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Free Radical Production (free + radical_production)
Selected AbstractsAlcohol-induced free radicals in mice: Direct toxicants or signaling molecules?HEPATOLOGY, Issue 5 2001Ming Yin Tumor necrosis factor , (TNF-,) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor , receptor 1 (TNF-R1) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-, production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-, production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-R1 knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57Bl/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-R1; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-, production and do not directly damage cells in early alcohol-induced hepatic injury. [source] In vitro antioxidant activities of mouthrinses and their componentsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2002M. Battino Abstract Objectives: Several forms of periodontal diseases (PD) are often associated with activated phagocytosing leukocytes and contemporary free radical production. Host antioxidant defenses could benefit from mouthrinses used as adjuncts to counteract plaque-associated bacteria. The aim of the present study was to determine possible antioxidant activity (AA) of a number of antiseptic mouthrinses and of their stated active principles (AP), regardless of their efficacy as antimicrobial agents. Material and Methods: The antioxidant activities of 11 mouthrinses and their active principles were tested with a specific spectrophotometric method. Comet assay was used to test whether pure chemical antioxidant activity actually corresponded to prevention of in vitro DNA fragmentation. Results: Methylsalicylate-containing mouthrinses were the most effective. Several compounds, and some vehicles, behaved as antioxidants. Fibroblast DNA fragmentation was limited by preincubation with methylsalicylate-containing mouthrinse but was unaffected by treatment with chlorexidine. Conclusion: The results described herein indicate that several mouthrinses possess AA; such a property could be ascribed to either AP or vehicles or both. All the data were obtained in systems in vitro and the demonstration of in vivo AA is necessary. These findings could be useful in the treatment of some forms of PD and should be considered when arranging new mouthrinse formulations. Zusammenfassung In vitro antioxidative Aktivitäten von Mundwässern und ihren Komponenten Ziele:,Verschiedene Formen von parodontalen Erkrankungen (PD) sind häufig mit aktivierten phagozytierenden Leukozyten und gleichzeitiger Produktion von freien Radikalen verbunden. Die Antioxydantienabwehr des Wirtes könnte von Mundwässern genützt werden, die als Adjunktive zur Bekämpfung der plaque-assoziierten Bakterien verwendet werden. Das Ziel der vorliegenden Studie war die Bestimmung der möglichen Antioxydantienaktivität (AA) von einer Anzahl antiseptischer Mundwässer und ihrer angegebenen aktiven Prinzipien (AP), unabhängig von ihrer Effektivität als antimikrobielle Agentien. Material und Methoden:,Die antioxydative Aktivität von 11 Mundwässern und ihre Aktivitätsprinzipien wurden mit einer spezifischen Spektralphotometrie getestet. Ein Assay wurde für die Testung genutzt, ob die reine chemische antioxydative Aktivität tatsächlich mit der Prävention der in vitro DNA Fragmentation korrespondiert. Ergebnisse:,Methylsalicylat enthaltende Mundwässer waren am effektivsten. Verschiedene Bestandteile und einige Vehikel verhielten sich wie Antioxydantien. Fibroblasten DNA Fragmentation wurde durch Präinkubation mit Methylsalicylat enthaltende Mundwässer begrenzt, war aber unbeeinflusst durch Behandlung mit Chlorhexidin. Schlussfolgerung:,Die beschriebenen Ergebnisse zeigen, dass verschiedene Mundwässer über AA verfügen; solch eine Eigenschaft könnte entweder AP oder Vehikeln oder beiden zugeschrieben werden. Alle Daten sind in in vitro Systemen gewonnen worden, aber die Demonstration der in vivo AA ist notwendig. Diese Ergebnisse könnten in der Behandlung von einigen Formen der PD nützlich sein und sollten bei der Entwicklung neuer Mundwasserrezepte beachtet werden. Résumé Activité antioxydante in vitro des bains de bouche et de leurs composants Buts:,Plusieurs formes d'affections parodontales (periodontal diseases, PD) sont souvent associées à des leucocytes phagocytaires activés et à la production de radicaux libres contemporains. L'utilisation de bains de bouche comme adjuvants pourrait être bénéfique aux défenses antioxidantes de l'hôte pour lutter contre les bactéries de plaque. L'objectif de cette étude était de déterminer l'activité antioxydante (antioxidant activity, AA) potentielle d'un certain nombre de bains de bouche antiseptiques et de leurs principes actifs reconnus (active principles, AP), indifféremment de leur efficacité en tant qu'agents antimicrobiens. Matériaux et méthodes:,L'activité antioxydante de 11 bains de bouche et de leurs principes actifs a été