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Antioxidant Defences (antioxidant + defence)
Terms modified by Antioxidant Defences Selected AbstractsNon-phenolic radical-trapping antioxidantsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2009Mario C. Foti Abstract Objectives The aim of this review article is to introduce the reader to the mechanisms, rates and thermodynamic aspects of the processes involving the most biologically relevant non-phenolic radical-trapping antioxidants. Key findings Antioxidant defences in living organisms rely on a complex interplay between small molecules and enzymes, which cooperate in regulating the concentrations of potentially harmful oxidizing species within physiological limits. The noxious effects of an uncontrolled production of oxygen- and nitrogen-centered radicals are amplified by chain reactions (autoxidations), sustained mainly by peroxyl radicals (ROO,), that oxidize and alter essential biomolecules such as lipids, lipoproteins, proteins and nucleic acids. Summary Non-phenolic antioxidants represent an important and abundant class of radical scavengers in living organisms. These compounds react with peroxyl radicals through various mechanisms: (i) formal H-atom donation from weak X-H bonds (X = O, N, S), as in the case of ascorbic acid (vitamin C), uric acid, bilirubin and thiols; (ii) addition reactions to polyunsaturated systems with formation of C-radicals poorly reactive towards O2, for example ,-carotene and all carotenoids in general; (iii) co-oxidation processes characterized by fast cross-termination reactions, for example ,-terpinene; and (iv) catalytic quenching of superoxide (O2,,) with a superoxide dismutase-like mechanism, for example di-alkyl nitroxides and FeCl3. Kinetic data necessary to evaluate and rationalize the effects of these processes are reported. The mechanisms underlying the pro-oxidant effects of ascorbate and other reducing agents are also discussed. [source] Cytoprotection of beta cells: rational gene transfer strategiesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2006Cillian McCabe Abstract Gene transfer to pancreatic islets may prove useful in preventing islet cell destruction and prolonging islet graft survival after transplantation in patients with type 1 diabetes mellitus (T1DM). Potentially, a host of therapeutically relevant transgenes may be incorporated into an appropriate gene delivery vehicle and used for islet modification. An increasing understanding of the molecular pathogenesis of immune-mediated beta cell death has served to highlight molecules which have become suitable candidates for promoting islet cell survival in the face of oxidative stress. This review aims to give an overview of some conventional gene transfer strategies aimed at promoting islet cell survival in the face of cytokine onslaught. These strategies target three aspects of islet cell physiology: redox status and antioxidant defence, anti-apoptotic gene expression and mediators of cytokine signal transduction pathways. Copyright © 2006 John Wiley & Sons, Ltd. [source] Thiol redox status evaluation in red blood cells by capillary electrophoresis-laser induced fluorescence detectionELECTROPHORESIS, Issue 10 2005Angelo Zinellu Abstract Thiols and in particular glutathione (GSH) play a central role in human metabolism, including the detoxification of xenobiotics, cell homeostasis, radioprotection, and antioxidant defence. Here, a new method is provided for the measurement of reduced and total forms of thiols in red blood cells. In order to minimize oxidation of reduced thiols, a water erythrocyte lysis (15 min at 4°C) was performed followed by a protein precipitation step with acetonitrile. The supernatant was rapidly derivatized with 5-iodoacetoamidefluorescein that trapped thiol groups, thus minimizing auto-oxidation. Derivatized samples were separated in a 57 cm × 75 ,m ID capillary by using 5 mmol/L sodium phosphate, 4 mmol/L boric acid as electrolyte solution with 75 mmol/L N -methyl- D -glucamine at pH 11.0. Under these conditions, cysteinylglycine (CysGly), cysteine (Cys), glutathione, and ,-glutamylcysteine (GluCys) were baseline-resolved in , 4 min. Precision tests showed a good repeatability of our method both for migration times (coefficient of variation CV < 0.8%) and areas (CV < 3.3%). Furthermore, a good reproducibility of intrassay and interassay tests was obtained (CV < 5% and CV < 8%, respectively). The method was employed to