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Antioxidant Defenses (antioxidant + defense)
Terms modified by Antioxidant Defenses Selected AbstractsAntioxidant Defenses and DNA Damage Induced by UV-A and UV-B Radiation in the Crab Chasmagnathus granulata (Decapoda, Brachyura),PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Glauce R. Gouveia ABSTRACT The photoprotector role of pigment dispersion in the melanophores of the crab, Chasmagnathus granulata, against DNA and oxidative damages caused by UV-A and UV-B was investigated. Intact and eyestalkaless crabs were used. In eyestalkless crabs, the dorsal epidermis of the cephalothorax (dispersed melanophores) and the epidermis of pereiopods (aggregated melanophores) were analyzed. Intact crabs showed only dispersed melanophores in the two epidermis. Antioxidant enzymes activity and lipoperoxidation content were analyzed after UV-A (2.5 J/cm2) or UV-B (8.6 J/sm2) irradiation. DNA damage was analyzed by single cell electrophoresis (comet) assay, after exposure to UV-B (8.6 J/cm2). UV-A radiation increased the glutatione- S -transferase activity in the pereiopods epidermis of eyestalkless crabs (P < 0.05). UV-B radiation induced DNA damage in the dorsal epidermis of eyestalkless crabs (P < 0.005). In pereiopod epidermis of eyestalkless crabs, there was no significant difference between control and UV-B-exposed crabs. In the pereiopods epidermis of eyestalkless, the control group showed higher scores of DNA damage and ,50% of cellular viability. Because in eyestalkless and irradiated crabs the cellular viability was ,5%, it was not possible to observe nuclei for determination of DNA damage. The findings show that melanophores can play a role in the defense against harmful effects of a momentary exposure to UV radiation. [source] ATP-dependent modulation and autophosphorylation of rapeseed 2-Cys peroxiredoxinFEBS JOURNAL, Issue 7 2008Martin Aran 2-Cys peroxiredoxins (2-Cys Prx) are ubiquitous thiol-containing peroxidases that have been implicated in antioxidant defense and signal transduction. Although their biochemical features have been extensively studied, little is known about the mechanisms that link the redox activity and non-redox processes. Here we report that the concerted action of a nucleoside triphosphate and Mg2+ on rapeseed 2-Cys Prx reversibly impairs the peroxidase activity and promotes the formation of high molecular mass species. Using protein intrinsic fluorescence in the analysis of site-directed mutants, we demonstrate that ATP quenches the emission intensity of Trp179, a residue close to the conserved Cys175. More importantly, we found that ATP facilitates the autophosphorylation of 2-Cys Prx when the protein is successively reduced with thiol-bearing compounds and oxidized with hydroperoxides or quinones. MS analyses reveal that 2-Cys Prx incorporates the phosphoryl group into the Cys175 residue yielding the sulfinic-phosphoryl [Prx-(Cys175)-SO2PO32,] and the sulfonic-phosphoryl [Prx-(Cys175)-SO3PO32,] anhydrides. Hence, the functional coupling between ATP and 2-Cys Prx gives novel insights into not only the removal of reactive oxygen species, but also mechanisms that link the energy status of the cell and the oxidation of cysteine residues. [source] Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile studyHEPATOLOGY RESEARCH, Issue 10 2007Sheikh Abdullah Tasduq Aim:, Biochemical characterization of long-term toxic manifestations of anti-tubercular (anti-TB) drugs , rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) , individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats. Methods:, Animals received anti-TB drugs , alone or in combination , once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+-ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule. Results:, Anti-TB drugs-treated animals showed abnormal rises or falls (>1.5,2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15,90 days. The in vivo results were further supported by in vitro results (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. Results indicated that anti-TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant,antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1-mediated bioactivation mechanism. Conclusion:, Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis. [source] The pentose-phosphate pathway in neuronal survival against nitrosative stressIUBMB LIFE, Issue 1 2010Juan P. Bolaños Abstract Neurons are thought to be particularly vulnerable cells against reactive oxygen and nitrogen species (RONS) damage (nitrosative