MACROMOLECULAR THEORY AND SIMULATIONS, Issue 9 2007
Hidetaka Tobita
Abstract Controlled/living radical polymerization systems in which the active period is extremely small, ,A,,,1, such as the cases of stable free radical mediated polymerization (or nitroxide mediated polymerization) and atom transfer radical polymerization, are considered theoretically. The polymerization rate, Rp, for such systems increases by lowering the trapping agent concentration [X]. When the polymerization is conducted inside small particles, Rp decreases with D below the diameter Dp,SMC at which a single molecule concentration (SMC) is equal to [X]bulk. On the other hand, when the average number of trapping agents in a particle is smaller than about 10, the fluctuation of nX among particles is significant, which leads to a larger Rp than in the cases where all particles contain the same nX. Because of the effects of SMC and fluctuation, Rp may show an acceleration window, Dp,SMC,<,Dp,<,Dp,Fluct where Rp is slightly larger than that in bulk. [source]

Hybrid Magnetic Materials Based on Nitroxide Free Radicals and Extended Oxalato-Bridged Bimetallic Networks

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 2 2005
Antonio Alberola
Abstract A series of hybrid organic-inorganic magnets of formula p -rad[MIICr(ox)3] [M = Mn (1), Co (2), Ni (3), Zn (4)] and m -rad[MIICr(ox)3] [M = Mn (5), Co (6)], in which N -methylpyridinium cations bearing a nitronyl nitroxide moiety in positions 3 (m -rad) or 4 (p -rad) of the pyridine ring coexist with the 2D honeycomb-like oxalato-bridged bimetallic lattice, has been prepared and studied by AC and DC magnetic susceptibility measurements and EPR spectroscopy. In general, the physical properties of these magnets are not altered significantly by the insertion of the nitronyl nitroxide radicals although these paramagnetic molecules seem to interact weakly with the inorganic network as demonstrated by EPR spectroscopy. Some differences can also be observed between the p -rad and m -rad series, i.e. m -rad derivatives have smaller values for the critical temperatures and coercive fields. We also report on the X-ray crystal structures and magnetic properties of p -rad[Mn(H2O)Cr(ox)3]·2H2O (7) and m -rad[Mn(H2O)2Cr(ox)3]·2H2O (8), two extended oxalato-bridged compounds with new topologies. Compound 7 is antiferromagnetic and its structure is a 3D achiral lattice in which zigzag ferromagnetic MnCr chains (J/k = +0.8 K) are interconnected to form hellicoidal hexagonal channels with the cationic free radicals residing in the free space. Compound 8, however, exhibits a ladder-like structural pattern with competing magnetic interactions and paramagnetic behaviour down to low temperatures. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source]

Free Radicals in Wheat Seeds Studied by Electron Spin Resonance

JOURNAL OF FOOD SCIENCE, Issue 6 2002
F. Szöcs
ABSTRACT: We used electron spin resonance (ESR) to investigate free radicals in wheat seeds in air or under vacuum in relation to annealing temperature. Annealing in the 100 to 200 °C range resulted in concentration increases of free radicals in samples. A greater increase was observed for experiments carried out in air than for those under vacuum. Most free radicals occurred in the grain surface layer. The bran contained a concentration of free radicals 100 times greater than that of the white grain portion. The reaction of stable free radicals in bran was also studied during thermal decomposition of dibenzoyl peroxide at high pressure. They reacted with shortlived peroxyl radicals in bran to produce a nonradical product. [source]

Scavenging Free Radicals To Preserve Enhancement and Extend Relaxation Times in NMR using Dynamic Nuclear Polarization,

ANGEWANDTE CHEMIE, Issue 35 2010
Pascal Miéville
Länger leben dank Vitamin,C: N -Oxid-Radikale, die weithin zur dynamischen Kernpolarisation eingesetzt werden, können beim Auflösen durch Abfangreagentien wie Natriumascorbat (Vitamin,C) reduziert werden, wodurch Polarisierungsverluste während des Transfers vermieden und transversale wie longitudinale Relaxationszeiten in NMR-spektroskopischen Experimenten verlängert werden (siehe Bild). [source]

Free Radicals in Biology and Medicine: From Inflammation to Biotechnology

BIOFACTORS, Issue 1-4 2006
Okezie I. Aruoma
No abstract is available for this article. [source]

New Tetrahydro-1,2,4,5-tetrazinan-3-ones and Oxoverdazyl Free Radicals.

