroxyphenyl substitution at 5 position and 1-unsubstitution of the 4,5-dihydroxylpyrazole was found enhancing the antioxidant activities of these coumarin derivatives.

Topics: Amidines; Benzothiazoles; Biphenyl Compounds; Chemistry Techniques, Synthetic; Coumarins; DNA; Free Radical Scavengers; Oxidation-Reduction; Picrates; Pyrazoles; Sulfonic Acids

Some of the major components of Danshen (Salvia miltiorrhiza), a widely used Chinese herbal medicine rich in phenolic acids, are thermosensitive and may degrade to other phenolic acids during extractions with heating. The chemical profiles of Danshen water-extract may vary with different heat water extraction at different temperatures, affecting the composition and bioactivity of the extracts. In this study, six water-extracts of Danshen obtained from heat reflux water extraction and microwave-assisted extraction with water (MAE-W) at different temperatures were tested for their composition and pharmacological effects. Among these extracts, the third-round MAE-W (100°C) extract had the highest phenolic acids and tanshinones contents, with the strongest antioxidant activity in 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay and ferric reducing/antioxidant potential (FRAP) assay. This extract also showed the strongest inhibitory effects on 2,2'-azobis-2-amidinopropane (AAPH)-induced hemolysis in human red blood cells, hydrogen peroxide-induced apoptosis in rat heart H9c2 cells and the highest relaxation effects on rat basilar artery. The antioxidant effects of Danshen water-extracts linearly correlated to their relaxation effects (r=0.895-0.977). Through multiple linear regression analysis, danshensu was found to be the most significant marker in the antioxidant and vasodilation effects of Danshen water-extract, while tanshinone IIA as the marker on hydrogen peroxide-induced apoptosis in rat heart H9c2 cells. Danshensu is, therefore, a useful marker for the quality control of Danshen water-extracts in antioxidant and vasodilation, while tanshinone IIA for anti-apoptotic potential of different extracts.

Topics: Abietanes; Amidines; Animals; Antioxidants; Apoptosis; Basilar Artery; Biphenyl Compounds; Cell Line; Drugs, Chinese Herbal; Erythrocytes; Ferric Compounds; Heart; Hemolysis; Hot Temperature; Humans; Hydrogen Peroxide; Lactates; Phenols; Picrates; Rats; Salvia miltiorrhiza; Vasodilation; Vasodilator Agents

Oxidative stress is involved in the pathogenesis of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Astrocytes, the most abundant glial cells in the brain, protect neurons from reactive oxygen species (ROS) and provide them with trophic support, such as glial-derived neurotrophic factor (GDNF). Thus, any damage to astrocytes will affect neuronal survival. In the present study, an infusion prepared from the desert plant Pulicaria incisa (Pi) was tested for its protective and antioxidant effects on astrocytes subjected to oxidative stress. The Pi infusion attenuated the intracellular accumulation of ROS following treatment with hydrogen peroxide and zinc and prevented the H(2)O(2)-induced death of astrocytes. The Pi infusion also exhibited an antioxidant effect in vitro and induced GDNF transcription in astrocytes. It is proposed that this Pi infusion be further evaluated for use as a functional beverage for the prevention and/or treatment of brain injuries and neurodegenerative diseases in which oxidative stress plays a role.

Topics: Amidines; Animals; Antioxidants; Astrocytes; Biphenyl Compounds; Cell Death; Chlorides; Cytoprotection; Free Radical Scavengers; Gene Expression Regulation; Glial Cell Line-Derived Neurotrophic Factor; Hydrogen Peroxide; Oxidation-Reduction; Peroxides; Picrates; Plant Extracts; Pulicaria; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Zinc Compounds

Cinnamoylphenethylamine (CNPA) derivatives including feruloylphenethylamine (FRPA), caffeoylphenethylamine (CFPA), cinnamoyltyramine (CNTA), feruloyltyramine (FRTA) and caffeoyltyramine (CFTA) were synthesized in order to investigate the influence of the number and position of hydroxyl group on Cu(2+)/glutathione (GSH) and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. The radical-scavenging properties of these CNPA derivatives were also evaluated by trapping 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonate) cationic radical (ABTS(+•)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and galvinoxyl radical. In addition, these CNPA derivatives were tested by linoleic acid (LH)-β-carotene-bleaching experiment. The chemical kinetic was employed to treat the results from AAPH-induced oxidation of DNA and gave the order of antioxidant ability as CFTA > CFPA > FRTA > FRPA. CFTA and CFPA also possessed high abilities to inhibit Cu²(+)/GSH-mediated degradation of DNA, whereas FRPA and FRTA can protect LH against the auto-oxidation efficiently. Finally, CFPA and FRPA exhibited high activity in trapping ABTS(+•), DPPH and galvinoxyl radicals. Therefore, the cinnamoyl group bearing ortho-dihydroxyl or hydroxyl with ortho-methoxyl benefited for CNPA derivatives to protect DNA, while hydroxyl in tyramine cannot enhance the radical-scavenging abilities of CNPA derivatives.

Topics: Amidines; Antioxidants; Benzhydryl Compounds; Benzothiazoles; beta Carotene; Biphenyl Compounds; Cinnamates; Copper; DNA; Free Radical Scavengers; Glutathione; Hydroxides; Linoleic Acid; Oxidation-Reduction; Phenethylamines; Picrates; Solutions; Structure-Activity Relationship; Sulfonic Acids

Several studies suggest that regular consumption of nuts, mostly walnuts, may have beneficial effects against oxidative stress mediated diseases such as cardiovascular disease and cancer. Walnuts contain several phenolic compounds which are thought to contribute to their biological properties. The present study reports the total phenolic contents and antioxidant properties of methanolic and petroleum ether extracts obtained from walnut (Juglans regia L.) seed, green husk and leaf. The total phenolic contents were determined by the Folin-Ciocalteu method and the antioxidant activities assessed by the ability to quench the stable free radical 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and to inhibit the 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of human erythrocytes. Methanolic seed extract presented the highest total phenolic content (116 mg GAE/g of extract) and DPPH scavenging activity (EC(50) of 0.143 mg/mL), followed by leaf and green husk. In petroleum ether extracts, antioxidant action was much lower or absent. Under the oxidative action of AAPH, all methanolic extracts significantly protected the erythrocyte membrane from hemolysis in a time- and concentration-dependent manner, although leaf extract inhibitory efficiency was much stronger (IC(50) of 0.060 mg/mL) than that observed for green husks and seeds (IC(50) of 0.127 and 0.121 mg/mL, respectively). Walnut methanolic extracts were also assayed for their antiproliferative effectiveness using human renal cancer cell lines A-498 and 769-P and the colon cancer cell line Caco-2. All extracts showed concentration-dependent growth inhibition toward human kidney and colon cancer cells. Concerning A-498 renal cancer cells, all extracts exhibited similar growth inhibition activity (IC(50) values between 0.226 and 0.291 mg/mL), while for both 769-P renal and Caco-2 colon cancer cells, walnut leaf extract showed a higher antiproliferative efficiency (IC(50) values of 0.352 and 0.229 mg/mL, respectively) than green husk or seed extracts. The results obtained herein strongly indicate that walnut tree constitute an excellent source of effective natural antioxidants and chemopreventive agents.