stress), due in part to their weak antioxidant defense and low ability to compensate energy homeostasis. Intriguingly, nitrosative stress efficiently stimulates the rate of the antioxidant pentose-phosphate pathway (PPP), which generates NADPH a necessary cofactor for the reduction of glutathione disulfide. In fact, inhibition of PPP sensitizes cultured neurons to glutathione oxidation and apoptotic death, whereas its stimulation confers resistance to nitrosative stress. Furthermore, we recently described that neurons can preferentially use glucose through the PPP by inhibiting glycolysis, which is achieved by continuously degrading the glycolytic positive-effector protein, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (Pfkfb3) by the action of the E3 ubiquitine ligase anaphase-promoting complex/cyclosome (APC/C)Cdh1. These results suggest that the antioxidant fragility of neurons may be compensated by the PPP at the expense of inhibiting bioenergetic glycolysis. © 2009 IUBMB IUBMB Life, 62(1):14,18, 2010 [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] Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic ratsJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2001Ruth A. Sanders Abstract In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:143,149, 2001 [source] Effects of ageing on carbonyl stress and antioxidant defense in RBCs of obese Type 2 diabetic patientsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2005Alina Constantin Abstract In this study we investigated the effects of ageing on the carbonyl stress (protein carbonyls and 4-hydroxy-2-nonenal groups) and glutathione antioxidant defense in red blood cells (RBCs) of obese Type 2 diabetic patients with/without hypertensive complications. To this purpose the following methods were used: spectrophotometry (protein carbonyls, glutathione and glutathione peroxidase assays), immunofluorescence (4-hydroxy-2-nonenal localization), western blotting (immunodetection of carbonylated proteins). The results showed that compared to RBCs of healthy subjects, in obese Type 2 diabetics, ageing is associated with: (i) an increase in the concentration and expression of carbonylated proteins, a marker of oxidative stress; (ii) a decrease of both non-enzymatic and enzymatic endogenous glutathione defenses; (iii) a severely disturbed oxidant/antioxidant balance when obesity was associated with hypertension. The simultaneous insults of high blood pressure, obesity, and diabetes conducted to the highest carbonyl strss, exposure of 4-hydroxy-2-nonenal Michel adducts at the outer leaflet of RBCs plasmalemma, and the lowest glutathione antioxidant potential, particularly in elderly patients. These results can explain the gradual age-dependent diminishment of the detoxification potenital of RBCs that at the old age can not overcome the deleterious effects of the high systemic oxidative stress. [source] Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in miceAGING CELL, Issue 1 2010James R. Mitchell Summary Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2,4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals. [source] Redox-based endoplasmic reticulum dysfunction in neurological diseasesJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Gábor Bánhegyi Abstract The redox homeostasis of the endoplasmic reticulum lumen is characteristically different from that of the other subcellular compartments. The concerted action of membrane transport processes and oxidoreductase enzymes maintain the oxidized state of the thiol-disulfide and the reducing state of the pyridine nucleotide redox systems, which are prerequisites for the normal functions of the organelle. The powerful thiol-oxidizing machinery allows oxidative protein folding but continuously challenges the local antioxidant defense. Alterations of the cellular redox environment either in oxidizing or reducing direction affect protein processing and may induce endoplasmic reticulum stress and unfolded protein response. The activated signaling pathways attempt to restore the balance between protein loading and processing and induce apoptosis if the attempt fails. Recent findings strongly support the involvement of this mechanism in brain ischemia, neuronal degenerative diseases and traumatic injury. The redox changes in the endoplasmic reticulum are integral parts of the pathomechanism of neurological diseases, either as causative agents, or as complications. [source] Preferential vulnerability of mesencephalic dopamine neurons to glutamate transporter dysfunctionJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Imane