testée à l'aide d'une méthode spectrophotométrique spécifique. Le test Comet a été utilisé pour voir si l'activité antioxydante chimique pure permet effectivement de prévenir la fragmentation de l'ADN in vitro. Résultats:,Les bains de bouche contenant du méthylsalicylate étaient les plus efficaces. Plusieurs composés et certains vecteurs se comportaient comme des antioxydants. La pré-incubation dans des bains de bouche contenant du méthylsalicylate limitait la fragmentation de l'ADN des fibroblastes, mais le traitement à la chlorhexidine ne l'affectait pas. Conclusion:,Les résultats décrits dans cette étude indiquent que plusieurs bains de bouche possèdent une AA, propriété qui pourrait être attribuée aux AP ou aux véhicules ou aux deux. Toutes les données ont été obtenues sur des systèmes in vitro, et l'AA in vivo reste à démontrer. Ces résultats pourraient s'avérer utiles pour le traitement de certaines formes de PD et devraient être pris en compte lors de l'élaboration de nouvelles formulations de bains de bouche. [source] Morphine and HIV-Tat increase microglial-free radical production and oxidative stress: possible role in cytokine regulationJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Jadwiga Turchan-Cholewo Abstract Opiate abuse alters the progression of human immunodeficiency virus and may increase the risk of neuroAIDS. As neuroAIDS is associated with altered microglial reactivity, the combined effects of human immunodeficiency virus-Tat and morphine were determined in cultured microglia. Specifically, experiments determined the effects of Tat and morphine on microglial-free radical production and oxidative stress, and on cytokine release. Data show that combined Tat and morphine cause early and synergistic increases in reactive oxygen species, with concomitant increases in protein oxidation. Furthermore, combined Tat and morphine, but not Tat or morphine alone, cause reversible decreases in proteasome activity. The effects of morphine on free radical production and oxidative stress are prevented by pre-treatment with naloxone, illustrating the important role of opioid receptor activation in these phenomena. While Tat is well known to induce cytokine release from cultured microglia, morphine decreases Tat-induced release of the cytokines tumor necrosis factor-, and interleukin-6, as well as the chemokine monocyte chemoattractant protein-1 (MCP-1). Finally, experiments using the reversible proteasome inhibitor MG115 show that temporary, non-cytotoxic decreases in proteasome activity increase protein oxidation and decrease tumor necrosis factor-,, interleukin-6, and MCP-1 release from microglia. Taken together, these data suggest that oxidative stress and proteasome inhibition may be involved in the immunomodulatory properties of opioid receptor activation in microglia. [source] NO-induced neuroprotection in ischemic preconditioning stimulates mitochondrial Mn-SOD activity and expression via RAS/ERK1/2 pathwayJOURNAL OF NEUROCHEMISTRY, Issue 4 2007A. Scorziello Abstract To identify the transductional mechanisms responsible for the neuroprotective effect of nitric oxide (NO) during ischemic preconditioning (IPC), we investigated the effects of this gaseous mediator on mitochondrial Mn-superoxide dismutase (Mn-SOD) expression and activity. In addition, the possible involvement of Ras/extracellular-regulated kinase (ERK) ERK1/2 pathway in preserving cortical neurons exposed to oxygen and glucose deprivation (OGD) followed by reoxygenation was also examined. Ischemic preconditioning was obtained by exposing neurons to a 30-min sublethal OGD (95% N2 and 5% CO2). Then, after a 24-h interval, neurons were exposed to 3 h of OGD followed by 24 h of reoxygenation (OGD/Rx). Our results revealed that IPC reduced cytochrome c (cyt c) release into the cytosol, improved mitochondrial function, and decreased free radical production. Moreover, it induced an increase in nNOS expression and NO production and promoted ERK1/2 activation. These effects were paralleled by an increase in Mn-SOD expression and activity that persisted throughout the following OGD phase. When the neurons were treated with L-NAME, a well known NOS inhibitor, the increase in Mn-SOD expression occurring during IPC was reduced and, as a result, IPC-induced neuroprotection was prevented. Similarly, when ERK1/2 was inhibited by its selective inhibitor PD98059, the increase in Mn-SOD expression observed during IPC was almost completely abolished. As a result, its neuroprotective effect on cellular survival was thwarted. The present findings indicate that during IPC the increase in Mn-SOD expression and activity are paralleled by NO production. This suggests that NO neuroprotective role occurs through the stimulation of Mn-SOD expression and activity. In particular, NO via Ras activation stimulates downstream ERK1/2 cascade. This pathway, in turn, post-transcriptionally activates Mn-SOD expression and activity, thus promoting neuroprotection during