Topics: Amidines; Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Caco-2 Cells; Cell Proliferation; Erythrocytes; Free Radical Scavengers; Free Radicals; Hemolysis; Humans; In Vitro Techniques; Indicators and Reagents; Juglans; Nuts; Phenols; Picrates; Plant Extracts; Plant Leaves

Dietary polyphenols are beneficial to human health by exerting various biological effects. Ferulic and caffeic acids are hydroxycinnamic acid derivatives widely distributed in plant-derived food products. Studies indicate that some dietary compounds may have concentration-dependent antioxidant or prooxidant activities. The present study concerns such activities of ferulic and caffeic acids. They have concentration-dependent antioxidant effects in terms of inhibition of lipid peroxidation and reactive oxygen species-scavenging after 2,2'-azobis-amidinopropane dihydrochloride-induced damage in mouse liver microsomes and splenic lymphocytes respectively. They also show differential scavenging of nitric oxide, superoxide and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid radical (ABTS*(+)). In DPPH (1,1-diphenyl picrylhydrazyl) assay above 20 μM the absorbance start increasing due to the formation of an unknown adduct which has a shoulder at 517 nm. However, in Fenton reaction, above 5 μM, they behave as prooxidants and the possible mechanisms responsible for their prooxidant property may be related to their ferric reducing ability. These findings may have significant health implications where these natural compounds are being used/consumed.

Topics: Amidines; Animals; Antioxidants; Benzothiazoles; Biphenyl Compounds; Caffeic Acids; Coumaric Acids; Ferric Compounds; Free Radical Scavengers; Hydroxyl Radical; In Vitro Techniques; Lipid Peroxidation; Male; Mice; Microsomes, Liver; Nitric Oxide; Oxidants; Picrates; Reducing Agents; Sulfonic Acids; Superoxides

The aim of this study was to determine the phenolic content and evaluate the antioxidant activity of quince (Cydonia oblonga) fruit. For this purpose, fruits were separated into pulps, peels and seeds and methanolic extracts were prepared. The phenolic profiles were determined by HPLC/UV and antioxidant properties were studied for their ability to quench the stable free radical 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and to inhibit the 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of human erythrocytes. The main phenolic compounds were 5-O-caffeoylquinic acid for pulp and peel (57% and 29%, respectively) and stellarin-2 for seed (18%). Total phenolics content was 2.5, 6.3 and 0.4g/kg of methanolic extract for pulp, peel and seed, respectively. Pulp and peel extracts showed similar DPPH free radical scavenging activities (EC(50) of 0.6 and 0.8 mg/ml, respectively), while seed extract presented much lower antioxidant potential (EC(50) of 12.2mg/ml). Under the oxidative action of AAPH, pulp and peel extracts showed significant protection of the erythrocyte membrane from hemolysis, in a time- and concentration-dependent manner. Seed extracts by themselves induced extensive hemolysis. These results indicate higher antioxidant activity for certain parts of quince fruit, namely pulp and peel, that may therefore represent accessible sources of natural antioxidants with potential application in nutritional/pharmaceutical fields, as preventive or therapeutic agents in diseases in which free radicals are implicated.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Chromatography, High Pressure Liquid; Erythrocyte Membrane; Erythrocytes; Fatty Acids, Nonesterified; Free Radical Scavengers; Fruit; Hemolysis; Humans; In Vitro Techniques; Lipid Peroxidation; Membrane Lipids; Oxidants; Oxidation-Reduction; Phenols; Picrates; Plant Extracts; Rosaceae; Spectrophotometry, Ultraviolet

A polyacrylic acid (PAA)-protected platinum nanoparticle species (PAA-Pt) was prepared by alcohol reduction of hexachloroplatinate. The PAA-Pt nanoparticles were well dispersed and homogeneous in size with an average diameter of 2.0 +/- 0.4 nm (n = 200). We used electron spin resonance to quantify the residual peroxyl radical ([Formula: see text]) generated from 2,2-azobis (2-aminopropane) dihydrochloride (AAPH) by thermal decomposition in the presence of O(2) and a spectrophotometric method to quantify the residual 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. PAA-Pt scavenged these two radicals in a dose-dependent manner. Platinum was the functional component. PAA-Pt reduced the rate of oxygen consumption required for linoleic acid peroxidation initiated by [Formula: see text] generated from AAPH, indicating inhibition of the propagation of linolate peroxidation. A thiobarbituric acid test also revealed dose-dependent inhibition of the linolate peroxidation by PAA-Pt. Fifty micromolar platinum, as PAA-Pt, completely quenched 250 microM DPPH radical for 5 min. Even when twice diluted in half, the PAA-Pt still quenched 100% of the 250 microM DPPH radical. The scavenging activity of PAA-Pt is durable. These observations suggest that PAA-Pt is an efficient scavenger of free radicals.

Topics: Amidines; Biphenyl Compounds; Free Radical Scavengers; Linoleic Acid; Lipid Peroxidation; Metal Nanoparticles; Peroxides; Picrates; Platinum

Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were highly active as free radical scavengers against ABTS, DPPH (hydrogen donation and electron transfer), and HNTTM (electron transfer). They were also able to reduce the newly introduced TNPTM radical, meaning that they included some highly reactive components. Witch hazel phenolics protected red blood cells from free radical-induced hemolysis and were mildly cytotoxic to 3T3 fibroblasts and HaCat keratinocytes. They also inhibited the proliferation of tumoral SK-Mel 28 melanoma cells at lower concentrations than grape and pine procyanidins. The high content in pyrogallol moieties may be behind the effect of witch hazel phenolics on skin cells. Because the most cytotoxic and antiproliferative mixtures were also the most efficient as electron transfer agents, we hypothesize that the final putative antioxidant effect of polyphenols may be in part attributed to the stimulation of defense systems by mild prooxidant challenges provided by reactive oxygen species generated through redox cycling.