Nafia Abstract Nigral depletion of the main brain antioxidant GSH is the earliest biochemical event involved in Parkinson's disease pathogenesis. Its causes are completely unknown but increasing number of evidence suggests that glutamate transporters [excitatory amino acid transporters (EAATs)] are the main route by which GSH precursors may enter the cell. In this study, we report that dopamine (DA) neurons, which express the excitatory amino acid carrier 1, are preferentially affected by EAAT dysfunction when compared with non-DA neurons. In rat embryonic mesencephalic cultures, l -trans-pyrrolidine-2,4-dicarboxylate, a substrate inhibitor of EAATs, is directly and preferentially toxic for DA neurons by decreasing the availability of GSH precursors and lowering their resistance threshold to glutamate excitotoxicity through NMDA-receptors. In adult rat, acute intranigral injection of l -trans-pyrrolidine-2,4-dicarboxylate induces a large regionally selective and dose-dependent loss of DA neurons and ,-synuclein aggregate formation. These data highlight for the first time the importance of excitatory amino acid carrier 1 function for the maintenance of antioxidant defense in DA neurons and suggest its dysfunction as a candidate mechanism for the selective death of DA neurons such as occurring in Parkinson's disease. [source] Topically Applied Eicosapentaenoic Acid Protects Against Local Immunosuppression Induced by UVB Irradiation, cis -Urocanic Acid and Thymidine Dinucleotides,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2001Ralf M. W. Moison ABSTRACT UVB-induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis -urocanic acid (cis -UCA), but reactive oxygen species (ROS) also plays an important role. Eicosapentaenoic acid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated nature it is susceptible to oxidative damage by ROS. The antioxidant defense system may therefore be challenged upon ultraviolet-B (UVB) irradiation in the presence of EPA. We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis -UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2). The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured. UVB irradiation, cis -UCA and pTpT all caused 70% immunosuppression. Topical pretreatment of mice with EPA partially protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm2 for UVB irradiation, 100 nmol/cm2 for cis -UCA and 1000 nmol/cm2 for pTpT. Higher EPA doses caused higher UVB-induced lipid peroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation. In conclusion, topically applied EPA protects against UVB-, cis -UCA- and pTpT-induced immunosuppression and maintenance of an adequate antioxidant defense seems to be an important prerequisite for the protective action by EPA. [source] CxxS: Fold-independent redox motif revealed by genome-wide searches for thiol/disulfide oxidoreductase functionPROTEIN SCIENCE, Issue 10 2002Dmitri E. Fomenko Abstract Redox reactions involving thiol groups in proteins are major participants in cellular redox regulation and antioxidant defense. Although mechanistically similar, thiol-dependent redox processes are catalyzed by structurally distinct families of enzymes, which are difficult to identify by available protein function prediction programs. Herein, we identified a functional motif, CxxS (cysteine separated from serine by two other residues), that was often conserved in redox enzymes, but rarely in other proteins. Analyses of complete Escherichia coli, Campylobacter jejuni, Methanococcus jannaschii, and Saccharomyces cerevisiae genomes revealed a high proportion of proteins known to use the CxxS motif for redox function. This allowed us to make predictions in regard to redox function and identity of redox groups for several proteins whose function previously was not known. Many proteins containing the CxxS motif had a thioredoxin fold, but other structural folds were also present, and CxxS was often located in these proteins upstream of an ,-helix. Thus, a conserved CxxS sequence followed by an ,-helix is typically indicative of a redox function and corresponds to thiol-dependent redox sites in proteins. The data also indicate a general approach of genome-wide identification of redox proteins by searching for simple conserved motifs within secondary structure patterns. [source] Proteomic analysis of S-nitrosylated proteins in Arabidopsis thaliana undergoing hypersensitive responsePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2008Maria C. Romero-Puertas Abstract Nitric oxide (NO) has a fundamental