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Antioxidant Mechanism (antioxidant + mechanism)
Selected AbstractsMice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamineEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2001Åsa Petersén Abstract Huntington's disease is an autosomal dominant hereditary neurodegenerative disorder characterized by severe striatal cell loss. Dopamine (DA) has been suggested to play a role in the pathogenesis of the disease. We have previously reported that transgenic mice expressing exon 1 of the human Huntington gene (R6 lines) are resistant to quinolinic acid-induced striatal toxicity. In this study we show that with increasing age, R6/1 and R6/2 mice develop partial resistance to DA- and 6-hydroxydopamine-mediated toxicity in the striatum. Using electron microscopy, we found that the resistance is localized to the cell bodies and not to the neuropil. The reduction of dopamine and cAMP regulated phosphoprotein of a molecular weight of 32 kDa (DARPP-32) in R6/2 mice does not provide the resistance, as DA-induced striatal lesions are not reduced in size in DARPP-32 knockout mice. Neither DA receptor antagonists nor a N -methyl- d -aspartate (NMDA) receptor blocker reduce the size of DA-induced striatal lesions, suggesting that DA toxicity is not dependent upon DA- or NMDA receptor-mediated pathways. Moreover, superoxide dismutase-1 overexpression, monoamine oxidase inhibition and the treatment with the free radical scavenging spin-trap agent phenyl-butyl-tert-nitrone (PBN) also did not block DA toxicity. Levels of the antioxidant molecules, glutathione and ascorbate were not increased in R6/1 mice. Because damage to striatal neurons following intrastriatal injection of 6-hydroxydopamine was also reduced in R6 mice, a yet-to-be identified antioxidant mechanism may provide neuroprotection in these animals. We conclude that striatal neurons of R6 mice develop resistance to DA-induced toxicity with age. [source] Influence of subacute treatment of some plant growth regulators on serum marker enzymes and erythrocyte and tissue antioxidant defense and lipid peroxidation in ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2006Ismail Celik Abstract This study aims to investigate the effects of the plant growth regulators (PGRs) (2,3,5-triiodobenzoic acid (TIBA), Naphthaleneacetic acid (NAA), and 2,4-dichlorofenoxyacetic acid (2,4-D)) on serum marker enzymes (aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH)), antioxidant defense systems (reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT)), and lipid peroxidation content (malondialdehyde = MDA) in various tissues of rats. 50 and 100 ppm of PGRs as drinking water were administered orally to rats (Sprague,Dawley albino) ad libitum for 25 days continuously. The PGRs treatment caused different effects on the serum marker enzymes, antioxidant defense systems, and the MDA content in experimented rats compared to controls. Results showed that TIBA caused a significant decrease in serum AST activity with both the dosage whereas serum CPK was significantly increased with 100 ppm dosage of TIBA. Meanwhile, serum AST, CPK, and LDH activities were significantly increased with both dosage of NAA and 2,4-D. The lipid peroxidation end-product MDA significantly increased in the all tissues treated with both dosages of PGRs without any change in the brain and erythrocyte of rats treated with both the dosages of 2,4-D. The GSH depletion in the kidney and brain tissues of rats treated with both dosages of PGRs was found to be significant. Furthermore, the GSH depletion in the erythrocyte of rats treated with both dosages of PGRs except 50 ppm dosage of 2,4-D was significant too. Also, the GSH level in the liver was significantly depleted with 50 ppm of 2,4-D and NAA, whereas the GSH depletion in the same tissue did not significantly change with the treatment. The activity of antioxidant enzymes was also seriously affected by PGRs; SOD significantly decreased in the liver, heart, kidney, and brain of rats treated with both dosages of NAA, whereas the SOD activity in the erythrocytes, liver, and heart was either significantly decreased or not changed with two doses of 2,4-D and TIBA. Although the CAT activity significantly increased in the erythrocyte and brain of rats treated with both doses of PGRs, it was not changed in the liver, heart, and kidney. Meanwhile, the ancillary enzyme GR activity significantly increased in the brain, heart, and liver but decreased in the erythrocyte and kidney of rats treated with both doses of PGRs. The drug-metabolizing enzyme GST activity significantly increased in the heart and kidney but decreased in the brain and erythrocytes of rats treated with both dosages of PGRs. As a conclusion, the results indicate that PGRs might affect antioxidant potential enzymes, the activity of hepatic damage enzymes, and lipid peroxidation dose independently. Also, the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. These data, along with the determined changes, suggest that PGRs produced substantial systemic organ toxicity in the erythrocyte, liver, brain, heart, and kidney during the period of a 25-day subacute exposure. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:174,182, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20134 [source] Melatonin ameliorates hippocampal nitric oxide production and large conductance calcium-activated potassium channel activity in chronic intermittent hypoxiaJOURNAL OF PINEAL RESEARCH, Issue 3 2008Y. W. Tjong Abstract:, Melatonin protects against hippocampal injury induced by intermittent hypoxia (IH). IH-induced oxidative stress is associated with decreases in constitutive production of nitric oxide (NO) and in the activity of large conductance calcium-activated potassium (BK) channels in hippocampal neurons. We tested the hypothesis that administration of melatonin alleviates the NO deficit and impaired BK channel activity in the hippocampus of IH rats. Sprague,Dawley rats were injected with melatonin (10 mg/kg, i.p.) or vehicle before daily IH exposure for 8 hr for 7 days. The NO and intracellular calcium ([Ca2+]i) levels in the CA1 region of hippocampal slices were measured by electrochemical microsenor and spectrofluorometry, respectively. The activity of BK channels was recorded by patch-clamping electrophysiology in dissociated CA1 neurons. Malondialdehyde levels were increased in the hippocampus of hypoxic rats and were lowered by the melatonin treatment. Levels of NO under resting and hypoxic conditions, and the protein expression of neuronal NO synthase (nNOS) were significantly reduced in the CA1 neurons of hypoxic animals compared with the normoxic controls. These deficits were mitigated in the melatonin-treated hypoxic rats with an improved [Ca2+]i response to acute hypoxia. The open probability of BK channels was decreased in the hypoxic rats and was partially restored in the melatonin-treated animals, without alterations in the expression of channel subunits and unitary conductance. Acute treatment of melatonin had no significant effects on the BK channel activity or on the [Ca2+]i response to hypoxia. Collectively, these results suggest that melatonin ameliorates the constitutive NO production and BK channel activity via an antioxidant mechanism against an IH-induced down-regulation of nNOS expression in hippocampal neurons. [source] Theoretical Prediction of the Phenoxyl Radical Formation Capacity and Cyclooxygenase Inhibition Relationships by Phenolic CompoundsMOLECULAR INFORMATICS, Issue 6 2002Juan Ruiz Abstract Due to the importance of the O-H bond dissociation in the antioxidant mechanism of anti-inflammatory phenols, we studied the biradical process Ph-OH,PhO.+H. for 25 phenolic compounds using ab initio calculations. Enthalpies of reaction (,Hr), changes in the electron density at the O-H bond critical point (,OH) and total atomic charges of ortho and para carbon atoms strongly correlate with the in vitro inhibition of cyclooxygenase activity by phenols. The most active compounds have large values of the electron density at the O-H bond (,OH), thus favouring the O-H bond dissociation. In contrast, inactive compounds have small values of the electron density at the O-H bond (,OH), thus reducing the hydrogen donation ability. These results are also supported by the representation of the molecular electrostatic potentials maps. The prediction of the cyclooxygenase inhibitory activity of the proposed QSAR equations is analysed using the multilineal (MLR) method. Finally, the differences in biological activity are examined by analysing the binding interactions of active compounds in the pocket site of human COX-2 enzyme structure derived from crystallographic X -ray data. [source] Overproduction of reactive oxygen species in end-stage renal disease patients: A potential component of hemodialysis-associated inflammationHEMODIALYSIS INTERNATIONAL, Issue 1 2005Marion Morena Abstract During the past decade, hemodialysis (HD)-induced inflammation has been linked to the development of long-term morbidity in end-stage renal disease (ESRD) patients on regular renal replacement therapy. Because interleukins and anaphylatoxins produced during HD sessions are potent activators for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an example of an enzyme that is responsible for overproduction of reactive oxygen species (ROS), this may constitute a link between leukocyte activation and cell or organ toxicity. Oxidative stress, which results from an imbalance between oxidant production and antioxidant defense mechanisms, has been documented in ESRD patients using lipid and/or protein oxidative markers. Characterization of HD-induced oxidative stress has included identification of potential activators for NADPH oxidase. Uremia per se could prime phagocyte oxidative burst. HD, far from improving the oxidative status, results in an enhancement of ROS owing to hemoincompatibility of the dialysis system, hemoreactivity of the membrane, and trace amounts of endotoxins in the dialysate. In addition, the HD process is associated with an impairment in antioxidant mechanisms. The resulting oxidative stress has been implicated in long-term complications including anemia, amyloidosis, accelerated atherosclerosis, and malnutrition. Prevention of oxidative stress in HD might focus on improving the hemocompatibility of the dialysis system, supplementation of deficient patients with antioxidants, and modulation of NADPH oxidase by pharmacologic approaches. [source] Effects of a Brazilian herbal compound as a cosmetic eyecare for periorbital hyperchromia ("dark circles")JOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2009Samara Eberlin PhD Summary Background, Evidence suggests that periorbital hyperchromia (dark circles) occurs mainly as a consequence of postinflammatory hemodynamic congestion producing a typical bruising aspect on the lower eyelids. Aims, To evaluate the clinical effects of Pfaffia paniculata/Ptychopetalum olacoides B./Lilium candidum L.