Topics: 3T3 Cells; Amidines; Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromatography, High Pressure Liquid; Cysteamine; Electron Transport; Erythrocytes; Fibroblasts; Gallic Acid; Hamamelis; Humans; Keratinocytes; Magnetic Resonance Spectroscopy; Melanoma; Mice; Picrates; Plant Bark; Skin; Solvents; Sulfhydryl Compounds; Tannins

The antioxidant properties of different almond cultivars (cv.), either regional (Casanova, Duro Italiano, Molar, Orelha de Mula and Pegarinhos cv.) or commercial (Ferraduel, Ferranhês, Ferrastar and Guara cv.) were evaluated through several chemical and biochemical assays: DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, reducing power, inhibition of beta-carotene bleaching, inhibition of oxidative hemolysis in erythrocytes, induced by 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), and inhibition of thiobarbituric acid reactive substances (TBARS) formation in brain cells, all used as models for the lipid peroxidation damage in biomembranes. The EC50 values were calculated for all the methods in order to evaluate the antioxidant efficiency of each almond cultivar. Bioactive compounds such as phenols and flavonoids were also obtained and correlated to antioxidant activity. The results obtained were quite heterogeneous, revealing significant differences among the cultivars assayed. Duro Italiano cv. revealed better antioxidant properties, presenting lower EC50 values in all assays, and the highest antioxidants contents. The protective effect of this cultivar on erythrocyte biomembrane hemolysis was maintained during 4h.

Topics: Amidines; Animals; Antioxidants; beta Carotene; Biphenyl Compounds; Brain; Brain Chemistry; Erythrocytes; Free Radical Scavengers; Hemolysis; Male; Oxidation-Reduction; Oxidative Stress; Picrates; Portugal; Prunus; Sheep; Swine; Thiobarbituric Acid Reactive Substances

The antioxidant activities of curcumin, its natural demethoxy derivatives (demethoxycurcumin, Dmc and bisdemethoxycurcumin, Bdmc) and metabolite hydrogenated derivatives (tetrahydrocurcumin, THC; hexahydrocurcumin, HHC; octahydrocurcumin; OHC) were comparatively studied using 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) induced linoleic oxidation and AAPH induced red blood cell hemolysis assays. Hydrogenated derivatives of curcumin exhibited stronger DPPH scavenging activity compared to curcumin and a reference antioxidant, trolox. The scavenging activity significantly decreased in the order THC>HHC=OHC>trolox>curcumin>Dmc>>>Bdmc. Stronger antioxidant activities toward lipid peroxidation and red blood cell hemolysis were also demonstrated in the hydrogenated derivatives. By the model of AAPH induced linoleic oxidation, the stoichiometric number of peroxyl radical that can be trapped per molecule (n) of hydrogenated derivatives were 3.4, 3.8 and 3.1 for THC, HHC and OHC, respectively. The number (n) of curcumin and Dmc were 2.7 and 2.0, respectively, which are comparable to trolox, while it was 1.4 for Bdmc. The inhibition of AAPH induced red blood cell hemolysis significantly decreased in the order OHC>THC=HHC>trolox>curcumin=Dmc. Results in all models demonstrated the lower antioxidant activity of the demethoxy derivatives, suggesting the ortho-methoxyphenolic groups of curcumin are involved in antioxidant activities. On the other hand, hydrogenation at conjugated double bonds of the central seven carbon chain and beta diketone of curcumin to THC, HHC and OHC remarkably enhance antioxidant activity.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Chromans; Curcumin; Diarylheptanoids; Erythrocyte Membrane; Free Radical Scavengers; Free Radicals; Hemolysis; Humans; Hydrogenation; In Vitro Techniques; Linoleic Acid; Lipid Peroxidation; Molecular Structure; Oxidants; Picrates; Structure-Activity Relationship; Time Factors

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.

Topics: Amidines; Animals; Antioxidants; Benzoquinones; Biphenyl Compounds; Drug Interactions; Free Radical Scavengers; Hydrazines; Hydroxyl Radical; Lipid Peroxidation; Liver; Male; Mitochondria, Liver; Oxidation-Reduction; Picrates; Potentiometry; Pulse Radiolysis; Rats; Reactive Oxygen Species; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The antioxidant profile of extracts from solid olive residue (SOR) of c.v. Coratina, a cultivar widely diffused in the south of Italy, using both cell-free and cell-based experimental models, was investigated. A total hydroalcoholic extract (polyphenols content 19.7%) and a purified extract (Oleaselecttrade mark) (polyphenols content 35.1%) were tested for their ability to quench the stable free radical DPPH, the peroxyl radicals (ORAC assay), by monitoring the loss in fluorescence of R-phycoerythrin induced by the peroxyl radical generator AAPH and their ability to inhibit the cumene hydroperoxide-induced lysis of rat red blood cells (RBC). The total hydroalcoholic extract showed IC(50) 26.96+/-1.53 microg/ml in the DPPH assay, that 10 microg/ml were equivalent to 2.11+/-0.12 microg/ml Trolox (ORAC assay) and IC(50) 1.7+/-0.20 microg/ml in the RBC hemolysis. The Oleaselect extract was 4 to 5 folds more active than the hydroalcoholic extract in all the experimental models, with IC(50) values of 7.36+/-0.38 microg/ml in the DPPH test and of 0.38+/-0.03 microg/ml in RBC; the antioxidant activity in the ORAC assay was slightly greater than that of Trolox (10 microg/ml equivalent to 11.45+/-0.40 microg/ml). The scavenging effect of the extract in the ORAC assay was compared to that of verbascoside (the main polyphenol component) and of caffeic acid (the basic constituent of verbascoside): the results indicate that caffeic acid (10 microg/ml equivalent to 35.70+/-2.95 microg/ml Trolox) is more potent than verbascoside (10 microg/ml equivalent to 15.42+/-1.21 microg/ml Trolox) in entrapping peroxyl radicals. Finally the antioxidant activity of the Oleaselect extract was confirmed in human umbilical endothelial cells (EC) exposed to the site-specific peroxyl radical inducer AAPH, where a massive lipid peroxidation process (marker the fluorescence probe BODIPY) takes place, paralleled by a marked loss of cell viability (calcein assay). The purified extract (1-20 microg/ml) pre-incubated with EC for 1 h dose-dependently inhibited both the lipid-peroxidation damage and cell death. Taking into account the total polyphenol content, these results clearly indicate a greater antioxidant activity for the purified extract, due to a cooperative antioxidant interaction among its polyphenol constituents.