investigate the effect of acidic precipitation on intracellular thiol concentration. Our data suggest that sample acidification causes a modification of the measured redox thiol status due to the development of a pro-oxidant environment; moreover, the thiol redox status of red blood cells was evaluated in 22 healthy volunteers. [source] E6* oncoprotein expression of human papillomavirus type-16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defenceEXPERIMENTAL DERMATOLOGY, Issue 6 2005Stéphane Mouret Abstract:, Clinical observations of non-melanoma skin cancer in immunocompromised patients, such as organ transplant recipients, suggest co-operative effects of human papillomavirus (HPV) and ultraviolet (UV) radiation. The aim of the present study is to evaluate UV sensitivity and DNA damage formation according to antioxidant status in HPV16-infected keratinocytes. We used SKv cell lines, infected with HPV16 and well characterized for their proliferative and tumorigenic capacities. We showed that SKv cell lines presented various E6* (a truncated form of E6) RNA levels. We demonstrated that the higher oncoprotein RNA expression level was associated with a higher resistance to solar-simulated radiation, more specifically to UVB radiation and to hydrogen peroxide. Moreover, this high resistance was associated with a low oxidative DNA damage formation after UV radiation and was related to high glutathione content and glutathione peroxidase activities. Therefore, the results of our study suggest that E6* levels could modulate the glutathione/glutathione peroxidase pathway providing a mechanism to protect HPV-infected keratinocytes against an environmental oxidative stress, such as UV radiation. [source] Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxicationJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2005Inmaculada Bando Abstract Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:154,161, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20067 [source] Cyclo(His-Pro) promotes cytoprotection by activating Nrf2-mediated up-regulation of antioxidant defenceJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6 2009Alba Minelli Abstract Hystidyl-proline [cyclo(His-Pro)] is an endogenous cyclic dipeptide produced by the cleavage of thyrotropin releasing hormone. Previous studies have shown that cyclo(His-Pro) protects against oxidative stress, although the underlying mechanism has remained elusive. Here, we addressed this issue and found that cyclo(His-Pro) triggered nuclear accumulation of NF-E2-related factor-2 (Nrf2), a transcription factor that up-regulates antioxidant-/electrophile-responsive element (ARE-EpRE)-related genes, in PC12 cells. Cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion caused by glutamate, rotenone, paraquat and ,-amyloid treatment. Moreover, real-time PCR analyses revealed that cyclo(His-Pro) induced the expression of a number of ARE-related genes and protected cells against hydrogen peroxide-mediated apoptotic death. Furthermore, these effects were abolished by RNA interference-mediated Nrf2 knockdown. Finally, pharmacological inhibition of p-38 MAPK partially prevented both cyclo(His-Pro)-mediated Nrf2 activation and cellular protection. These results suggest that the signalling mechanism responsible for the cytoprotective actions of cyclo(His-Pro) would involve p-38 MAPK activation leading to Nrf2-mediated up-regulation of antioxidant cellular defence. [source] Influence of therapy on the antioxidant status in patients with melanomaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2008V. Gadjeva DSc Summary Background and objective:, Some anticancer drugs can result in increased production of reactive oxygen species (ROS). Alkylating agents are the most frequently used drugs in chemotherapeutic regimens for the treatment of malignant melanoma. It is known that triazenes exhibit in vivo activity by alkylation of nucleic acids and proteins, but there is no data about ROS formation during oxidative metabolism. Single agents of most interest for treatment of malignant melanomas include 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (DTIC) and nitrosoureas such as 1-(2-chloroethyl) -3-cyclohexyl-1-nitrosourea (CCNU), but complete response to these drugs is rare. The present study aimed to determine whether an oxidative stress occurs during the clinical course of melanoma and the influence of therapy on the antioxidant status of patients with melanoma. For this purpose, we