role in the plant hypersensitive disease resistance response (HR), and S-nitrosylation is emerging as an important mechanism for the transduction of its bioactivity. A key step toward elucidating the mechanisms by which NO functions during the HR is the identification of the proteins that are subjected to this PTM. By using a proteomic approach involving 2-DE and MS we characterized, for the first time, changes in S-nitrosylated proteins in Arabidopsis thaliana undergoing HR. The 16 S-nitrosylated proteins identified are mostly enzymes serving intermediary metabolism, signaling and antioxidant defense. The study of the effects of S-nitrosylation on the activity of the identified proteins and its role during the execution of the disease resistance response will help to understand S-nitrosylation function and significance in plants. [source] Molecular cloning and characterization of ATX1 cDNA from the mole cricket, Gryllotalpa orientalisARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 4 2006Iksoo Kim Abstract To search for an insect homologue of antioxidant protein 1 (ATX1), a mole cricket, Gryllotalpa orientalis, cDNA library was screened and a cDNA clone, which encodes a 73 amino acid polypeptide with a predicted molecular mass of 8.0 kDa and pI of 5.68, was isolated. The G. orientalis ATX1 (GoATX1) cDNA features both a MTCXXC copper-binding site in the N-terminus and a KTGK lysine-rich region in the C-terminus. The deduced amino acid sequence of the GoATX1 cDNA showed 63% identity to Drosophila melanogaster ATX1 and 55% to Ixodes pacificus ATX1. Northern blot analysis revealed the presence of GoATX1 transcripts in midgut, fat body, and epidermis. When H2O2 was injected into the body cavity of G. orientalis adult, GoATX1 mRNA expression was up-regulated in the fat body tissue. Fat body expression level of GoATX1 mRNA in the fat body was increased following exposure to low (4°C) and high (37°C) temperatures, suggesting that GoATX1 plays a protective role against oxidative stress caused by temperature shock. This is the first report about a functional role of insect ATX1 in antioxidant defense. Arch. Insect Biochem. Physiol. 61:231,238, 2006. © 2006 Wiley-Liss, Inc. [source] The importance of gamma-glutamyl transferase in lung glutathione homeostasis and antioxidant defense,BIOFACTORS, Issue 1-4 2003Jyh-Chang Jean First page of article [source] Glutathione deficiency intensifies ischaemia-reperfusion induced cardiac dysfunction and oxidative stressACTA PHYSIOLOGICA, Issue 1 2001S. Leichtweis The efficacy of glutathione (GSH) in protecting ischaemia-reperfusion (I-R) induced cardiac dysfunction and myocardial oxidative stress was studied in open-chest, stunned rat heart model. Female Sprague,Dawley rats were randomly divided into three experimental groups: (1) GSH-depletion, by injection of buthionine sulphoxamine (BSO, 4 mmol kg,1, i.p.) 24 h prior to I-R, (2) BSO injection (4 mmol kg,1, i.p.) in conjunction with acivicin (AT125, 0.05 mmol kg,1, i.v.) infusion 1 h prior to I-R, and (3) control (C), receiving saline treatment. Each group was further divided into I-R, with surgical occlusion of the main left coronary artery (LCA) for 30 min followed by 20 min reperfusion, and sham. Myocardial GSH content and GSH : glutathione disulphide (GSSG) ratio were decreased by ,50% (P < 0.01) in both BSO and BSO + AT125 vs. C. Ischaemia-reperfusion suppressed GSH in both left and right ventricles of C (P < 0.01) and left ventricles of BSO and BSO + AT125 (P < 0.05). Contractility (+dP/dt and ,dP/dt) in C heart decreased 55% (P < 0.01) after I and recovered 90% after I-R, whereas ±dP/dt in BSO decreased 57% (P < 0.01) with ischaemia and recovered 76 and 84% (P < 0.05), respectively, after I-R. For BSO + AT125, ±dP/dt were 64 and 76% (P < 0.01) lower after ischaemia, and recovered only 67 and 61% (P < 0.01) after I-R. Left ventricular systolic pressure in C, BSO and BSO + AT125 reached 95 (P > 0.05) 87 and 82% (P < 0.05) of their respective sham values after I-R. Rate-pressure double product was 11% (P > 0.05) and 25% (P < 0.05) lower in BSO and BSO + AT125, compared with Saline, respectively. BSO and BSO + AT125 rats demonstrated significantly lower liver GSH and heart Mn superoxide dismutase activity than C rats after I-R. These data indicate that GSH depletion by inhibition of its synthesis and transport can exacerbate cardiac dysfunction inflicted by in vivo I-R. Part of the aetiology may involve impaired myocardial antioxidant defenses and whole-body GSH homeostasis. [source] Antioxidant and antimutagenic effects