Topics: Amidines; Animals; Antioxidants; Biphenyl Compounds; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; Flavonoids; Free Radicals; Hemolysis; Humans; Hydrazines; Male; Olea; Phenols; Picrates; Plant Extracts; Polyphenols; Rats; Rats, Wistar

The oxidized low-density lipoprotein (ox-LDL) plays a critical role at the early stages of atherosclerosis. Thus, the prevention of LDL-oxidation by antioxidants may arrest the progression of atherosclerosis. Two quinoline alkaloids, 3,8-dihydroxyquinoline (1) and 2,8-dihydroxy-3,4-dimethoxyquinoline (3), and 2,4-di-tert-butylphenol (2) were isolated from the dried body of Scolopendra subspinipes. Compounds 1-3 exhibited antioxidant activities on copper-mediated (1: IC50=2.6 microM, 2: IC50=8.2 microM, 3: IC50=63.0 microM), AAPH-mediated oxidation (1: IC50=3.9 microM, 2: IC50=9.9 microM, 3: IC50=71.8 microM), and SIN-1-mediated oxidation (1: 70%, 2: 52%, 3: 29% at 5.0 microM) in the TBARS assay. The antioxidant activities of compounds 1-3 were tested with respect to other parameters, such as the lag time of conjugated diene fromation, relative electrophoretic mobility (REM) of ox-LDL, and apoB-100 fragmentation on copper-mediated LDL-oxidation. In addition, compounds 1-3 showed 1,1-diphenyl-2-picrylhydrasyl (DPPH) radical scavenging activity and compound 1 also exhibited metal chelating activity.

Topics: Alkaloids; Amidines; Animals; Antioxidants; Apolipoprotein B-100; Apolipoproteins B; Arthropods; Biphenyl Compounds; Chelating Agents; Copper; Electrophoretic Mobility Shift Assay; Free Radical Scavengers; Lipoproteins, LDL; Molsidomine; Oxidation-Reduction; Oxyquinoline; Picrates; Quinolines; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Thiobarbituric Acid Reactive Substances

The enzymatic hydrolysates from pollen Cistus ladaniferus were digested and prepared using three kinds of enzymes (pepsin, trypsin, and papain) and the antioxidative properties were investigated. The yields, total phenolic contents, and protein contents of these hydrolysates were as follows: yields (about 21-45%), total phenolics (10.39-14.33 microg/mg sample powder), and proteins (129.62-137.35 microg/mg sample powder), respectively. The hydrolysates possessed strongly antioxidative and scavenging abilities against reactive oxygen species. The present studies revealed that hydrolysates from honeybee-collected pollen are of benefit not only to the materials of health food diets, but also to patients with various diseases such as cancer, cardiovascular diseases, and diabetes.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Cistus; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Hydroxyl Radical; Indicators and Reagents; Linoleic Acid; Oxidants; Oxygen; Papain; Pepsin A; Phenol; Picrates; Pollen; Protein Hydrolysates; Reactive Oxygen Species; Superoxides; Time Factors; Trypsin

The radical scavenging effect and protective potential from oxidative damage by radical generator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), in renal epithelial LLC-PK1 cell of broccoli (Brassica oleracea) were investigated and identified the active components under the bioassay-linked fractionation method. The MeOH extract, and fractions of CH2Cl2, BuOH and H2O from broccoli showed the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect in a dose-dependent manner. In addition, they exerted the protective effect against LLC-PK1 cellular damage induced by AAPH dose-dependently. In particular, the BuOH fraction was evaluated as the most active fraction, indicating that the BuOH fraction contains the active components with antioxidative capacity. Employing a bioassay-linked fractionation method, the active principles were isolated and characterized as 1,2-disinapoylgentiobiose and 1-sinapoyl-2-feruloylgentiobiose from the BuOH fraction. These two compounds from broccoli displayed potent antioxidant effects against the DPPH radical, showing the IC50 values of 5.18 and 7.52 microg/mL, respectively. Moreover, the compounds significantly and dose-dependently recovered cell viability lowered by AAPH treatment, suggesting the protective roles from cellular oxidative damage. The present study suggests that broccoli has excellent antioxidative potential and the hydroxycinamic acid esters from broccoli, 1,2-disinapoylgentiobiose and 1-sinapoyl-2-feruloylgentiobiose, are considered as the active components with antioxidative effect.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Brassica; Cell Line; Coumaric Acids; Disaccharides; Epithelium; Free Radical Scavengers; Kidney; Methanol; Oxidants; Oxidative Stress; Picrates; Plant Extracts

The methylene chloride extract of the root of Angelicae dahuricae showed high protective activity against 2,2'-azobis (2-aminodinopropane) dihydrochloride (AAPH)-induced cellular damage. From this extract, 11 furanocoumarins were isolated, namely oxypeucedanin hydrate, 9-hydroxy-4-methoxypsoralen, byakangelicin, pabulenol, alloisoimperatorin, neobyakangelicol, byakangelicol, oxypeucedanin, imperatorin, phellotorin and isoimperatorin, respectively. Among these 11 furanocoumarins, 9-hydroxy-4-methoxypsoralen and alloisoimperatorin displayed potent antioxidant effects against the DPPH radical and against renal epithelial cell injury by using AAPH to generate peroxyl radicals in vitro.

Topics: Amidines; Animals; Antioxidants; Apiaceae; Biphenyl Compounds; Cell Survival; Furocoumarins; LLC-PK1 Cells; Phytotherapy; Picrates; Plant Extracts; Plant Roots; Swine

Twenty flavonoid compounds of five different subclasses were selected, and the relationship of their structure to the inhibition of low-density lipoprotein (LDL) oxidation in vitro was investigated. The most effective inhibitors, by either copper ion or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) induction, were flavonols and/or flavonoids with two adjacent hydroxyl groups at ring B. In the presence of the later catechol group, the contribution of the double bond and the carbonyl group at ring C was negligible. Isoflavonoids were more effective inhibitors than other flavonoid subclasses with similar structure. Substituting ring B with hydroxyl group(s) at 2' position resulted in a significantly higher inhibitory effect than by substituting ring A or ring B at other positions. The type of LDL inducer had no effect in flavonoids with catechol structure. Calculated heat of formation data (deltadeltaH(f)) revealed that the donation of a hydrogen atom from position 3 was the most likely result, followed by that of a hydroxyl from ring B. Position 3 was favored only in the presence of conjugated double bonds between ring A to ring B. This study makes it possible to assign the contribution of different functional groups among the flavonoid subclasses to in vitro inhibition of LDL oxidation.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Cholesterol, LDL; Copper; Flavonoids; Free Radicals; Humans; Molecular Structure; Oxidation-Reduction; Picrates; Structure-Activity Relationship; Thermodynamics

4-(4-Hydroxyphenyl)-5-(4-hydroxyphenylmethyl)-2-hydroxyfurane-2-one 1 was prepared by an acidic dimerisation of 4-hydroxyphenylpyruvic acid and some of its antioxidant and spectroscopic properties have been measured and compared to that of ascorbic acid. 1 is as good an antioxidant as ascorbic acid in the DPPH (2,2-diphenyl-1-picryl hydrazyl radical) test and the inhibition of hydroxyl radical and a powerful inhibitor of the Cu(2+) or AAPH (2,2'-azobis-(2-amidinopropane) dihydrochloride) induced oxidation of human LDL. 1 gives a stable radical characterised by its ESR spectrum similarly to ascorbic acid but in lower concentration and with a different reactivity towards nitroxides. Theoretical calculations allow us to propose the structure for the radical formed from 1, to explain its lower stability than ascorbyl radical and to evaluate the lipophilicity of 1.