CHEMINFORM, Issue 52 2006
M. John Plater
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source]

Gene delivery of Cu/Zn-superoxide dismutase improves graft function after transplantation of fatty livers in the rat

HEPATOLOGY, Issue 6 2000
Thorsten G. Lehmann
Oxygen-derived free radicals play a central role in reperfusion injury after organ transplantation, and fatty livers are particularly susceptible. Endogenous radical scavengers such as superoxide dismutase (SOD) degrade these radicals; however, SOD is destroyed rapidly when given exogenously. Therefore, an adenoviral vector encoding the Cu/Zn-SOD gene (Ad.SOD1) was used here to test the hypothesis that organ injury would be reduced and survival increased in a rat model of transplantation of fatty livers. Donors received chow diet (untreated), high-fat diet, or ethanol-containing high-fat diet. Some of the ethanol-fed donors were infected either with the gene lacZ encoding bacterial ,-galactosidase (Ad.lacZ), or Ad.SOD1. After liver transplantation, SOD activity and protein expression in liver, survival, histopathology, release of transaminases, free radical adducts in bile, and activation of NF-,B, I,B kinase (IKK), Jun-N-terminal kinase (JNK), and TNF, were evaluated. Ad.SOD1 treatment increased survival dramatically, blunted transaminase release, and reduced necrosis and apoptosis significantly. Free radical adducts were increased two-fold in the ethanol group compared with untreated controls. Ad.SOD1 blunted this increase and reduced the activation of NF-,B. However, release of TNF, was not affected. Ad.SOD1 also blunted JNK activity after transplantation. This study shows that gene therapy with Ad.SOD1 protects marginal livers from failure after transplantation because of decreased oxygen radical production. Genetic modification of fatty livers using viral vectors represents a new approach to protect marginal grafts against primary nonfunction. [source]

Free radical,scavenging activity and DNA damaging potential of auxins IAA and 2-methyl-IAA evaluated in human neutrophils by the alkaline comet assay

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2010
Branka Salopek-Sondi
Auxins, of which indole-3-acetic acid (IAA) is the most widespread representative, are plant hormones. In addition to plants, IAA also naturally occurs in humans in micromolar concentrations. In the presence of peroxidase, indolic auxins are converted to cytotoxic oxidation products and have thus been proposed for use in gene-directed enzyme/prodrug tumor therapy. Since data on the genotoxicity of IAA and its derivatives are not consistent, here we investigate the early DNA damaging effects (2-h treatment) of the auxins, IAA, and 2-methyl-indole-3-acetic acid (2-Me-IAA) by the alkaline comet assay and compare them with their free radical,scavenging activity measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Human neutrophils are chosen as the test system since they possess inherent peroxidase activity. The results of the comet assay indicate an increase in DNA damage in a dose-dependent manner up to 1.00 mM of both auxins. Generally, IAA applied in the same concentration had greater potential to damage DNA in human neutrophils than did 2-Me-IAA. The genotoxicities of the two examined auxins are negatively correlated with their antioxidant activities, as measured by the DPPH assay; 2-Me-IAA showed a higher antioxidant capacity than did IAA. We assume that differences in the molecular structure of the tested auxins contributed to differences in their metabolism, in particular, with respect to interactions with peroxidases and other oxidative enzymes in neutrophils. However, the exact mechanisms have to be elucidated in future studies. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:165,173, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20323 [source]

Free radical 4-nitrophenylation of thieno[2,3- b]pyridine.

JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2001
Part 2: Isolation, structural studies of three samples of mono (4-nitrophenyl) products; relative yields of the five possible isomers
From the crude mixtures of isomeric 4-nitrophenylthieno[2,3- b]pyridines (3) previously reported [1] were isolated three analytically pure samples, viz. the 2-isomer (yellow needles, mp 258°, 3a), the 6-isomer (red prisms, mp 182°, 3e), and a ternary mixture of the 2-, 3-, and 4-isomers (orange needles, mp 213°, 3a:3b:3c = 1.3:1.0:0.5). The 258° compound was identified as either 3a or 3b by its 1H nmr spectrum and definitively as the former by its x-ray crystallographic analysis. The isomeric identities of the 182° and 213° samples were established from their 1H nmr spectra only. No 5-isomer (3d) was identified. Semi-quantitatively, relative isomeric yields fit the pattern 2- (64%)>>6- (14%),3- (12%)>4- (6%),5-(,4%). Crystallographic data for 3a are presented. [source]