-associated compound (PPLAC) on periorbital hyperchromia and to study in vitro its underlying anti-inflammatory and antioxidant mechanisms. Methods, Twenty-one volunteers presenting with periorbital hyperchromia received a serum sample containing 5.0% PPLAC, which was applied topically in the periorbital area twice a day for 28 days. Skin color was measured using variations in the individual typological angle (,ITA0) and skin luminance (,L*) calculated in the area around the eyes and in the adjacent area. Colorimetric readings were taken at the onset and end of the 28-day treatment. Volunteers were also asked to fill out a questionnaire concerning the improvement in "dark circles." The anti-inflammatory and antioxidant effects of PPLAC were measured by quantification of prostaglandin E2, leukotriene B4, histamine, and superoxide dismutase levels using an in vitro model of human skin culture. Results, Topical application of PPLAC led to a significant improvement in skin luminance and tone in the periorbital area, which was demonstrated by increased values of ITA0 and L* in about 90% of volunteers. In addition, subjects reported reduced intensity and improved appearance of "dark circles." A dose-dependent decreased production of inflammatory mediators, concomitant to increased antioxidant enzyme levels, was observed in our in vitro studies, under basal and lipopolysaccharide-stimulated conditions. Conclusions, Although the precise mechanisms related to PPLAC remain to be clarified, our results indicate that the reduction in the inflammatory process as well as the antioxidant protection against deleterious elements may be considered as an integral approach to preserve the integrity of vascular endothelium, preventing the hemodynamic congestion that culminates in the formation of "dark circles" around the eyes. [source] Salivary free radical-scavenging activity is affected by physical and mental activitiesORAL DISEASES, Issue 6 2008T Atsumi Objective and design:, Free radicals/reactive oxygen species (ROS) are related to inflammation, aging, and cancer. However, living systems have essential antioxidant mechanisms by which these harmful radicals can be scavenged, i.e., free radical-scavenging activity (FRSA). We measured the circadian rhythm of such activities by detecting salivary FRSA in healthy adults, and also examined how salivary FRSA is affected by physical and mental activities, which included (1) ingestion of beverage, (2) exercise, (3) comfortable/uncomfortable stimulation, and (4) smoking. Methods:, FRSA was determined by using the DPPH (1,1,-diphenyl-2-picrylhydrazyl) method. Statistical analysis for experimentally obtained median values was carried out using the Wilcoxon signed rank test. Results:, In circadian rhythm, FRSA was increased by food ingestion and relaxation. As to the individual activities, green tea and coffee ingestion increased FRSA, whereas swimming (P < 0.05) and dance lessons (P < 0.01) decreased it. Watching an amusing video program (P < 0.001) or stimulation by a pleasant aroma (P < 0.01) increased FRSA. In contrast, an unpleasant odor had no effect on FRSA. FRSA decreased immediately after smoking (P < 0.05), but increased thereafter (P < 0.01). Conclusion:, Salivary FRSA was affected not only by physical activities, but also by mental activities. It may be a parameter for reflecting the health status of individuals. [source] Hydroxycinnamic Acids as DNA-Cleaving Agents in the Presence of CuII Ions: Mechanism, Structure,Activity Relationship, and Biological ImplicationsCHEMISTRY - A EUROPEAN JOURNAL, Issue 46 2009Gui-Juan Fan Abstract The effectiveness of hydroxycinnamic acids (HCAs), that is, caffeic acid (CaA), chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA), 3-hydroxycinnamic acid (3-HCA), and 4-hydroxycinnamic acid (4-HCA), as pBR322 plasmid DNA-cleaving agents in the presence of CuII ions was investigated. Compounds bearing o -hydroxy or 3,5-dimethoxy groups on phenolic rings (CaA, SA, and ChA) were remarkably more effective at causing DNA damage than the compounds bearing no such groups; furthermore, CaA was the most active among the HCAs examined. The involvement of reactive oxygen species (ROS) and CuI ions in the DNA damage was affirmed by the inhibition of the DNA breakage by using specific scavengers of ROS and a CuI chelator. The interaction between CaA and CuII ions and the influence of ethylenediaminetetraacetic acid (EDTA), the solvent, and pH value on the interaction were also studied to help elucidate the detailed prooxidant mechanism by using UV/Vis spectroscopic analysis. On the basis of these observations, it is proposed that it is the CaA phenolate anion, instead of the parent molecule, that chelates with the CuII ion as a bidentate ligand, hence facilitating the intramolecular electron transfer to form the corresponding CaA semiquinone radical intermediate. The latter undergoes a second electron transfer with oxygen to form the corresponding o -quinone and a superoxide, which play a pivotal role in the DNA damage. The intermediacy of the semiquinone radical was supported by isolation of its dimer from the CuII -mediated oxidation products. Intriguingly, CaA was also the most cytotoxic compound among the HCAs toward human promyelocytic leukemia (HL-60) cell proliferation. Addition of exogenous CuII ions resulted in an effect dichotomy on cell viability depending on the concentration of CaA; that is, low concentrations of CaA enhanced the cell viability and, conversely, high concentrations of CaA almost completely inhibited the cell proliferation. On the other hand, when superoxide dismutase was added before, the two stimulation effects of exogenous CuII ions were significantly ameliorated, thus clearly indicating that the oxidative-stress level regulates cell proliferation and death. These findings provide direct evidence for the antioxidant/prooxidant mechanism of cancer chemoprevention. [source] | ||||||||||||||||