investigated plasma concentrations of MDA as indices of the levels of lipid peroxidation products. In addition, we studied the activities of the antioxidant enzymes superoxide dismutases (SOD) and catalase (CAT) in patients with melanoma before any treatment, after surgical removal of melanoma, and after chemotherapy with DTIC or in combination with CCNU of the operated patients. Methods:, Twenty one patients with melanoma were studied. Patients were operated prior to chemotherapy. After recovery for 10,20 days postoperatively, they were studied again for MDA, SOD and CAT activity. The patients were divided into two groups according to the chemotherapy (3,7 treatment cycles): with DTIC , given orally daily for 5 days, every 3 weeks as a single 2200 mg/kg dose and with the combination , DTIC (the same dose) + CCNU , administered orally at a dosage of 120 mg/m2 once every 40 days in accordance with protocols, approved by the Bulgarian Ministry of Health. The total amount of lipid peroxidation products in plasma was assayed. Results and discussion:, Plasma levels of MDA and CAT activity were significantly higher, and erythrocyte SOD activity significantly lower, in patients with melanoma, than in control healthy volunteers (P < 0·0001). Ten to twenty days after surgery, oxidative stress decreased but levels of MDA increased as a result of therapy. Important sources of increased ROS production may be the monocytes, phagocytosis of tumour cells and the cancer tissues. Plasma MDA in patients treated with DTIC + CCNU were significantly higher (P < 0·001), but erythrocyte SOD statistically lower (P < 0·00001), compared with patients treated with DTIC only. However, a combination of DTIC + CCNU did not attenuate oxidative stress, or reduced antioxidant status. Patients treated with this combination are at bigger risk of oxidative injury. Therefore, this disturbance might be due to augmented generation of toxic ROS, possibly from the metabolism of CCNU. Conclusion:, Increased oxidative stress follows an imbalance in antioxidant defence in non-treated patients with melanoma. The impaired antioxidant system favours accumulation of ROS, which may promote the cancer process. After complete removal of melanoma tissues, oxidative stress decreased. The antioxidant status of melanoma patients operated on was influenced by the different chemotherapeutic regimens used and may play an important role in the response. Patients on DTIC + CCNU are at higher risk of oxidative injury. This drug combination probably exerts its toxic activity by ROS, which could be products of the metabolism of CCNU. [source] A glutamate-alanine-leucine (EAL) domain protein of Salmonella controls bacterial survival in mice, antioxidant defence and killing of macrophages: role of cyclic diGMPMOLECULAR MICROBIOLOGY, Issue 5 2005Katherine B. Hisert Summary Signature-tagged transposon mutagenesis of Salmonella with differential recovery from wild-type and immunodeficient mice revealed that the gene here named cdgR[for c-diguanylate (c-diGMP) regulator] is required for the bacterium to resist host phagocyte oxidase in vivo. CdgR consists solely of a glutamate-alanine-leucine (EAL) domain, a predicted cyclic diGMP (c-diGMP) phosphodiesterase. Disruption of cdgR decreased bacterial resistance to hydrogen peroxide and accelerated bacterial killing of macrophages. An ultrasensitive assay revealed c-diGMP in wild-type Salmonella with increased levels in the CdgR-deficient mutant. Thus, besides its known role in regulating cellulose synthesis and biofilm formation, bacterial c-diGMP also regulates host,pathogen interactions involving antioxidant defence and cytotoxicity. [source] Enteric neurodegeneration in ageingNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2008M. Camilleri Abstract, The objective of this article is to review the clinical presentation and neurobiology of degeneration of the enteric nervous system with emphasis on human data where available. Constipation, incontinence and evacuation disorders are frequently encountered in the ageing population. Healthy lower gastrointestinal function is essential for successful ageing as it is critical to maintaining independence and autonomy to pursue further activity. One clinical expression of enteric neurodegeneration is constipation. However, the aetiology may be multifactorial as disturbances of epithelial, muscle or neural function may all result from neurodegeneration. There is evidence of loss of