Free radical and nitroxide mediated polymerization of hydroxy,functional acrylates prepared via lipase,catalyzed transacylation reactions

JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 12 2010
Dragos Popescu
Abstract 3-Hydroxypropyl acrylate, 4-hydroxybutyl acrylate, 2-methyl-3-hydroxypropyl acrylate, 2-hydroxypropyl acrylate, neopentyl glycol acrylate, glyceryl acrylate, and dihydroxyhexyl acrylate were prepared via transacylation reaction of methyl acrylate with diols and triols catalyzed by Candida antarctica lipase B. After removal of the enzyme by filtration and the methyl acrylate by distillation, the monomers were polymerized via free radical polymerization (FRP) with azobisisobutyronitrile as initiator and nitroxide mediated polymerization (NMP) employing BlocbuilderÔ alkoxyamine initiator and SG-1 free nitroxide resulting in hydroxy functional poly(acrylates). The NMP kinetics are discussed in detail. In addition, the polymers obtained by FRP and NMP are compared and the results are related to the amount of bisacrylates that are present in the initial monomer mixtures resulting from the transacylation reactions. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2610,2621, 2010 [source]

Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity,

ARTHRITIS & RHEUMATISM, Issue 7 2010
Gangduo Wang
Objective Free radical,mediated reactions have been implicated as contributors in a number of autoimmune diseases, including systemic lupus erythematosus (SLE). However, the potential for oxidative/nitrosative stress to elicit an autoimmune response or to contribute to disease pathogenesis, and thus be useful when determining a prognosis, remains largely unexplored in humans. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with SLE. Methods Sera from 72 SLE patients with varying levels of disease activity according to the SLE Disease Activity Index (SLEDAI) and 36 age- and sex-matched healthy controls were evaluated for serum levels of oxidative/nitrosative stress markers, including antibodies to malondialdehyde (anti-MDA) protein adducts and to 4-hydroxynonenal (anti-HNE) protein adducts, MDA/HNE protein adducts, superoxide dismutase (SOD), nitrotyrosine (NT), and inducible nitric oxide synthase (iNOS). Results Serum analysis showed significantly higher levels of both anti,MDA/anti,HNE protein adduct antibodies and MDA/HNE protein adducts in SLE patients compared with healthy controls. Interestingly, not only was there an increased number of subjects positive for anti-MDA or anti-HNE antibodies, but also the levels of both of these antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were ,6 as compared with SLE patients with lower SLEDAI scores (SLEDAI score <6). In addition, a significant correlation was observed between the levels of anti-MDA or anti-HNE antibodies and the SLEDAI score (r = 0.734 and r = 0.647, respectively), suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD and higher levels of iNOS and NT compared with healthy control sera. Conclusion These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis. [source]

Free radicals, diabetes and endothelial dysfunction

DIABETES OBESITY & METABOLISM, Issue 4 2002
U. Bayraktutan
First page of article [source]

Increased susceptibility to oxidative stress as a proximate cost of reproduction

ECOLOGY LETTERS, Issue 5 2004
Carlos Alonso-Alvarez
Abstract In iteroparous species high investment in current reproduction is usually paid in terms of reduced future reproduction and increased mortality. However, the proximal mechanisms of these costs remain poorly understood. Free radicals arising as by-products of normal metabolic activities have deleterious effects on cellular proteins, lipids and DNA, and this phenomenon is known as oxidative stress. Since reproduction is an energetically demanding activity, which increases both basal and field metabolic rates, one could expect that breeding effort generates an oxidative stress whose strength depends on the availability and efficiency of antioxidant defences. In agreement with this prediction, we show here for the first time that reproduction decreases antioxidant defences, illustrating that oxidative stress represents a cost of reproduction. We suggest that increased susceptibility to oxidative stress might be a general proximal connection between reproduction and survival underlying other mechanistic links previously acknowledged. [source]