of the crude foliar extract and the alkaloid brachycerine of Psychotria brachycerasENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2007Naíla Cannes do Nascimento Abstract The monoterpene indole alkaloid brachycerine from Psychotria brachyceras has been shown to be induced by UV and to have in vitro antioxidant activity, indicating a possible protective role against the secondary effects of this radiation. In this work, we have studied the antioxidant properties of brachycerine and a crude foliar extract from P. brachyceras by using Saccharomyces cerevisiae strains proficient and deficient in antioxidant defenses. The mutagenic and antimutagenic potential of these substances were assayed in S.cerevisiae N123 strain in the presence and absence of H2O2. In addition, we tested the antioxidant capacity of brachycerine and a crude foliar extract from P. brachyceras on hydroxyl radicals (OH,) using the hypoxanthine/xanthine oxidase assay. The results show that brachycerine and the crude foliar extract of P. brachyceras have antioxidant and antimutagenic effects in yeast and probably this action is mainly due to the scavenging of OH, radicals. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source] Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2009Cristina W. Nogueira Abstract Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4 -induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (, -ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4. Copyright © 2008 John Wiley & Sons, Ltd. [source] Cellular response to oxidative stress: Signaling for suicide and survival,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002Jennifer L. Martindale Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley-Liss, Inc. [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] Neuroprotective effects of bcl-2 overexpression in hippocampal cultures: interactions with pathways of oxidative damageJOURNAL OF NEUROCHEMISTRY, Issue 4 2002Sarah Howard Abstract Overexpression of bcl-2protects neurons from numerous necrotic insults, both in vitro and in vivo. While the bulk of such protection is thought to arise from Bcl-2 blocking cytochrome c release from mitochondria, thereby blocking apoptosis, the protein can target other steps in apoptosis, and can protect against necrotic cell death as well. There is evidence that these additional actions may be antioxidant in nature, in that Bcl-2 has been reported to protect against generators of reactive oxygen species (ROS), to increase antioxidant defenses and to decrease levels of ROS and of oxidative damage. Despite this, there are also reports arguing against either the occurrence, or the importance of these antioxidant actions. We have examined these issues in neuron-enriched primary hippocampal cultures, with overexpression of bcl-2 driven by a herpes simplex virus amplicon: (i) Bcl-2 protected strongly against glutamate, whose toxicity is at least partially ROS-dependent. Such protection involved reduction in mitochondrially derived superoxide. Despite that, Bcl-2 had no effect on levels of lipid peroxidation, which is thought to be the primary locus of glutamate-induced oxidative damage; (ii) Bcl-2 was also mildly protective against the pro-oxidant adriamycin. However, it did so without reducing levels of superoxide, hydrogen peroxide or lipid peroxidation; (iii) Bcl-2 protected against permanent anoxia, an insult likely to involve little to no ROS generation. These findings suggest that Bcl-2 can have antioxidant actions that may nonetheless not be central to its protective effects, can protect against an ROS generator without targeting steps specific to oxidative biochemistry, and can protect in the absence of ROS generation. Thus, the antioxidant actions of Bcl-2 are neither necessary nor sufficient to explain its protective actions against these insults in hippocampal neurons. [source] Evidence that 3-hydroxy-3-methylglutaric acid promotes lipid and protein oxidative damage and reduces the nonenzymatic antioxidant defenses in rat cerebral cortexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2008Guilhian Leipnitz Abstract In the present work we investigated the in vitro effect of 3-hydroxy-3-methylglutarate (HMG) that accumulates in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGLD) on important parameters of oxidative stress in rat cerebral cortex. It was observed that HMG induced lipid peroxidation by significantly increasing chemiluminescence and levels of thiobarbituric acid-reactive substances (TBA-RS). This effect was prevented by the antioxidants ,-tocopherol, melatonin, N-acetylcysteine, and superoxide dismutase plus catalase, suggesting that free radicals were involved in the lipid oxidative damage. On the other hand, HMG did not change TBA-RS levels in intact or disrupted mitochondrial preparations, indicating that generation of oxidants by this organic acid was dependent on cytosolic mechanisms. HMG also induced protein oxidative damage in cortical supernatants, which was reflected by increased carbonyl content and sulfhydryl oxidation. Furthermore, HMG significantly reduced the nonenzymatic antioxidant defenses total-radical trapping antioxidant potential, total antioxidant reactivity, and reduced glutathione (GSH) levels in rat cerebral cortex. HMG-induced GSH reduction was totally blocked by melatonin pretreatment. We also verified that the decrease of GSH levels provoked by HMG in cortical supernatants was not due to a direct oxidative effect of this organic acid, because exposition of commercial GSH and purified membrane protein-bound thiol groups to HMG in the absence of cortical supernatants did not decrease the reduced sulfhydryl groups. Finally, the activities of the main antioxidant enzymes were not altered by HMG exposure. Our data indicate that oxidative stress elicited in vitro by HMG may possibly contribute at least in part to the pathophysiology of the brain injury in HMGLD. © 2007 Wiley-Liss, Inc. [source] Pyruvate protection against ,-amyloid-induced neuronal death: Role of mitochondrial redox stateJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003Gema Alvarez Abstract The mechanism by which ,-amyloid protein (A,) causes degeneration in cultured neurons is not completely understood, but several lines of evidence suggest that A,-mediated neuronal death is associated with an enhanced production of reactive oxygen species (ROS) and oxidative damage. In the present study, we address whether supplementation of glucose-containing culture media with energy substrates, pyruvate plus malate (P/M), protects rat primary neurons from A,-induced degeneration and death. We found that P/M addition attenuated cell death evoked by ,-amyloid peptides (A,25,35 and A,1,40) after 24 hr treatment and that this effect was blocked by ,-ciano-3-hydroxycinnamate (CIN), suggesting that it requires mitochondrial pyruvate uptake. P/M supply to control and A,-treated neuronal cultures increases cellular reducing power, as indicated by the ability to reduce the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The early increases in ROS levels, measured by dichlorofluorescein (DCF) fluorescence, and caspase-3 activity that follow exposure to A, were notably reduced in the presence of P/M. These results place activation of caspase-3 most likely downstream of oxidative damage to the mitochondria and indicate that mitochondrial NAD(P) redox status plays a central role in the neuroprotective effect of pyruvate. Inhibition of respiratory chain complexes and mitochondrial uncoupling did not block the early increase in ROS levels, suggesting that A, could initiate oxidative stress by activating a source of ROS that is not accesible to the antioxidant defenses fueled by mitochondrial substrates. © 2003 Wiley-Liss, Inc. [source] Neuroprotection by melatonin from glutamate-induced excitotoxicity during development of the cerebellum in the chick embryoJOURNAL OF PINEAL RESEARCH, Issue 2 2000Auxiliadora Espinar This work investigated the ability of melatonin to prevent cell damage in the cerebellar cortex of chick embryo caused by glutamate administration. Cell injury was evaluated estimating, at ultrastructural level, the phenomenon of cell death and the synaptogenesis of the Purkinje cells and the cerebellar glomerular synaptic complex. Administration of glutamate during cerebellar development of the chick provokes excitotoxic neuronal degeneration characterized by a phenomenon of neuronal cell death that exhibits essentially the features of a death pattern described as necrosis and the deletion of synaptogenic processes. Our results show that melatonin has a neuroprotective effect against glutamate-induced excitotoxicity. This effect is morphologically revealed by the lack of neural cell death in the embryos treated with melatonin prior to glutamate injection and also by the degree of a synaptogenesis similar to that exhibited by the control group. Likewise, we corroborate the absence of teratological effects of melatonin on chick cerebellar development. Although the possible mechanisms involved in the neuroprotective effect of melatonin are discussed, i.e., direct antioxidant effects, up-regulating endogenous antioxidant defenses, and inhibiting nitric oxide formation activated by glutamate, further studies are required to establish the actual mechanism involved in the neuroprotective effect of melatonin. [source] Ischemia,reperfusion injury pathophysiology, part IJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2004DACVECC, Maureen McMichael DVM Abstract Objective: To review the current scientific literature on ischemia,reperfusion (IR) injury in both human and veterinary medicine. To describe the normal antioxidant defense mechanisms, the pathophysiology of IR injury, and the role of neutrophils in IR injury. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: IR injury is a complex pathophysiological process involving numerous pathways and body systems. Normal antioxidant defense mechanisms function to limit oxidative injury during times of health. Ischemia is the period that occurs before oxygenated blood is re-introduced and the severity of injury has been shown to correlate with the magnitude and length of ischemia in dogs. During ischemia, there is a buildup of substances (i.e., xanthine oxidase, hypoxanthine, etc.) that, upon re-introduction of oxygen, form reactive oxygen species (ROS). ROS, produced in large part upon reperfusion, can cause extensive damage to DNA, proteins, carbohydrates, and lipids. Although mammalian systems are endowed with abundant antioxidant defenses, the generation of large amounts of ROS can overwhelm these mechanisms leading to cell dysfunction and death. Neutrophils play a critical role in IR injury and may mediate the majority of mucosal and microvascular injury that occurs by releasing ROS and proteolytic enzymes. Although experimental studies have been carried out on cats, dogs, and horses there are few clinical studies on companion animals. Conclusions: The pathophysiology of IR injury is complex and involves damage by ROS to all biological membranes. Neutrophils play a major role in IR injury and initiate and propogate much of the damage. This article is intended as a review of the pathophysiology of IR injury. [source] Oxidative stress, chronic disease, and muscle wastingMUSCLE AND NERVE, Issue 4 2007Jennifer S. Moylan PhD Abstract Underlying the pathogenesis of chronic disease is the state of oxidative stress. Oxidative stress is an imbalance in oxidant and antioxidant levels. If an overproduction of oxidants overwhelms the antioxidant defenses, oxidative damage of cells, tissues, and organs ensues. In some cases, oxidative stress is assigned a causal role in disease pathogenesis, whereas in others the link is less certain. Along with underlying oxidative stress, chronic disease is often accompanied by muscle wasting. It has been hypothesized that catabolic programs leading to muscle wasting are mediated by oxidative stress. In cases where disease is localized to the muscle, this concept is easy to appreciate. Transmission of oxidative stress from diseased remote organs to skeletal muscle is thought to be mediated by humoral factors such as inflammatory cytokines. This review examines the relationship between oxidative stress, chronic disease, and muscle wasting, and the mechanisms by which oxidative stress acts as a catabolic signal. Muscle Nerve, 2007 [source] Blocking leukocyte influx and function to prevent chronic lung disease of prematurityPEDIATRIC PULMONOLOGY, Issue 5 2003Richard L. Auten MD Abstract Inflammation is strongly linked to the pathogenesis of chronic lung disease of prematurity (CLD). Premature gas-breathing of ambient or supplemental oxygen in a host with relatively deficient and poorly inducible antioxidant defenses may itself be injurious, and further amplified by mechanical stretch injury in the surfactant-insufficient lung.1 Cellular injury provokes an inflammatory response. Since inflammation is often detected at birth in the lungs of newborns who later develop CLD,2 it has been an attractive strategy to abrogate inflammation, but the arsenal is limited. Glucocorticoids have been widely used but are acknowledged to be potentially harmful to neurologic and somatic development, and are not recommended outside controlled trials.3 The number that benefit is comparable to the number harmed, according to meta-analysis.4 More specific blockade of harmful inflammation could overcome this obstacle. Examination of the inflammatory pathways that initiate and propagate lung injury and subsequent abnormal development points to promising new strategies that may one day be tailored to individual patients. Pediatr Pulmonol. 