Topics: Amidines; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Chemical Phenomena; Chemistry, Physical; Cholesterol, LDL; Copper; Electromagnetic Fields; Electron Spin Resonance Spectroscopy; Furans; Humans; Hydroxyl Radical; Indicators and Reagents; Lipids; Models, Molecular; Molecular Conformation; Picrates; Spectrophotometry, Ultraviolet

We studied the antioxidative action to evaluate the effect of citrus essential oil components on human LDL in vitro. Among the authentic volatile compounds tested, gamma-terpinene showed the strongest antioxidative effect, and inhibited both the Cu(2+)-induced and AAPH-induced oxidation of LDL. gamma-Terpinene added after 30 min (mid-lag phase) and 60 min (propagation phase) of incubation of LDL with Cu(2+) inhibited LDL oxidation.

Topics: Amidines; Antioxidants; Biphenyl Compounds; Citrus; Copper; Cyclohexane Monoterpenes; Humans; Lipoproteins, LDL; Monoterpenes; Oils, Volatile; Picrates; Terpenes; Thiobarbituric Acid Reactive Substances

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.

Topics: Amidines; Biphenyl Compounds; DNA; DNA Damage; Dose-Response Relationship, Drug; Free Radical Scavengers; Free Radicals; Nanotechnology; Nitric Oxide; Oxidative Stress; Picrates; Selenium; Serum Albumin, Bovine; Singlet Oxygen; Superoxides

The antioxidant and prooxidant activities of flavonoids belonging to several classes were studied to establish their structure-activity relationships against different oxidants. Special attention was paid to the flavonoids quercetin (flavone), taxifolin (flavanone) and catechin (flavanol), which possess different basic structures but the same hydroxylation pattern (3,5,7,3'4'-OH). It was found that these three flavonoids exhibited comparable antioxidant activities against different oxidants leading to the conclusion that the presence of ortho-catechol group (3',4'-OH) in the B-ring is determinant for a high antioxidant capacity. The flavone kaempferol (3,5,7,4'-OH), however, in spite of bearing no catechol group, also presents a high antioxidant activity against some oxidants. This fact can be attributed to the presence of both 2,3-double bond and the 3-hydroxyl group, meaning that the basic structure of flavonoids becomes important when the antioxidant activity of B-ring is small.

Topics: Amidines; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Catechin; Edetic Acid; Flavonoids; Flavonols; Free Radicals; Iron; Kaempferols; Liposomes; Metmyoglobin; Picrates; Quercetin; Structure-Activity Relationship

The pro-oxidant activity of potent oxidants and foods was determined using the kinetic analysis of crocin bleaching. In its reduced form, crocin has an absorption band at 443 nm, which disappears upon oxidation by a generic radical species. Hydroxyl radicals generated by hydrogen peroxide, peroxyl radicals from ABAP, and the stable free radical DPPH(*) were allowed to react with crocin in an aqueous solution at 40 degrees C. Pro-oxidant activity was taken as the ratio between the decrease in crocin absorbance at 5 min and the relevant oxidant concentration. The test proposed was used to evaluate the pro-oxidant activity of widely consumed foods such as pasteurized skim milk and bread. They both exerted significant pro-oxidant activities, which were attributed to the early nonenzymatic browning products formed upon heat treatment.

Topics: Amidines; Animals; Bepridil; Biphenyl Compounds; Bread; Carotenoids; Chemical Phenomena; Chemistry, Physical; Food; Hydrogen Peroxide; Hydroxyl Radical; Kinetics; Milk; Oxidants; Oxidation-Reduction; Peroxides; Picrates; Solutions; Water

Three tests of increasing complexity were used to assess the antioxidant activity of five synthetic gallic esters of sucrose bearing 3, 6, 7, or 8 galloyl units. In addition, two of these compounds had 1 or 2 hydrocarbon (C10-C12) acyl chains. Reaction with the DPPH radical led to the evaluation of the number of radicals trapped per galloyl unit n (3-4), as well as the apparent second-order rate constant for H atom donation k (1200-1500/M/s). These results indicated similar contribution and reactivity of all the galloyl units. Inhibition of the AAPH-initiated peroxidation of linoleic acid in a micellar medium confirmed the additive contribution of the galloyl units, whereas the presence of the hydrocarbon acyl chains had no influence. These results suggest an inhibition of initiation at high antioxidant levels and an underlying prooxidant effect of the galloyl radicals at low concentrations. Finally, LDL peroxidation was inhibited in proportion to the number of galloyl units, in agreement with the preceding tests.

Topics: Amidines; Biphenyl Compounds; Esters; Free Radical Scavengers; Free Radicals; Gallic Acid; Hydrolyzable Tannins; Linoleic Acid; Lipid Peroxidation; Lipoproteins, LDL; Oxidants; Picrates; Sucrose; Tannins

Degenerative diseases such as cancer are induced by oxidative genetic damage. Antioxidants can scavenge reactive oxygen species, but to prevent disease, they must do so quickly, before the DNA bases are damaged. In the present study, a novel method was established for evaluating the potency of antioxidants employing 2'-deoxyguanosine as a target and 2,2'-azobis(2-amidino-propane) dihydrochloride as a reactive oxygen generator. The reaction formed one product linearly with time. This product was a novel 8-hydroperoxy-2'-deoxyguanosine (8-OOHdG). Using this system, 81 antioxidants occurring in our diet were assayed for activity to suppress the formation of 8-OOHdG by high-performance liquid chromatography (HPLC). The system was useful for the evaluation of antioxidative potency, compared to another method utilizing 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further, it was enabled to examine the synergism of antioxidants. The formation of 8-OOHdG started only after the antioxidants had been consumed. Ascorbic acid, quercetin, and epigallocatechin gallate together delayed the formation by the sum total of the delay times of each factor alone. The proposed method is simple and easy, and can evaluate which dietary antioxidants inhibit reactive oxygen species more quickly than the DNA bases are damaged.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Amidines; Antioxidants; Biphenyl Compounds; Deoxyguanosine; Drug Synergism; Free Radicals; Indicators and Reagents; Oxidants; Picrates; Reactive Oxygen Species

Four spectrophotometric methods of determination of antioxidant capacity: a method based on the scavenging of the l,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, the "ferric-reducing ability of plasma" (FRAP), a method based on reduction of the 2.2'-azinobis (3-ethylbenzthiazolinesulfonate) free radical (ABTS.+) and a kinetic method based on the oxidation of dihydro-2,7-dichlorofluorescein by 2,2'-azobis(2-amidopropane) (ABAP) were compared with respect to standard antioxidants (ascorbate, glutathione, Trolox and urate) and human blood plasma. Various reactivities of standard antioxidants in different tests were found. glutathione showing a low reactivity in the FRAP assay. Kinetic measurements show that the reduction of indicators, especially by blood plasma, may not be complete at recommended times of the assays and the time of measurement is an important parameter when comparing the results.