Free radicals, antioxidants, and soil organic matter recalcitrance

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 2 2006
D. L. Rimmer
Summary Highly reactive, and potentially damaging, free radicals are readily generated in our oxygen-rich environment, and are ubiquitous in biological systems. However, plants and animals have evolved protection against them with a range of antioxidant molecules, such as vitamins C and E, many of which are phenolic compounds. These stop the destructive chain reaction of free radical formation by being transformed into unreactive, stable free radicals. The biodegradation of food involves oxidation by free radicals, and is retarded by antioxidants. Similarly, the biodegradation of plant residues in soils involves free radicals; so the questions arise: (i) do soils have antioxidants, and (ii) what function might they have? The evidence suggests that they probably do have antioxidants. First, plant and animal remains added to soils will contain antioxidants. These are likely to persist for a time, particularly tannins, which are polyphenolic compounds with known antioxidant properties and which are relatively resistant to degradation. Second, studies using electron spin resonance spectroscopy have shown that humic materials contain stable semiquinone free radicals, and that their concentration increases as humification progresses. These semiquinone species are most likely to be derived from the reaction of phenolic compounds with reactive radicals. If this is the case, the phenolics are acting as antioxidants, because they are scavenging the reactive free radicals and terminating the oxidative chain reaction responsible for soil organic matter (SOM) degradation. Thus the soil's antioxidant capacity could control the rate of breakdown of organic matter in the more labile pools and could provide a chemical mechanism for the recalcitrance of SOM. Current available evidence for the nature of the recalcitrant pool in SOM is discussed in the light of this hypothesis, and the experimental approaches necessary for testing it are outlined. [source]

Diabetes, oxidative stress, and antioxidants: A review

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2003
A. C. Maritim
Abstract Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:24,38, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10058 [source]

A new source of aging?

JOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2009
Helen Knaggs MD
Summary There has been a considerable increase in understanding how skin ages, along with significant progress toward the correction and prevention of the visible signs of aging. However, there are still many unknown factors regarding why we age , and why we all seem to age differently. An area of high interest is the biological or intrinsic processes that affect our appearance over time. This article describes a recent discovery of a membrane bound enzyme proven to be present in skin and increases its activity as biological age increases. The enzyme is located on the external surface of both fibroblast and keratinocytes, and generates free radicals. Therefore, as we age there appears to be a biological mechanism that further increases the production of free radicals. Additionally, there appears to be a relationship between activity of the enzyme and appearance. Data showed that subjects who look younger than their biological age had lower enzyme activity and conversely, subjects who looked older than their biological age had higher enzyme activity. Free radicals are believed to be a major contributing factor in the production of fine lines and wrinkles by destroying the collagen and elastin network keeping skin supple and firm. [source]

Free radical scavengers are more effective than indomethacin in the prevention of experimentally induced heterotopic ossification

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2007
L.C. Vanden Bossche
Abstract The pathogenesis of heterotopic ossification is still unclear and the preventive therapies are usually insufficient. The present study was designed to investigate the possible preventive effect of free radical scavengers on the development of experimentally induced heterotopic ossification in a rabbit model and to compare free radical scavengers with indomethacin to determine whether they act synergistically. A standard immobilization,manipulation model was used to induce heterotopical ossification in the hind legs of 40 1-year-old female New Zealand albino rabbits. The animals were divided into four groups and received daily either placebo, a free radical scavenger cocktail [allopurinol and N -acetylcysteine (A/A)], indomethacin or the combination of A/A and indomethacin in a randomized double-blind fashion. Every 4 days an X-ray was taken and the thickness and length of new bone formation was measured at the thigh. A marked statistically significant difference was found between the four groups. In the groups that received A/A, either alone or combined with indomethacin, an inhibition of bone growth, both in thickness and in length was demonstrated. In this experimental model free radical scavengers had a superior inhibitory effect on heterotopic ossification than indomethacin. Free radicals could play an important role in the pathogenesis of heterotopic ossification. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:267,272, 2007 [source]

Oxidative stress and apoptosis: Impact on cancer therapy

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2007
Tomris Ozben
Abstract It is well established that some chemotherapeutic agents and radiation therapy generate reactive oxygen species (ROS) in patients during cancer therapy. Free radicals, particularly ROS have been proposed as common mediators for apoptosis. Recent studies have demonstrated that the mode of cell death depends on the severity of the oxidative damage. This review will address some of the current paradigms of oxidative stress, and antioxidants on apoptosis, and discuss the potential mechanisms by which oxidants can regulate apoptotic pathways. It will also review new developments in eliminating cancer cells by selectively inducing apoptosis. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2181,2196, 2007 [source]

Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenols

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2006
Zhi Zhong
The immunosuppressants ciclosporin (cyclosporin A, CsA) and tacrolimus can cause severe nephrotoxicity. Since CsA increases free radical formation, this study investigated whether an extract from Camellia sinensis, which contains several polyphenolic free radical scavengers, could prevent nephrotoxicity caused by CsA and tacrolimus. Rats were fed powdered diet containing polyphenolic extract (0-0.1%) starting 3 days before CsA or tacrolimus. Free radicals were trapped with ,-(4-pyridyl-1-oxide)- N - tert -butylnitrone (POBN) and measured using an electron spin resonance spectrometer. Both CsA and tacrolimus decreased glomerular filtration rates (GFR) and caused tubular atrophy, vacuolization and calcification and arteriolar hyalinosis, effects that were blunted by treatment with dietary polyphenols. Moreover, CsA and tacrolimus increased POBN/radical adducts in urine nearly 3.5 fold. Hydroxyl radicals attack dimethyl sulfoxide (DMSO) to produce a methyl radical fragment. Administration of CsA or tacrolimus with 12C-DMSO produced a 6-line spectrum, while CsA or tacrolimus given with 13C-DMSO produced a 12-line ESR spectrum, confirming formation of hydroxyl radicals. 4-Hydroxynonenal (4-HNE), a product of lipid peroxidation, accumulated in proximal and distal tubules after CsA or tacrolimus treatment. ESR changes and 4-HNE formation were largely blocked by polyphenols. Taken together, these results demonstrate that both CsA and tacrolimus stimulate free radical production in the kidney, most likely in tubular cells, and that polyphenols minimize nephrotoxicity by scavenging free radicals. [source]

Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation

JOURNAL OF PINEAL RESEARCH, Issue 4 2009
Zhanqing Li
Abstract:, Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine,Tryptophan,Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39,71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity. [source]

Synthesis and characterization of poly(methyl methacrylate)/casein nanoparticles with a well-defined core-shell structure

JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 21 2003
Junmin Zhu
Abstract Well-defined, core-shell poly(methyl methacrylate) (PMMA)/casein nanoparticles, ranging from 80 to 130 nm in diameter, were prepared via a direct graft copolymerization of methyl methacrylate (MMA) from casein. The polymerization was induced by a small amount of alkyl hydroperoxide (ROOH) in water at 80 °C. Free radicals on the amino groups of casein and alkoxy radicals were generated concurrently, which initiated the graft copolymerization and homopolymerization of MMA, respectively. The presence of casein micelles promoted the emulsion polymerization of the monomer and provided particle stability. The conversion and grafting efficiency of the monomer strongly depended on the type of radical initiator, ROOH concentration, casein to MMA ratio, and reaction temperature. The graft copolymers and homopolymer of PMMA were isolated and characterized with Fourier transform infrared spectroscopy and differential scanning calorimetry. The molecular weight determination of both the grafted and homopolymer of PMMA suggested that the graft copolymerization and homopolymerization of MMA proceeded at a similar rate. The transmission electron microscopic image of the nanoparticles clearly showed a well-defined core-shell morphology, where PMMA cores were coated with casein shells. The casein shells were further confirmed with a zeta-potential measurement. Finally, this synthetic method allowed us to prepare PMMA/casein nanoparticles with a solid content of up to 31%. Thus, our new process is commercially viable. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3346,3353, 2003 [source]

Alcohol Metabolism: Role in Toxicity and Carcinogenesis

ALCOHOLISM, Issue 2 2003
Thomas M. Badger
This article contains the proceedings of a symposium at the 2002 RSA Meeting in San Francisco, organized and co-chaired by Thomas M. Badger, Paul Shih-Jiun Yin, and Helmut Seitz. The presentations were (1) First-pass metabolism of ethanol: Basic and clinical aspects, by Charles Lieber; (2) Intracellular CYP2E1 transport, oxidative stress, cytokine release, and ALD, by Magnus Ingelman-Sundberg; (3) Pulsatile ethanol metabolism in intragastric infusion models: Potential role in toxic outcomes, by Thomas M. Badger and Martin J.J. Ronis; (4) Free radicals, adducts, and autoantibodies resulting from ethanol metabolism: Role in ethanol-associated toxicity, by Emanuele Albano; and (5) Gastrointestinal metabolism of ethanol and its possible role in carcinogenesis, by Helmut Seitz. [source]

EPR study of nitroxides formed from the reaction of nitric oxide with photolyzed amides