preconditioning. [source] Neurotoxic mechanisms of 2,9-dimethyl-,-carbolinium ion in primary dopaminergic cultureJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Juliane Hamann Abstract ,-Carbolines are potential endogenous and exogenous neurotoxicants that may contribute to the pathogenesis of Parkinson's disease. The 2,9-dimethyl-,-carbolinium ion (either 2,9-dimethyl-,-norharmanium or 2,9-Me2NH+) was found to be neurotoxic in primary mesencephalic cultures and to be a potent inhibitor of mitochondrial complex I. However, the precise mechanisms of cell death remained obscure. Here, we investigated the mechanism of cell death in primary dopaminergic cultures of the mouse mesencephalon mediated by 2,9-Me2NH+. The ,-carboline caused preferential death of dopaminergic neurones, which could not be attributed to cellular uptake via the dopamine transporter. Transient incubation with 2,9-Me2NH+ for 48 h caused a progressive deterioration in the morphology of dopaminergic neurones during a 5-day recovery period and persistent damage to the overall culture. An increase in free radical production and caspase-3 activity, as well as a decrease of respiratory activity, mitochondrial membrane potential and ATP content, contributed to toxicity and pointed to an apoptotic mode of cell death, although a significant quantity of cells dying via necrosis were present simultaneously. These data underline the preferential susceptibility of dopaminergic neurones to 2,9-Me2NH+ as a potent, oxidative stress generating neurotoxin. [source] Vitamin E blocks early events induced by 1-methyl-4-phenylpyridinium (MPP+) in cerebellar granule cellsJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Rosa A. González-Polo Abstract Exposure of cerebellar granule cells (CGCs) to 1-methyl-4-phenylpyridinium (MPP+) results in apoptotic cell death, which is markedly attenuated by co-treatment of CGCs with the radical scavenger vitamin E. Analysis of free radical production and mitochondrial transmembrane potential (,,m), using specific fluorescent probes, showed that MPP+ mediates early radical oxygen species (ROS) production without a loss of ,,m. Exposure to MPP+ also produces an early increase in Bad dephosphorylation and translocation of Bax to the mitochondria. These events are accompanied by cytochrome c release from mitochondria to cytosol, which is followed by caspase 3 activation. Exposure of the neurons to vitamin E maintains Bad phosphorylation and attenuates Bax translocation, inhibiting cytochrome c release and caspase activation. MPP+ -mediated cytochrome c release is also prevented by allopurinol, suggesting the participation of xanthine oxidase in the process. Our results indicate that free radicals play an active role in the MPP+ -induced early events that culminate with cell death. [source] Mitochondrial dysfunction in a neural cell model of spinal muscular atrophyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2009Gyula Acsadi Abstract Mutations of the survival motor neuron (SMN) gene in spinal muscular atrophy (SMA) lead to anterior horn cell death. The cause is unknown, but motor neurons depend substantially on mitochondrial oxidative phosphorylation (OxPhos) for normal function. Therefore, mitochondrial parameters were analyzed in an SMA cell culture model using small interfering RNA (siRNA) transfection that decreased Smn expression in NSC-34 cells to disease levels. Smn siRNA knock-down resulted in 35% and 66% reduced Smn protein levels 48 and 72 hr posttransfection, respectively. ATP levels were reduced by 14% and 26% at 48 and 72 hr posttransfection, respectively, suggesting decreased ATP production or increased energy demand in neural cells. Smn knock-down resulted in increased mitochondrial membrane potential and increased free radical production. Changes in activity of cytochrome c oxidase (CcO), a key OxPhos component, were observed at 72 hr with a 26% increase in oxygen consumption. This suggests a compensatory activation of the aerobic pathway, resulting in increased mitochondrial membrane potentials, a condition known to lead to the observed increase in free radical production. Further testing suggested that changes in ATP at 24 hr precede observable indices of cell injury at 48 hr. We propose that energy paucity and increased mitochondrial free radical production lead to accumulated cell damage and eventual cell death in Smn-depleted neural cells. Mitochondrial dysfunction may therefore be important in SMA pathology and may represent a new therapeutic target. © 2009 Wiley-Liss, Inc. [source] Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenolsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2006Zhi 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] Cimetidine: antioxidant and metal-binding propertiesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2002Zaynab Lambat ABSTRACT Cimetidine is one of the most potent H2 receptor antagonists for inhibiting excessive histamine-induced acid secretion and is