excitatory (e.g. cholinergic) enteric neurons and interstitial cells of Cajal, whereas inhibitory (including nitrergic) neurons appear unaffected. Understanding neurodegeneration in the enteric nervous system is key to developing treatments to reverse it. Neurotrophins have been shown to accelerate colonic transit and relieve constipation in the medium term; they are also implicated in maintenance programmes in adult enteric neurons through a role in antioxidant defence. However, their effects in ageing colon require further study. There is evidence that 5-HT2 and 5-HT4 mechanisms are involved in development, maintenance and survival of enteric neurons. Further research is needed to understand and potentially reverse enteric neurodegeneration. [source] Production, localisation and possible roles of nitric oxide in drought-stressed grapevinesAUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 1 2010A.A. PATAKAS Abstract Background and Aims:, The aim of this study was to monitor nitric oxide (NO) production in response to progressive soil drying as well as to evaluate its possible role as an intermolecular signalling molecule mediating drought-stress responses in grapevines. Methods and Results:, NO production in response to water stress was examined in potted grapevine plants (Vitis vinifera L. cv. Mavrodafni). The cellular sites of NO production and localisation in stressed plants were monitored by fluorometric techniques. Results indicated that both abscisic acid and NO concentrations increased significantly in leaves of stressed plants. The stomatal guard cells seemed to be the sites of earlier NO accumulation. The changes in stomatal conductance seemed to be closely related to both abscisic acid and NO increase, while there was no significant correlation between stomatal conductance and hydrogen peroxide concentration. Conclusions:, The close relationships between stomatal conductance and NO concentrations indicate a potential role of this molecule in drought-signalling pathway in grapevines. Significance of the Study:, Results suggest a contribution of hydrogen peroxide to triggering NO production as well as a possible role of NO on both stomatal closure and antioxidant defence in drought-stressed grapevines. [source] C. elegans knockouts in ubiquinone biosynthesis genes result in different phenotypes during larval developmentBIOFACTORS, Issue 1-4 2005ÁNgela Gavilán Abstract Ubiquinone is an essential molecule in aerobic organisms to achieve both, ATP synthesis and antioxidant defence. Mutants in genes responsible of ubiquinone biosynthesis lead to non-respiring petite yeast. In C. elegans, coq-7/clk-1 but not coq-3 mutants live longer than wild type showing a ,slowed' phenotype. In this paper we demonstrate that absence in ubiquinone in coq-1, coq-2 or coq-8 mutants lead to larval development arrest, slowed pharyngeal pumping, eventual paralysis and cell death. All these features emerge during larval development, whereas embryo development appeared similar to that of wild type individuals. Dietary coenzyme Q did not restore any of the alterations found in these coq mutants. These phenomena suggest that coenzyme Q mutants unable to synthesize this molecule develop a deleterious phenotype leading to lethality. On the contrary, phenotype of C. elegans coq-7/clk-1 mutants may be a unique phenotype than can not generalize to mutants in ubiquinone biosynthesis. This particular phenotype may not be based on the absence of endogenous coenzyme Q, but to the simultaneous presence of dietary coenzyme Q and the its biosynthesis intermediate demethoxy-coenzyme Q. [source] Type 1 diabetes: can exercise impair the autoimmune event?CELL BIOCHEMISTRY AND FUNCTION, Issue 4 2008The L -arginine/glutamine coupling hypothesis Abstract Prevention of type 1 diabetes mellitus (T1DM) requires early intervention in the autoimmune process directed against ,-cells of the pancreatic islets of Langerhans, which is believed to result from a disorder of immunoregulation. According to this concept, a T-helper lymphocyte of type 1 (Th1) subset of T-lymphocytes and their cytokine products, the type 1 cytokines [e.g. interleukin 2 (IL-2), interferon gamma (IFN-,) and tumour necrosis factor beta (TNF-,)] prevail over immunoregulatory (anti-inflammatory) Th2 subset and its cytokine products, i.e. type 2 cytokines (e.g. IL-4, IL-6 and IL-10). This allows type 1 cytokines to initiate a cascade of immune/inflammatory processes in the islet (insulitis), culminating