MAGNETIC RESONANCE IN CHEMISTRY, Issue 9 2003
Fan Wang
Abstract Free radicals generated from UV irradiation of simple aliphatic amides in anaerobic and nitric oxide (NO)-saturated liquid mixtures or solutions gave EPR spectra of nitroxides. The application of isotopic effects to EPR spectra and the generation of radicals by transient radical attack on substrate molecules or by photolysing amine or acetoin were used to help identify photochemically produced radicals from the amides. The aliphatic amides used were formamide, acetamide and their N -methyl- or deuterium-substituted derivatives. Transient radicals used to attack the amides via hydrogen-atom abstraction were generated from the initiator AIBN or AAPH. The observation of various nitroxides indicates the reactivity of NO for trapping acyl, carbamoyl and other carbon-centered radicals. Possibly mechanistic pathways diagnosed with this trap are proposed. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Curcumin and the cellular stress response in free radical-related diseases

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 9 2008
Vittorio Calabrese
Abstract Free radicals play a main pathogenic role in several human diseases such as neurodegenerative disorders, diabetes, and cancer. Although there has been progress in treatment of these diseases, the development of important side effects may complicate the therapeutic course. Curcumin, a well known spice commonly used in India to make foods colored and flavored, is also used in traditional medicine to treat mild or moderate human diseases. In the recent years, a growing body of literature has unraveled the antioxidant, anticarcinogenic, and antinfectious activity of curcumin based on the ability of this compound to regulate a number of cellular signal transduction pathways. These promising data obtained in vitro are now being translated to the clinic and more than ten clinical trials are currently ongoing worldwide. This review outlines the biological activities of curcumin and discusses its potential use in the prevention and treatment of human diseases. [source]

Altered anti-oxidant status and increased lipid peroxidation in marasmic children

PEDIATRICS INTERNATIONAL, Issue 3 2000
M Mansur Tatli
Abstract Background: Protein energy malnutrition (PEM) is a common pediatric health problem in developing countries. Although the clinical features of PEM are well known, its pathophysiology is still unclear. Free radicals have been implicated in pathogenesis of PEM. In the present study, oxidant/anti-oxidant status in marasmus was investigated. Methods: Red cell glutathione, glutathione peroxidase and superoxide dismutase and their related cofactors, serum selenium and copper, were studied in marasmic and control children. Serum lipid peroxidation was also evaluated to assess oxidative stress. Results: The red cell glutathione levels and glutathione peroxidase activities were found to be significantly lower in the marasmic children than in the controls. Red cell superoxide dismutase (SOD) activity was not different between two groups. Serum selenium and copper concentrations were significantly lower in the marasmic children than in the control subjects. The malondialdehyde concentration, which is an index of lipid peroxidation, was significantly higher in the marasmic group compared with the controls. Conclusion: The anti-oxidant defense system was affected in marasmic children. Reduced anti-oxidant status and increased oxidative stress occurs in marasmic children. [source]

Possible biphasic changes of free radicals in ethylene glycol-induced nephrolithiasis in rats

BJU INTERNATIONAL, Issue 9 2000
H.S. Huang
Objective To evaluate the possible role of free radicals in nephrolithiasis in rats induced by ethylene glycol, and to examine the correlation between the urinary enzymes N-acetyl-,-glucosaminidase (NAG), ,-galactosidase (GAL) and neutral endopeptidase (NEP), and free radical production. Materials and methods Hyperoxaluria was produced in male Wistar rats by adding ethylene glycol to their drinking water. After 7, 21 and 42 days of treatment, urinary oxalate, creatinine clearance and urinary enzymes (NAG, GAL and NEP) were measured. The nitroblue tetrazolium perfusion method was used to locate the sites of free-radical production. Ultrasensitive chemiluminescence was used to directly measure the production of reactive oxygen species (ROS) in vivo. Vitamin E and potassium citrate were fed to rats, in addition to ethylene glycol, to assess their effects on free radical production. Results Urinary oxalate increased significantly and was associated with an increase in NAG and GAL at all sample times. However, urinary NEP activity was unchanged on day 7, although there was four times as much NEP on days 21 and 42 than in the control groups. Formazan particles in the renal cortex were scored as 3+ to 4+ in rats treated for 7 days with ethylene glycol. Blood ROS levels were also higher in this group than in the controls (P < 0.01). After vitamin E and potassium citrate treatment, blood ROS levels were lower than in rats treated with ethylene glycol alone. Conclusion Free radicals may be produced in the early stages of nephrolithiasis in rats fed with ethylene glycol. Free radicals occurred mainly in blood and might be associated with NEP inactivation. [source]