currently used worldwide to treat peptic ulcers. In this study, levels of free radicals were assessed and the ability of cimetidine to act as an antioxidant was determined using nitroblue-tetrazolium assay and lipid peroxidation assays. Free radical generation in the brain is promoted by the presence of iron, as occurs in the Fenton reaction. The results show that cimetidine reduces the generation of superoxide anion formed in the nitroblue-tetrazolium assay. In addition, cimetidine (1 mm) is able to reduce the iron-induced rise in lipid peroxidation in rat brain homogenates. Electrochemistry, UV/Vis spectroscopy and HPLC experiments show metal-ligand interactions between cimetidine and transition metals. The results imply that cimetidine provides a neuroprotective effect by binding to iron and copper, thus making them unavailable for free radical production. [source] Melatonin stimulates glutathione peroxidase activity in human chorionJOURNAL OF PINEAL RESEARCH, Issue 4 2001Yuji Okatani In preeclampsia, placental production of lipid peroxides is abnormally increased, while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are decreased. Administration of melatonin, a powerful scavenger of oxygen free radicals, also may protect the placenta from free radical-induced damage by increasing the activity of antioxidant enzymes. To test this hypothesis we administered melatonin to pregnant women before they underwent voluntary interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was administered orally at 12:00 hr, and samples of chorion and maternal blood were obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the melatonin concentration in maternal serum and activities of GSH-Px and SOD and levels of melatonin in chorionic homogenates. Melatonin administration was reflected by markedly increased melatonin concentrations in maternal serum and in chorion, with peak levels achieved 1 hr after melatonin administration (serum, 46.87±10.87 nM/L; chorionic homogenate, 4.36±1.56 pmol/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic homogenates increased significantly (P<0.001), with peak levels occurring at 3 hr (51.68±3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated control subjects). No significant changes in chorionic SOD activity occurred during the 3-hr post-administration period. These results indicate that exogenous melatonin increases GSH-Px activity in the chorion and thereby may protect indirectly against free radical injury. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excessive free radical production, such as intrauterine fetal growth retardation and fetal hypoxia. [source] Melatonin increases activities of glutathione peroxidase and superoxide dismutase in fetal rat brainJOURNAL OF PINEAL RESEARCH, Issue 2 2000Yuji Okatani Melatonin is a powerful scavenger of oxygen free radicals. In humans, melatonin is rapidly transferred from the maternal to the fetal circulation. To investigate whether or not maternal melatonin administration can protect the fetal rat brain from radical-induced damage by increasing the activities of antioxidant enzymes, we administered melatonin to pregnant rats on day 20 of gestation. Melatonin (10 mg/kg) was injected intraperitoneally at daytime (14:00 hr) and, to remove the fetuses, a laparotomy was performed at 1, 2, or 3 hr after its administration. We measured the melatonin concentration in the maternal serum and in fetal brain homogenates and determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in fetal brain homogenates. Melatonin administration markedly increased melatonin concentrations in the maternal serum and fetal brain homogenates, with peak levels achieved 1 hr after melatonin administration (serum: 538.2±160.7 pM/mL; brain homogenates: 13.8±2.8 pM/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in fetal brain homogenates increased significantly (P<0.01). Similarly, SOD activity increased significantly between 1 and 2 hr after melatonin administration (P<0.01). These results indicate that melatonin administration to the mother increases antioxidant enzyme activities in the fetal brain and may thereby provide indirect protection against free radical injury. Thus, melatonin may potentially be useful in the treatment of neurodegenerative conditions that may involve excessive free radical production, such as fetal hypoxia and preeclampsia. [source] Microvascular Display of Xanthine Oxidase and NADPH Oxidase in the Spontaneously Hypertensive RatMICROCIRCULATION, Issue 7 2006FRANK A. DELANO ABSTRACT Objective: Oxygen free radical production in hypertension may be associated with elevated arteriolar tone and organ injury. Previous results suggest an enhanced level of oxygen free radical formation in microvascular endothelium and in circulating neutrophils associated with xanthine oxidase activity in the spontaneously hypertensive rats (SHR) compared with their normotensive controls, the Wistar Kyoto rats (WKY). The aim of this study was to