in ,-cell destruction. Activation of sympathetic-corticotropin-releasing hormone (CRH) axis by psychological stress induces specifically Th1 cell overactivity that determines enhanced glutamine utilization and consequent poor L -arginine supply for nitric oxide (NO)-assisted insulin secretion. This determines the shift of intraislet glutamate metabolism from the synthesis of glutathione (GSH) to that of L -arginine, leading to a redox imbalance that activates nuclear factor ,B exacerbating inflammation and NO-mediated cytotoxicity. Physical exercise is capable of inducing changes in the pattern of cytokine production and release towards type 2 class and to normalize the glutamine supply to the circulation, which reduces the need for glutamate, whose metabolic fate may be restored in the direction of GSH synthesis and antioxidant defence. Also, the 70-kDa heat shock protein (hsp70), which is immunoregulatory, may modulate exercise-induced anti-inflammation. In this work, we envisage how exercise can intervene in the mechanisms involved in the autoimmune process against ,-cells and how novel therapeutic approaches may be inferred from these observations. Copyright © 2008 John Wiley & Sons, Ltd. [source] Increased susceptibility to oxidative stress as a proximate cost of reproductionECOLOGY LETTERS, Issue 5 2004Carlos Alonso-Alvarez Abstract In iteroparous species high investment in current reproduction is usually paid in terms of reduced future reproduction and increased mortality. However, the proximal mechanisms of these costs remain poorly understood. Free radicals arising as by-products of normal metabolic activities have deleterious effects on cellular proteins, lipids and DNA, and this phenomenon is known as oxidative stress. Since reproduction is an energetically demanding activity, which increases both basal and field metabolic rates, one could expect that breeding effort generates an oxidative stress whose strength depends on the availability and efficiency of antioxidant defences. In agreement with this prediction, we show here for the first time that reproduction decreases antioxidant defences, illustrating that oxidative stress represents a cost of reproduction. We suggest that increased susceptibility to oxidative stress might be a general proximal connection between reproduction and survival underlying other mechanistic links previously acknowledged. [source] Evidence supporting an increased presence of reactive oxygen species in the diseased equine jointEQUINE VETERINARY JOURNAL, Issue 5 2000A. N. Dimock Summary Reactive oxygen species (ROS) are capable of degrading many components of the joint in the presence of insufficient antioxidant defences, and as a result have been implicated in the pathogenesis of joint disease in horses. However, to our knowledge, evidence of ROS occurring in diseased joints of horses has not been reported. The objective of this experiment was to compare differences in synovial fluid protein carbonyl content (as a marker of oxidative modification of synovial fluid proteins by ROS) and the antioxidant status of synovial fluid between clinically normal and diseased equine joints. Synovial fluid was collected from the metacarpophalangeal, metatarsophalangeal, carpal and tarsal joints of 4 horses, age 2,5 years, as controls, and from diseased joints (metacarpophalangeal, metatarsophalangeal, carpal, tarsal and/or femoropatellar) of 61 horses, age 2,5 years. Synovial fluid protein carbonyl content was higher (P<0.01) in diseased joints as compared to controls. Antioxidant status of synovial fluid from diseased joints was higher, but not significantly, than that of controls (P = 0.0595). These findings require further study to determine their contribution to the overall disease process. [source] Oxidative stress in cyanobacteriaFEMS MICROBIOLOGY REVIEWS, Issue 2 2009Amel Latifi Abstract Reactive oxygen species (ROS) are byproducts of aerobic metabolism and potent agents that cause oxidative damage. In oxygenic photosynthetic organisms such as cyanobacteria, ROS are inevitably generated by photosynthetic electron transport, especially when the intensity of light-driven electron transport outpaces the rate of electron consumption during CO2 fixation. Because cyanobacteria in their natural habitat are often exposed to changing external conditions, such as drastic fluctuations of light intensities, their ability to perceive ROS and to rapidly initiate antioxidant defences is