2003; 35:335,341. © 2003 Wiley-Liss, Inc. [source] Reactive oxygen species and antioxidants in legume nodulesPHYSIOLOGIA PLANTARUM, Issue 4 2000Manuel Becana Reactive oxygen species are a ubiquitous danger for aerobic organisms. This risk is especially elevated in legume root nodules due to the strongly reducing conditions, the high rates of respiration, the tendency of leghemoglobin to autoxidize, the abundance of nonprotein Fe and the presence of several redox proteins that leak electrons to O2. Consequently, nodules are particularly rich in both quantity and diversity of antioxidant defenses. These include enzymes such as superoxide dismutase (EC 1.15.1.1) and ascorbate peroxidase (EC 1.11.1.11) and metabolites such as ascorbate and thiol tripeptides. Nodule antioxidants have been the subject of intensive molecular, biochemical and functional studies that are reviewed here. The emerging theme is that antioxidants are especially critical for the protection and optimal functioning of N2 fixation. We hypothesize that this protection occurs at least at two levels: the O2 diffusion barrier in the nodule parenchyma (inner cortex) and the infected cells in the central zone. [source] Prophylaxis with Centella asiatica confers protection to prepubertal mice against 3-nitropropionic-acid-induced oxidative stress in brainPHYTOTHERAPY RESEARCH, Issue 6 2010George K. Shinomol Abstract While the usage of Centella asiatica (CA) is on the increase worldwide, evidence demonstrating its protective efficacy against neurotoxicants is scarce. Hence the present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of CA against 3-nitropropionic-acid(3-NPA)-induced oxidative stress in the brain of prepubertal mice. We assessed the degree of oxidative stress in cytoplasm of brain regions of male mice (4,wk- old) given CA prophylaxis (5,mg/kg bw) for 10 days followed by 3-NPA administration (i.p.75,mg/kg bw) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the brain of untreated mice as evident by enhanced malondialdehyde levels, reactive oxygen species (ROS) generation, hydroperoxides and protein carbonyls (a measure of protein oxidation) in striatum and other regions (cortex, cerebellum and hippocampus), while CA prophylaxis completely ameliorated the 3-NPA- induced oxidative stress. Depletion of glutathione (GSH) levels, total thiols, perturbations in antioxidant enzymes and cholinergic enzymes in brain discernible among 3-NPA-treated mice were predominantly restored to normalcy with CA prophylaxis. It is hypothesized that the prophylactic protection offered by CA extract against neurotoxicant exposure may be largely due to its ability to enhance GSH, thiols and antioxidant defenses in the brain of prepubertal mice. Copyright © 2009 John Wiley & Sons, Ltd. [source] Functional proteomics of neurokinin B in the placenta indicates a novel role in regulating cytotrophoblast antioxidant defencesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2003Grzegorz Sawicki Abstract Neurokinin B (NKB) has recently been demonstrated to be secreted from the placenta in abnormally high amounts in preeclampsia (PE) and to cause hypertension in rats, suggesting it may be a mediator of some pathophysiological features of PE. It is also known that NKB receptors exist in the placenta. To determine the effect of high levels of NKB on the placenta, we have performed proteomics on five separate preparations of cultured purified human term cytotrophoblast cells. The results showed a statistically significant decrease in 20 proteins, of which five were unknown proteins. Proteins important in antioxidant defenses that decreased were thioredoxin, cyclophilin A, cytokeratin 1, and peroxiredoxin 5. Two proteins that inhibit intravascular anticoagulation, cytokeratin 1 and annexin 11 were also decreased. Pathways involving pro-inflammatory cytokine activation of NF-,B are opposed by Raf kinase inhibitor protein, which was also decreased. Cofilin 1, a protein involved in defense against bacteria, was also decreased. Among other proteins that were suppressed by NKB were proteasome proteins, desmoplakin, and calgizzarin. Western blots confirmed the decrease in cytokeratin 1 and cyclophilin A protein after NKB exposure. In PE, there is reduced antioxidant activity and increased intravascular coagulation. The findings that high levels of NKB, similar to those observed in PE, can impair these two classes of activity support the hypothesis that high NKB levels may contribute to the pathogenesis of PE. [source] | ||||||||||||||||||||||||||||