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Antioxidant N (antioxidant + n)
Selected AbstractsVoltammetric Antioxidant Analysis in Mineral Oil Samples Immobilized into Boron-Doped Diamond Micropore Array ElectrodesELECTROANALYSIS, Issue 12 2009Xiaohang Zhang Abstract Mineral oil microdroplets containing the model antioxidant N,N -didodecyl- N,,N, -diethyl-phenylene-diamine (DDPD) are immobilized into a 100×100 pore-array (ca. 10,,m individual pore diameter, 100,,m pitch) in a boron-doped diamond electrode surface. The robust diamond surface allows pore filling, cleaning, and reuse without damage to the electrode surface. The electrode is immersed into aqueous electrolyte media, and voltammetric responses for the oxidation of DDPD are obtained. In order to further improve the current responses, 20,wt% of carbon nanofibers are co-deposited with the oil into the pore array. Voltammetric signals are consistent with the oxidation of DDPD and the associated transfer of perchlorate anions (in aqueous 0.1,M NaClO4) or the transfer of protons (in aqueous 0.1,M HClO4). From the magnitude of the current response, the DDPD content in the mineral oil can be determined down to less than 1,wt% levels. Perhaps surprisingly, the reversible (or midpoint) potential for the DDPD oxidation in mineral oil (when immersed in 0.1 NaClO4) is shown to be concentration-dependent and to shift to more positive potential values for more dilute DDPD in mineral oil solutions. An extraction mechanism and the formation of a separate organic product phase are proposed to explain this behavior. [source] Inhibitory effects of N -acetylcysteine on scavenger receptor class A expression in human macrophagesJOURNAL OF INTERNAL MEDICINE, Issue 5 2002L. SVENSSON Abstract.,Svensson L, Norén K, Wiklund O, Lindmark H, Ohlsson B, Mattsson Hultén L (Wallenberg Laboratory for Cardiovascular Research, The Sahlgrenska Academy at Göteborg University, Göteborg; and AstraZeneca, Mölndal, Sweden). Inhibitory effects of N -acetylcysteine on scavenger receptor class A expression in human macrophages. J Intern Med 2002; 251:. Objective.,The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N -acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages. Design.,Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endartherectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL). Results.,Incubation of monocytes and monocyte-derived macrophages with N -acetylcysteine decreased both SR-A I and II mRNA expression. N -Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N -acetylcysteine. After longer periods of incubation with N -acetylcysteine we observed an increased degradation of lipoproteins. Conclusions.,Our results imply that N -acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug. [source] Differential Activation of ERK 1/2 and JNK in Normal Human Fibroblast-like Cells in Response to UVC Radiation Under Different Oxygen Tensions ,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2000Naoki Matsuda ABSTRACT The mechanisms by which mitogen-activated protein kinases (MAPK) respond to the input of UV-induced signal transduction pathways and the resulting biological functions are not well understood. We investigated whether the level of oxygen tension of culture was responsible for the differential activation of MAPK and different cellular outcomes in UVC-irradiated cells. The intracellular oxidative level of normal human fibroblast-like cells in a normal atmosphere (normoxic, 20% O2) was increased within 30 min after UVC irradiation. When cells were cultured at lower oxygen tension in the presence of an antioxidant N -acetyl- l -cysteine (NAC) or under physiologically hypoxic (5% O2) conditions, the elevation of the oxidative level by UV-irradiation was significantly reduced. Among MAPK, extracellular-signal related kinase (ERK) 1/2 was activated by UV regardless of the oxidative level, while c-Jun N-terminal kinase (JNK) activation was inhibited in NAC-treated and in hypoxic cultures. In addition, in cultures at lower oxygen tension, there was less apoptosis and cell survival was enhanced. These results suggest that UV-induced oxidative stress was responsible for intracellular signaling through the JNK pathway. Furthermore, the balance between ERK1/2 and JNK activities after UV irradiation under different oxygen tensions possibly modified cellular outcome in response to UV. [source] Ability of N -acetylcarnosine to protect lens crystallins from oxidation and oxidative damage by radical probe mass spectrometry (RP-MS)RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2010Ji-won Ha The application of Radical Probe Mass Spectrometry based on protein footprinting studies is described to investigate the effectiveness of the antioxidant N -acetylcarnosine (NAC) in preventing oxidative damage to lens crystallins present in the eye of mammals. Despite separate clinical trials which have reported the benefit of administering NAC to the eye as a 1% topical solution for the treatment of human cataract, no evidence was found to suggest that the antioxidant had any significant direct effect on reducing the levels of oxidation within the most abundant lens crystallins, , and ,-crystallin, at the molecular level at increasing concentrations of NAC. The results of