gain more detailed understanding of where oxidative enzymes are located in the microcirculation. Methods: An approach was developed to delineate the cellular distribution of two selected oxidative enzymes, xanthine oxidase and nicotinamide adenine dinucleotide phosphate (NADPH) dependent oxidase (protein 67-kDa fraction). Immunolabeling with peroxidase substrate was utilized, which permits full delineation of the primary antibody in all microvascular structures of the mesentery. Results: Xanthine oxidase is present in the endothelium of all segments of the microcirculation, in mast cells, and in parenchymal cells of the mesentery. NADPH oxidase can be detected in the endothelium, leukocytes, and mast cells and with lower levels in parenchymal cells. The mesentery of WKY and SHR has similar enzyme distributions with enhancements on the arteriolar and venular side of the microcirculation that coincide with the sites of enhanced free radical production recently reported. Immune label measurements under standardized conditions indicate that both enzymes are significantly enhanced in the SHR. Adrenalectomy, which serves to reduce the blood pressure and free radical production of the SHR to normotensive levels, leads to a reduction of NADPH and xanthine oxidase to normotensive levels, while supplementation of adrenalectomized SHR with dexamethasone significantly increases the oxidase expression in several parts of the microcirculation to levels above the WKY rats. Conclusion: The results indicate that enhanced expression of NADPH and xanthine oxidase in the SHR depends on an adrenal pathway that is detectable in the arteriolar and venular network at high and low pressure regions of the circulation. [source] Nanoporous aluminum oxide affects neutrophil behaviourMICROSCOPY RESEARCH AND TECHNIQUE, Issue 5 2004M. Karlsson Abstract This study evaluates neutrophil responses on aluminum oxide membranes. Using an in vitro cell culture system, we have found that the pore size (20 and 200 nm in diameter) of alumina membranes have a significant effect on leukocyte morphology and activation. Specifically, our results show that 20-nm pore-size membranes were more potent in triggering PMN spreading and extending of pseudopodia than 200-nm pore-size membranes. The morphological changes are also associated with cell activation. In fact, adherent neutrophils on 20-nm pore-size membranes elicit much stronger initial oxygen free radical production. Overall, our results point out that membrane pore size significantly affects the extent of cellular responses of adherent neutrophils. Microsc. Res. Tech. 63:259,265, 2004. © 2004 Wiley-Liss, Inc. [source] Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damagePHYTOTHERAPY RESEARCH, Issue 8 2003Alessandra Russo Abstract Bacopa monniera L. (family Scrophulariaceae) (BM) is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of BM and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether this plant extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized ,broblasts. It showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. These results were con,rmed by a signi,cant protective effect on H2O2 , induced cytoxicity and DNA damage in human non-immortalized ,broblasts. The antioxidant capacity of BM may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiin,ammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other bene,cial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, this Ayurvedic drug may be useful in the treatment of human pathologies in which free radical production plays a key role. Copyright © 2003 John Wiley & Sons, Ltd. [source] Systemic plant signal triggers genome instabilityTHE PLANT JOURNAL, Issue 1 2004Jody Filkowski Summary Previously, we have shown that infection of tobacco plants with a viral pathogen triggers local and systemic induction of homologous recombination (HR). Here, we have tested the hypothesis of whether free radicals are potentially involved in the induction of the systemic effect. We report a significant induction of HR in tobacco plants treated with radical-generating agents, UVC or rose Bengal (RB). Importantly, the recombination increase was observed in local (treated) as well as systemic (non-treated) tissue. The systemic increase in recombination implies the existence of a signal that is transmitted to non-treated tissue. Several sets of grafting experiments proved the generation of said signal by both RB and UVC exposure. A statistically significant increase in HR was observed in tissue that received a systemic signal via a grafted leaf. Similar data were obtained from transgenic plants naphthalene degrading salicylate 1-hydroxylase (NahG) unable to accumulate salicylic acid (SA). Interestingly, pre-treatment of plants with the radical-scavenging compound N -acetyl- l -cysteine (NAC) led to a significantly lower recombination increase upon grafting after treatment with UVC and RB. Moreover, leaves taken for grafting from NAC-pre-treated