Topics: Adult; Amidines; Antioxidants; Ascorbic Acid; Benzothiazoles; Biphenyl Compounds; Chemistry, Clinical; Female; Glutathione; Humans; Kinetics; Male; Middle Aged; Oxidative Stress; Picrates; Plasma; Spectrophotometry; Sulfonic Acids; Uric Acid

The aim of this paper was to clarify whether the interaction of the lazaroid U-74389G with phospholipid membranes might be relevant as to its antioxidant activity. Thus we evaluated the "in vitro" antioxidant activity of U-74389G in two experimental models: 1) bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical; 2) peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidino-propane) hydrochloride, on mixed dipalmitoyl-phosphatidylcholine/linoleic acid unilamellar vesicles. Moreover, given that biophysical techniques may help in explaining the role of a drug in its interaction with the microenvironment of the model lipid membranes, we used a classical approach to investigate the U-74389G/model membrane interaction: the differential scanning calorimetry technique on dimyristoylphosphatidylcholine multilamellar and unilamellar vesicles and the Langmuir-Blodgett technique on dimyristoylphosphatidylcholine monolayers. The results evidenced the strong antioxidant activity of U-74389G (especially in a membranous system) and its capability to interact with and be transported across model membranes. Thus one can speculate that U-74389G can act as scavenger of chain-propagating lipid peroxyl radicals within the membranes and may be able to protect not only cell membranes, but also intracellular components against peroxidative attack. Furthermore, also if there is no certain proof that the effect on the lipid packing order may play a key role in its antioxidant activity, the fluidifying effect on phospholipid bilayers of U-74389G favourably complements its free radical scavenging characteristics.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Amidines; Antioxidants; Bepridil; Biphenyl Compounds; Calorimetry, Differential Scanning; Dexamethasone; Free Radical Scavengers; Free Radicals; In Vitro Techniques; Linoleic Acid; Lipid Bilayers; Lipid Peroxidation; Oxidation-Reduction; Picrates; Pregnatrienes

Epidemiological evidence suggests an inverse relationship between dietary intake of flavonoids and cardiovascular risk. The biological activities of flavonoids are related to their antioxidative effects, but they also can be mutagenic, due to the prooxidant activity of the catechol pattern. To prevent these problems, we synthesized new flavonoids where one or two di-tert-butylhydroxyphenyl (DBHP) groups replaced catechol moiety at position 2 of the benzopyrane heterocycle. Two DBHP moieties can also be arranged in an arylidene structure or one DBHP fixed on a chalcone structure. Position 7 on the flavone and arylidene or position 4 on the chalcone was substituted by H, OCH(3), or OH. New structures were compared with quercetin and BHT in an LDL oxidation system induced by Cu(II) ions. Arylidenes and chalcones had the best activities (ED(50) = 0.86 and 0.21) compared with vitamin E, BHT, and quercetin (ED(50) = 10.0, 7. 4, and 2.3 microM). Activity towards stable free radical 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) was measured by log Z and ECR(50) parameters. Synthesized flavones proved to be poor DPPH radical scavengers, the activity increasing with the number of DBHP units. In contrast, arylidenes and chalcones were stronger DPPH radical scavengers (log Z > 3, 0.3 < ECR(50) < 2.12) than BHT (log Z = 0.75, ECR(50) = 12.56) or quercetin (log Z = 2.76, ECR(50) = 0.43). Unlike quercetin, synthesized compounds neither chelated nor reduced copper, proving that these new flavonoids had no prooxidant activity in vitro.

Topics: Amidines; Antioxidants; Bepridil; Biphenyl Compounds; Copper; Flavonoids; Free Radicals; Humans; In Vitro Techniques; Lipoproteins, LDL; Oxidants; Oxidation-Reduction; Picrates

The purpose of this study is to examine the relationship between the free radical scavenging activities and the chemical structures of tea catechins ((-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC)) and their corresponding epimers ((-)-gallocatechin gallate (GCG), (-)-gallocatechin (GC) and (+)-catechin ((+)-C)). With electron spin resonance (ESR) we investigated their scavenging effects on superoxide anions (O-.2) generated in the irradiated riboflavin system, singlet oxygen(1O2) generated in the photoradiation-hemoporphyrin system, the free radicals generated from 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. The results showed that the scavenging effects of galloylated catechins (EGCG and GCG) on the four free radicals were stronger than those of nongalloylated catechins (EGC, GC, EC, (+)-C), and the scavenging effects of EGC and GC were stronger than those of EC and (+)-C. Thus, it is suggested that the presence of the gallate group at the 3 position plays the most important role in their free radical-scavenging abilities and an additional insertion of the hydroxyl group at the 5' position in the B ring also contributes to their scavenging activities. Moreover, the corresponding phenoxyl radicals formed after the reaction with O-.2 were trapped by DMPO and the ESR spectra of DMPO/phenoxyl radical adducts were observed (aN=15.6 G and aHbeta=21.5 G). No significant differences were found between the scavenging effects of the catechins and their epimers when their concentrations were high. However, significant differences were observed at relatively low concentrations, and the lower their concentrations, the higher the differences. The scavenging abilities of GCG, GC and (+)-C were stronger than those of their corresponding epimers (EGCG, EGC and EC). The differences between their sterical structures played a more important role in their abilities to scavenge large free radicals, such as the free radicals generated from AAPH and the DPPH radical, than to scavenge small free radicals, such as O-.2 and 1O2, especially in the case with EGCG and GCG with more bulky steric hindrance.