this laboratory study suggest that the therapeutic benefit demonstrated in clinical trials is associated with the nature or formulation of the topical solution and/or that the mode of action of NAC as an antioxidant is not a direct one. Copyright © 2010 John Wiley & Sons, Ltd. [source] N -acetylcysteine augments adenovirus-mediated gene expression in human endothelial cells by enhancing transgene transcription and virus entryTHE JOURNAL OF GENE MEDICINE, Issue 1 2002L. Jornot Abstract Background It has previously been shown that oxidants reduce the efficiency of adenoviral transduction in human umbilical vein endothelial cells (HUVECs). In this study, the effect of the antioxidant N -acetylcysteine (NAC) in adenovirus-mediated gene transfer has been investigated. Methods HUVECs were pretreated or not with NAC, and infected with E1E3-deleted adenovirus (Ad) containing the LacZ gene expressed from the RSV-LTR promoter/enhancer in the presence and absence of NAC. Transgene expression was assessed at the protein level (histochemical staining, measurement of ,-Gal activity, and western blot), mRNA level (real-time RT-PCR) and gene level (nuclear run on) 24,h and 48,h after infection. Adenoviral DNA was quantitated by real-time PCR, and cell surface expression of Coxsackie/adenovirus receptors (CAR) was determined by FACS analysis. Results Pretreatment of cells with NAC prior to Ad infection enhanced ,-Gal activity by two-fold due to an increase in viral DNA, which was related to increased CAR expression. When NAC was present only during the post-infection period, a five-fold increase in ,-Gal activity and LacZ gene transcriptional activity was observed. When NAC was present during both the pretreatment and the post-infection period, ,-Gal activity was further enhanced, by 15-fold. Augmentation of ,-Gal activity was paralleled by an increase in ,-Gal protein and mRNA levels. NAC did not affect the half-life of LacZ mRNA. Conclusion Pretreatment with NAC prior to Ad infection enhances virus entry, while treatment with NAC post-infection increases transgene transcription. This strategy permits the use of lower adenoviral loads and thus might be helpful for gene therapy of vascular diseases. Copyright © 2001 John Wiley & Sons, Ltd. [source] Inhibitory effects of N -acetylcysteine on the functional responses of human eosinophils in vitroCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2007M. Martinez-Losa Summary Background Oxidative stress appears to be relevant in the pathogenesis of inflammation in allergic diseases like bronchial asthma. Eosinophils are oxidant-sensitive cells considered as key effectors in allergic inflammation. Objective The aim of this work was to study the effects of the clinically used antioxidant N -acetyl- l -cysteine (NAC) on the functional responses of human-isolated eosinophils. Methods Human eosinophils were purified from the blood of healthy donors by a magnetic bead separation system. The effects of NAC were investigated on the generation of reactive oxygen species (chemiluminescence and flow cytometry), Ca2+ signal (fluorimetry), intracellular glutathione (GSH; flow cytometry), p47phox,p67phox translocation (Western blot) and eosinophil cationic protein (ECP) release (radioimmunoassay). Results NAC (0.1,1 mm) inhibited the extracellular generation of oxygen species induced by N -formyl- l -methionyl- l -leucyl- l -phenylalanine (fMLP) and eotaxin (in the presence of IL-5) with ,logIC50 values of 3.61±0.03 and 3.36±0.09, respectively. Also, the intracellular generation of hydrogen peroxide was virtually abolished by NAC (0.5,1 mm). NAC (1 mm) did not alter the fMLP-induced Ca2+ signal but augmented the eosinophil content of reduced GSH and inhibited p47phox,p67phox translocation. NAC inhibited the release of ECP (,90% inhibition at 1 mm) from fMLP-activated eosinophils. Conclusion Inhibition by NAC of human eosinophil functions in vitro is potentially useful in the treatment of allergic inflammation. [source] Characterization of Cd-induced molecular events prior to cellular damage in primary rat hepatocytes in culture: Activation of the stress activated signal protein JNK and transcription factor AP-1JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2004Chin-ju J. Hsiao Abstract The effect of Cadmium (Cd) on the expression of c-Jun N -terminal kinase (JNK), c-jun, and activator protein-1 (AP-1) has been investigated. We previously reported that Cd causes cell damage as indicated by increases in the cytotoxic parameters, lactate dehydrogenase and lipid peroxidation, and this damage was mediated by decreases in cellular concentration of glutathione. In the present study, we investigate the molecular events involved prior to the Cd-induced cellular toxicity and damage in primary rat hepatocytes. We propose that Cd, through the generation of reactive oxygen species (ROS) and prior to significant cellular damage, activates the stress activated signal protein JNK, regulates c-jun expression, and promotes the binding of a redox sensitive transcription factor AP-1. We show JNK activity and c-jun mRNA level significantly increased at 1 h and AP-1 DNA binding activity significantly enhanced at 3 h in the presence of 4 ,M cadmium chloride. Blocking the Cd induction of JNK activity, c-jun mRNA level, and AP-1 binding activity using the antioxidants N -acetyl cysteine (10 mM) or carnosol (0.5 ,g/mL) suggests a role for ROS. Blocking JNK activity and c-jun mRNA by SP600125 (20 ,M), a JNK inhibitor, supports the role of JNK in transmission of signals induced by Cd. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:133,142, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20018 [source] Curcumin-induced fibroblast apoptosis and in vitro wound contraction are regulated by antioxidants and heme oxygenase: implications for scar formationJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2009A. Scharstuhl Abstract Fibroblast apoptosis plays a crucial role in normal and pathological scar formation and therefore we studied whether the putative apoptosis-inducing factor curcumin affects fibroblast apoptosis and may function as a novel therapeutic. We show that 25-,M curcumin causes fibroblast apoptosis and that this could be inhibited by co-administration of antioxidants N -acetyl- l -cysteine (NAC), biliverdin or bilirubin, suggesting that reactive oxygen species (ROS) are involved. This is supported by our observation that 25-,M curcumin caused the generation of ROS, which could be completely blocked by addition of NAC or bilirubin. Since biliverdin and bilirubin are downstream products of heme degradation by heme oxygenase (HO), it has been suggested that HO-activity protects against curcumin-induced apoptosis. Interestingly, exposure to curcumin maximally induced HO-1 protein and HO-activity at 10,15 ,M, whereas, at a concentration of >20-,M curcumin HO-1-expression and HO-activity was negligible. NAC-mediated inhibition of 25-,M curcumin-induced apoptosis was demonstrated to act in part via restored HO-1-induction, since the rescuing effect of NAC could be reduced by inhibiting HO-activity. Moreover pre-induction of HO-1 using 5-,M curcumin protected fibroblasts against 25-,M curcumin-induced apoptosis. On a functional level, fibroblast-mediated collagen gel contraction, an in vitro wound contraction model, was completely prevented by 25-,M curcumin, while this could be reversed by co-incubation with NAC, an effect that was also partially HO-mediated. In conclusion, curcumin treatment in high doses (>25 ,M) may provide a novel way to modulate pathological scar formation through the induction of fibroblast apoptosis, while antioxidants, HO-activity and its effector molecules act as a possible fine-tuning regulator. [source] Decreased oxidative stress and greater bone anabolism in the aged, when compared to the young, murine skeleton with parathyroid hormone administrationAGING CELL, Issue 5 2010Robert L. Jilka Summary Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. Parathyroid hormone produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26- when compared to 6 -month-old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae, and the toughness of both vertebrae and femora in old, but not young, mice. Parathyroid hormone also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species, p66Shc phosphorylation, and expression of the lipoxygenase Alox15, and it increased glutathione and stimulated Wnt signaling in bone of old mice. Parathyroid hormone also antagonized the effects of oxidative stress on p66Shc phosphorylation, Forkhead Box O transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N -acetyl cysteine or pegylated catalase reduced osteoblast progenitors and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation, it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling. [source] Antipsoriatic drug anthralin induces EGF receptor phosphorylation in keratinocytes: requirement for H2O2 generationEXPERIMENTAL DERMATOLOGY, Issue 2 2004Dominik Peus Abstract: Even though anthralin is a well-established topical therapeutic agent for psoriasis, little is known about its effects and biochemical mechanisms of signal transduction. In contrast to a previous report, we found that anthralin induced time- and concentration-dependent phosphorylation of epidermal growth factor receptor in primary human keratinocytes. Four lines of evidence show that this process is mediated by reactive oxygen species. First, we found that anthralin induces time-dependent generation of H2O2. Second, there is a correlation between a time-dependent increase in anthralin-induced epidermal growth factor receptor phosphorylation and H2O2 generation. Third, the structurally different antioxidants n -propyl gallate and N -acetylcysteine inhibited epidermal growth factor receptor phosphorylation induced by anthralin. Fourth, overexpression of catalase inhibited this process. The epidermal growth factor receptor-specific tyrosine kinase inhibitor PD153035 abrogated anthralin-induced epidermal growth factor receptor phosphorylation and activation of extracellular-regulated kinase 1/2. These findings establish the following sequence of events: (1) H2O2 generation, (2) epidermal growth factor receptor phosphorylation, and (3) extracellular-regulated kinase activation. Our data identify anthralin-induced reactive oxygen species and, more specifically, H2O2 as an important upstream mediator required for ligand-independent epidermal growth factor receptor phosphorylation and downstream signaling. [source] | ||||||||||||||||