TOCOTRIENOL OFFERS BETTER PROTECTION THAN TOCOPHEROL FROM FREE RADICAL-INDUCED DAMAGE OF RAT BONE

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005
NS Ahmad
SUMMARY 1.,Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or ,-tocopherol acetate in Wistar rats. 2.,The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and ,-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure ,-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3.,Supplementation with the palm oil tocotrienol mixture or ,-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of ,-tocopherol acetate (P < 0.05). 4.,Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of ,-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes. [source]

Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinoma

DISEASES OF THE ESOPHAGUS, Issue 2 2008
T. Kaur
SUMMARY., The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course. [source]

Development of spray- and freeze-dried high-concentration sesamol emulsions and antioxidant evaluation in fibroblasts and UV-exposed rat skin slices

DRUG DEVELOPMENT RESEARCH, Issue 5 2008
Juliana Alencar
Abstract Dry sesamol emulsions were synthesized from several combinations of saccharose with hydroxypropylmethylcellulose (HPMC) or sodium caseinate (SC) using spray-drying techniques at 120° to 180°C, or freeze-drying. On the basis of physical characteristics such as droplet size distribution, residual moisture, and microscopic structure, the best material was obtained when spray-drying was applied at either 150° or 180°C with SC or HPMC as excipients, respectively. The extent to which the antioxidant properties of free sesamol towards a set of free radicals (galvinoxyl, diphenylpicrylhydrazyl, superoxide, and hydroxyl) were altered in the starting and reconstituted liquid emulsions submitted to normal storage or pre-exposed to a flux hydroxyl radicals was investigated. Emulsions were further evaluated for their antioxidant properties in cultured 3T3 murine fibroblasts and in an ex vivo model of ultraviolet irradiated rat skin. It was found that, in the material having the best physical properties, encapsulation was decisive in: (1) improving the overall antioxidant behavior of reconstituted versus starting liquid emulsions: (2) sparing sesamol consumption due to free radical attack; and (3) significantly protecting cells and skin against free radical- or irradiation-induced enzymatic release and/or lipid peroxidation. Demonstrating a high activity at high dilutions where interactions of excipient become negligible, the new emulsions could be of great interest in sesamol-based pharmacology or topical applications. Drug Dev Res 69:251,266, 2008. © 2008 Wiley-Liss, Inc. [source]

Thymol analogues with antioxidant and L-type calcium current inhibitory activity

DRUG DEVELOPMENT RESEARCH, Issue 4 2005
Ai-Yu Shen
Abstract Thymol is a natural product, which has antioxidant activity. 4-Morpholinomethyl-2-isopropyl-5-methylphenol (THMO), and 4-Pyrrolidinomethyl-2-isopropyl- 5-methylphenol (THPY) were synthesized by reacting thymol with formaldehyde and, respectively, morpholine or pyrrolidine. Since there is a relationship between the antioxidative status and incidence of human disease, anti-superoxidation, free radical scavenger activity, and anti-lipid peroxidation of the thymol analogues were determined by xanthine oxidase inhibition, cytochrome C system with superoxide anion releasing with formyl-Met-Leu-Phe (fMLP)/cytochalasin (CB) or phorbol myristate acetate (PMA) activating pathway in human neutrophils. All compounds studied had antioxidant activity. Mannich bases derived from thymol were generally found to be more potent compounds than thymol. THMO demonstrated the greatest antioxidant activity with IC50 values for xanthine oxidase inhibition and anti-lipid peroxidation being 21±2.78 and 61.29±5.83 µM, respectively. Moreover, since oxidative stress by free radical regulates the activity of L-type Ca2+ channel, the whole-cell configuration of the patch-clamp technique was used to investigate the effect of THMO upon ionic currents within NG108-15 cells. THMO (10 µM) suppressed the peak amplitude of L-type Ca2+ inward current (ICa,L), indicating that the antioxidative potential of the thymol analogues might be related to calcium current inhibition. The present studies suggest that THMO-dependent antioxidant and calcium ion current inhibition activity may be useful in treating free radical-related disorders. Drug Dev Res 64:195,202, 2005. © 2005 Wiley-Liss, Inc. [source]