Topics: Amidines; Antioxidants; Bepridil; Biphenyl Compounds; Catechin; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Isomerism; Oxidation-Reduction; Oxygen; Picrates; Singlet Oxygen; Structure-Activity Relationship; Superoxides; Tea

The mechanism of metal ion-catalyzed oxidative modification of apolipoprotein E (apoE) in human very-low-density lipoprotein (VLDL) and its inhibition by glycosaminoglycan (GAG) was investigated in vitro. The VLDL oxidation catalyzed by Cu2+ led to the lipid peroxidation, the formation of aggregates, and covalent modification of apoE. The modified apoE lost heparin-binding activity. These results suggest that the lipid peroxidation of VLDL and modification of apoE cause impairment of lipid uptake by cells and deposit the oxidized lipids in the tissues. The lipid peroxidation and oxidative modification of apoE in VLDL mediated by Cu2+ and an aqueous radical generator were suppressed by GAG, heparan sulfate, heparin, and chondroitin sulfate A, even though GAGs demonstrated no ability to scavenge alpha,alpha-diphenyl-beta-picrylhydrazyl radical. There were no relationships between inhibitory activity of GAGs in the VLDL oxidation and their number of sulfate groups which possess chelating activity of metal ion. Therefore, it can be considered that the inhibition of VLDL oxidation by GAGs is possibly due to the interaction between GAG and VLDL which bring about the steric hindrance, interference with the reaction between VLDL particle and the reactive oxygen species. These studies suggest that GAGs preserve the biological functions of apoE from oxidative stress.

Topics: Adult; Aldehydes; Alzheimer Disease; Amidines; Apolipoproteins E; Bepridil; Biphenyl Compounds; Chelating Agents; Cholesterol Esters; Chondroitin Sulfates; Copper Sulfate; Dextrans; Free Radical Scavengers; Glutathione; Glycosaminoglycans; Heparin; Hippocampus; Humans; Hydrogen-Ion Concentration; Lipid Peroxidation; Lipoproteins, VLDL; Male; Picrates; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances

Doxazosin is an antihypertensive drug that gives rise to 6- and 7-hydroxydoxazosin during hepatic metabolism. The structures of the hydroxymetabolites suggest that they may possess antioxidative properties. The aim of the present study was to examine whether doxazosin and 6- and 7-hydroxydoxazosin were able to scavenge free radicals and whether these compounds might protect low-density lipoprotein (LDL) against in vitro and ex vivo oxidation. Both 6- and 7-hydroxydoxazosin showed radical scavenging capacity as assessed by measuring scavenging of 1,1-diphenyl-2-picrylhydrazyl radicals. In vitro incubation with 10 microM 6- and 7-hydroxydoxazosin significantly reduced human mononuclear cell-mediated oxidation of LDL, measured as the formation of lipid peroxides and the relative electrophoretic mobility of LDL (to 10 and 6% of the control, respectively). Furthermore, formation of conjugated dienes in LDL during Cu2+-induced oxidation was significantly reduced in the presence of 5 microM 6- and 7-hydroxydoxazosin (to 28% of tmax [time to maximum] of control). However, treatment of hypertensive patients with increasing doses of doxazosin (from 1 to 8 mg/day) for 8 weeks altered neither Cu2+-catalyzed, 2,2'azobis-(2-amidinopropane hydrochloride)-initiated, nor cell-mediated oxidation of patient LDL ex vivo. Furthermore, the total antioxidative capacity of plasma was unaffected by treatment. In conclusion, the present study shows that 6- and 7-hydroxydoxazosin have radical scavenging properties and protect LDL against in vitro oxidation. However, treatment of hypertensive male subjects with increasing doses of doxazosin for 8 weeks did not affect ex vivo oxidation of LDL.

Topics: Adult; Aged; Amidines; Antihypertensive Agents; Antioxidants; Bepridil; Biphenyl Compounds; Copper; Doxazosin; Free Radical Scavengers; Humans; Hypertension; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Oxidants; Picrates

To determine the antioxidant activity of dietary quercetin (3,3',4', 5,7-pentahydroxyflavone) in the blood circulation, we measured the inhibitory effect of quercetin metabolites and their related derivatives on copper ion-induced lipid peroxidation of human low-density lipoprotein (LDL). Conjugated quercetin metabolites were prepared from the plasma of rat 1 h after oral administration of quercetin aglycone (40 micromol/rat). The rate of cholesteryl ester hydroperoxide (CE-OOH) accumulation and the rate of alpha-tocopherol consumption in mixtures of LDL solution (0.4 mg/ml) with equal volumes of this preparation were slower than the rates in mixtures of LDL with preparations from control rats. The concentrations of CE-OOH after 2 h oxidation in the mixtures of LDL with preparations of conjugated quercetin metabolites were significantly lower than those in the control preparation. It is therefore confirmed that conjugated quercetin metabolites have an inhibitory effect on copper ion-induced lipid peroxidation in human LDL. Quercetin 7-O-beta-glucopyranoside (Q7G) and rhamnetin (3,3',4', 5-tetrahydroxy-7-methoxyflavone) exerted strong inhibition and their effect continued even after complete consumption, similarly to quercetin aglycone. The effect of quercetin 3-O-beta-glucopyranoside (Q3G) did not continue after its complete consumption, indicating that the antioxidant mechanism of quercetin conjugates lacking a free hydroxyl group at the 3-position is different from that of the other quercetin conjugates. The result that 4'-O-beta-glucopyranoside (Q4'G) and isorhamnetin (3,4',5, 7-tetrahydroxy-3'-methoxyflavone) showed little inhibition implies that introduction of a conjugate group to the position of the dihydroxyl group in the B ring markedly decreases the inhibitory effect. The results of azo radical-induced lipid peroxidation of LDL and the measurement of free radical scavenging capacity using stable free radical, 1,1,-diphenyl-2-picrylhydrazyl, demonstrated that the o-dihydroxyl structure in the B ring is required to exert maximum free radical scavenging activity. It is therefore likely that conjugation occurs at least partly in positions other than the B ring during the process of metabolic conversion so that the inhibitory effect of dietary quercetin is retained in blood plasma after absorption.