plants exhibited a lower level of oxidized organic compounds. Our data suggest the involvement of free radical production in either generation or maintenance of the recombination signal. We discuss potential mechanisms for generation of the signal and possible adaptive advantages of enhanced genomic flexibility following exposure to DNA-damaging agents. [source] Influence of Different Hemodialysis Membranes on Red Blood Cell Susceptibility to Oxidative StressARTIFICIAL ORGANS, Issue 1 2000Leonardo Lucchi Abstract: Oxidative stress is crucial in red blood cell (RBC) damage induced by activated neutrophils in in vitro experiments. The aim of the study was to evaluate whether the bioincompatibility phenomena occurring during hemodialysis (HD) (where neutrophil activation with increased free radical production is well documented) may have detrimental effects on RBC. We evaluated RBC susceptibility to oxidative stress before and after HD in 15 patients using Cuprophan, cellulose triacetate, and polysulfone membrane. RBC were incubated with t-butyl hydroperoxide as an oxidizing agent both in the presence and in the absence of the catalase inhibitor sodium azide. The level of malonaldehyde (MDA), a product of lipid peroxidation, was measured at 0, 5, 10, 15, and 30 min of incubation. When Cuprophan membrane was used, the MDA production was significantly higher after HD, indicating an increased susceptibility to oxidative stress in comparison to pre-HD. The addition of sodium azide enhanced this phenomenon. Both cellulose triacetate and polysulfone membranes did not significantly influence RBC susceptibility to oxidative stress. Neither the level of RBC reduced glutathione nor the RBC glutathione redox ratio changed significantly during HD with any of the membranes used. The RBC susceptibility to oxidative stress was influenced in different ways according to the dialysis membrane used, being increased only when using the more bioincompatible membrane Cuprophan, where neutrophil activation with increased free radical production is well documented. The alterations found in this study might contribute to the reduced RBC longevity of HD patients where a bioincompatible membrane is used. [source] Oxidative stress: The special case of diabetesBIOFACTORS, Issue 1-2 2003N. F. Wiernsperger Abstract The implication of oxidative stress (OS) in diabetes is a major concern for the development of therapeutics aimed at improving the metabolic and/or vascular dysfunctions of this burdening disease. Ample evidence is available suggesting that OS is present in essentially all tissues and can even be observed in prediabetic states. This raises the question of the origin of OS and suggests that, although hyperglycemia is largely linked with free radical production, its role may mainly be the aggravation of a preexisting state. Indeed other factors are also causally linked to OS, such as hormones and lipids. The main debate is about the pertinence of antioxidant therapy since the large scale clinical trials performed recently have essentially failed to show any significant improvement in metabolic or vascular disturbances of diabetic patients. However this conclusion must be tempered by the fact that they have mainly been using vitamin E +/-C; indeed many arguments suggest that either the choice or the application modalities of these substances may have been inadequate. Potential reasons for the actual failure of antioxidant therapy in diabetes are discussed; the indisputable involvement of OS in this disease still leaves hope for alternative therapeutic approaches. [source] Possible biphasic changes of free radicals in ethylene glycol-induced nephrolithiasis in ratsBJU INTERNATIONAL, Issue 9 2000H.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] The Role of Mitochondria in the Pathogenesis of Neurodegenerative DiseasesBRAIN PATHOLOGY, Issue 3 2000Giovanni Manfredim MD A growing body of evidence indicates that mitochondrial dysfunction may play an important role in the pathogenesis of many neurodegenerative disorders. Because mitochondrial metabolism is not only the principal source of high energy intermediates, but also of free radicals, it has been suggested that inherited or acquired mitochondrial defects could be the cause of neuronal degeneration as a consequence of energy defects and oxidative damage. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities, and also as a consequence of mutations in nuclear genes directly involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin. Defects of oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to primary mitochondrial abnormalities. In these cases, the mitochondrial dysfunction is likely to be an epiphenomenon, which, nevertheless, could be of importance in precipitating a cascade of events leading to cell death. In either case, understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could be important for the development of therapeutic strategies in these disorders. [source] |