Topics: Amidines; Animals; Antioxidants; Bepridil; Biphenyl Compounds; Cholesterol Esters; Copper Sulfate; Cysteine; Free Radical Scavengers; Free Radicals; Humans; Kinetics; Lipid Peroxidation; Lipoproteins, LDL; Male; Models, Chemical; Oxidants; Oxidation-Reduction; Picrates; Quercetin; Rats; Rats, Wistar; Vitamin E

The antioxidant activities of methanol and ethyl ether extracts obtained from Thymus zygis, collected during the flowering or non-flowering period, were evaluated and compared. To investigate this potential, extracts were tested on their capacity to react with diphenylpicrylhydrazyl (DPPH) in a homogeneous medium, and to inhibit Fe2+/ascorbate-induced membrane lipid peroxidation, as estimated by the formation of thiobarbituric acid-reactive substances (TBARS). Although methanol extracts reduce DPPH radicals more efficiently than ethyl ether extracts, suggesting a potent radical scavenger activity, the ethyl ether extracts were found to be most active in inhibiting lipid peroxidation in sarcoplasmic reticulum (SR) membranes. In addition, both extracts present peroxyl and superoxide radical scavenging activities. Peroxyl radicals were generated by the water soluble 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) azoinitiator, and the scavenging activities of the extracts were measured by the inhibition of cis-parinaric acid (PnA) fluorescence decay in SR. Superoxide radicals were generated either by an enzymatic or a non-enzymatic system, and the scavenger ability was evaluated by the inhibition of nitroblue tetrazolium reduction. Methanolic extracts are more potent as scavengers of peroxyl and superoxide radicals than the ethyl ether extracts. Apparently, there is a relationship between antioxidant potency and the total phenolic groups content in each extract.

Topics: Amidines; Antioxidants; Bepridil; Biphenyl Compounds; Fluorometry; Free Radical Scavengers; Free Radicals; Indicators and Reagents; Lipid Peroxidation; Peroxides; Phenols; Picrates; Plant Extracts; Plants, Medicinal; Superoxides

The antioxidant effect of melatonin on LDL oxidation was studied in vitro using either a thermolabile initiator or copper ions to induce lipid peroxidation. Loading of LDL with melatonin showed only weak protection against oxidative damage as compared to alpha-tocopherol. In the presence of high concentrations of melatonin (1000 mol/mol LDL) in the medium a clear protective effect was found during lag- and propagation phase, albeit weaker than after loading with alpha-tocopherol. It is concluded that melatonin is not incorporated into LDL in sufficient concentrations to prevent lipid peroxidation effectively. When melatonin is present in the incubation medium during oxidation, a partitioning equilibrium between aqueous and lipid phase is established. Only under these conditions can melatonin act as a chain breaking antioxidant. The concentrations required, however, are far beyond those found in human plasma. Therefore, the data in this study do not support a direct physiological relevance of melatonin as an antioxidant in lipid peroxidation processes.

Topics: Amidines; Antioxidants; Bepridil; Biphenyl Compounds; Copper Sulfate; Free Radicals; Humans; Lipid Peroxidation; Lipoproteins, LDL; Melatonin; Picrates; Vitamin E

Homocysteine is an independent risk factor for cardiovascular diseases. The mechanisms by which elevated plasma concentrations of homocysteine are related to the pathogenesis of atherosclerosis are not fully understood. To examine whether homocysteine is implicated in atherogenesis through the modification of low density lipoprotein (LDL), the effect of homocysteine on the oxidation of LDL was studied by three different oxidation systems. Thus, LDL was subjected to Cu(2+)-catalyzed, azo compound-initiated, and peripheral blood mononuclear cell-mediated oxidative modification. The extent of modification was assessed by measuring the formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, and the relative electrophoretic mobility. Homocysteine at a normal plasma concentration (6 microM) showed no effect, whereas a concentration corresponding to moderate hyperhomocysteinemia (25 microM) or to concentrations seen in homocystinuria patients (100, 250, and 500 microM) protected LDL from modification of the lipid as well as of the protein moiety. One exception was observed: when the oxidation was initiated by copper ions, homocysteine at concentrations 6 and 25 microM stimulated the lipid peroxidation of LDL to a small, but statistically significant extent. High concentrations of homocysteine showed antioxidative properties as long as the thiol groups were intact, thereby delaying the onset of the oxidation. The 1,1-diphenyl-2-picrylhydracyl radical test demonstrated that homocysteine at concentrations > or = 50 microM possessed marked free radical scavenging capacity. Finally, LDL isolated from two patients with homozygous homocystinuria showed similar extent of Cu(2+)-catalyzed oxidation as LDL from a group of healthy control subjects. Taken together, our data suggest that low concentrations of homocysteine in the presence of copper ions may enhance the lipid peroxidation of LDL, whereas high concentrations of homocysteine may protect LDL against oxidative modification in the lipid as well as in the protein moiety. Thus, homocysteine-induced atherosclerosis may be explained by mechanisms other than oxidative modification of low density lipoprotein.

Topics: Adolescent; Adult; Amidines; Arteriosclerosis; Azo Compounds; Bepridil; Biphenyl Compounds; Child; Copper; Female; Free Radical Scavengers; Homocysteine; Homocystinuria; Humans; Leukocytes, Mononuclear; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Picrates

The effects of paracetamol and sodium salicylate on the susceptibility of LDL to oxidative modification were studied. LDL was subjected to Cu(2+)-, azo compound-, or peripheral blood mononuclear cell-initiated oxidation in the absence and presence of paracetamol and salicylate. Paracetamol (100 mumol/L; 25 micrograms LDL/mL) reduced the rate of formation of conjugated dienes and the amount of conjugated dienes formed during Cu(2+)-induced oxidation by 67% and 58%, respectively. Paracetamol (400 mumol/L; 100 micrograms LDL/mL) reduced the generation of lipid peroxides during Cu(2+)-induced oxidation by 43% (P < .05), the relative electrophoretic mobility in agarose gels by 16% (P < .05), and the amount of oxidized LDL taken up by J774 macrophages by 22% (P < .05). Paracetamol (100 mumol/L; 100 micrograms LDL/mL) reduced the 2,2'-azobis-(2-amidinopropane hydrochloride)-initiated lipid peroxidation by 70% (P < .05) and the relative electrophoretic mobility by 34% (P < .05). Paracetamol (100 mumol/L; 100 micrograms LDL/mL) reduced the amount of lipid peroxides generated in LDL during mononuclear cell-mediated oxidation by 69% (P < .01) and the relative electrophoretic mobility by 38% (P < .01). In comparison, 10 mumol/L alpha-tocopherol reduced the amount of lipid peroxides formed during cellular LDL oxidation and the relative electrophoretic mobility by 52% and 65%, respectively (P < .05). In the absence of paracetamol, SOD and catalase inhibited the modification of LDL (P < .05), suggesting that superoxide anions and hydrogen peroxide might be involved in the cell-mediated modification pathway. In the presence of paracetamol, SOD showed no additional inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetaminophen; Amidines; Bepridil; Biphenyl Compounds; Catalase; Copper; Free Radical Scavengers; Humans; Kinetics; Leukocytes, Mononuclear; Lipid Peroxidation; Lipoproteins, LDL; Picrates; Salicylates; Salicylic Acid; Superoxide Dismutase