crucial for their survival. This review summarizes recent findings and outlines important perspectives in this field. [source] Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic ratINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2007B. Shrilatha Summary Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione- S -transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats. [source] DNA damage in metabolic syndrome and its association with antioxidative and oxidative measurementsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2006R. DEMIRBAG Summary The purpose of this study was to assess DNA damage levels in subjects with metabolic syndrome (MetS). Sixty-five subjects with MetS and 65 controls were enrolled in this study. Levels of DNA damage, total antioxidant capacity (TAC), total peroxide and oxidative stress index (OSI) were measured. We found that DNA damage levels were significantly increased [155.5 (60,264) vs. 93.2 (0,208) arbitrary units; p < 0.001] and TAC levels were significantly decreased in MetS than in control (1.34 ± 0.27 vs. 55 ± 0.33 mmol Trolox equivalent/l; p < 0.001). A significant falling trend in TAC levels and a significant rising trend in DNA damage values with the increase in the number of metabolic disturbances (anova p < 0.001 for both) were observed. Total peroxide (30.9 ± 4.9 vs. 21.3 ± 2.5 ,mol H2O2/l; p < 0.001) and OSI levels [2.4 (1.3,3.8) vs. 1.4 (0.7,2.3) arbitrary units; p < 0.001] were significantly higher in the subjects with MetS than in controls. We found significant negative correlation between DNA damage and TAC levels in MetS (r = ,0.656, p < 0.001) and in control (r = ,0.546, p < 0.001). In multiple linear regression analysis, age, body mass index, presence of MetS and number of the componens of MetS were independent predictors of log-transformed DNA damage (p < 0.05, for all). DNA damage is increased in patients with MetS. The increase in DNA damage might be occur because of the increase in the imbalance between the production of oxidants and antioxidant defences in subjects with MetS. [source] Mitochondrial Oxidative Stress Plays a Key Role in Aging and ApoptosisIUBMB LIFE, Issue 5 2000Juan Sastre Abstract Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the ageassociated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. [source] Comparison of mitochondrial ascorbate peroxidase in the cultivated tomato, Lycopersicon esculentum, and its wild, salt-tolerant relative, L. pennellii, a role for matrix isoforms in protection against oxidative damagePLANT CELL & ENVIRONMENT, Issue 2 2004V. MITTOVA ABSTRACT Mitochondria require robust antioxidant defences to prevent lipid peroxidation and to protect tricarboxylic acid cycle enzymes from oxidative damage. Mitochondria from wild, salt-tolerant tomato, Lycopersicon pennellii (Lpa) did not exhibit lipid peroxidation in response to high salinity (100 mm NaCl), whereas those isolated from cultivated tomato, L. esculentum (Lem), accumulated malondialdehyde. The activity, intraorganellar distribution and salt response of mitochondrial ascorbate peroxidase (mAPX) differed dramatically in the two species. In Lem mitochondria, the majority (84%) of mAPX was associated with membranes, being located either on the inner membrane, facing the intermembrane space, or on the outer membrane. Total mAPX activity did not increase substantially in response to salt, although the proportion of matrix APX increased. In contrast, 61% of Lpa mAPX activity was soluble in the matrix, the remainder being bound to the matrix face of the inner membrane. Salt treatment increased the activity of all mAPX isoforms in Lpa, without altering their intramitochondrial distribution. The membrane-bound isoforms were detected in mitochondria of both species by western blotting and found to be induced by salt in Lpa. These observations suggest that matrix-associated APX isoforms could act in concert with other mitochondrial antioxidants to protect against salt-induced oxidative stress. [source] Short-term antioxidant supplementation reduces oxidative stress in elderly patients with type 2 diabetes mellitus,a pilot studyPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 7 2002SL Nuttall PhD Research Fellow Abstract Aims The aim of this pilot study was to determine what dose of which antioxidants might be studied in clinical trials by assessing the impact of vitamin (C and E) supplementation on markers of oxidative stress and LDL subfractions in patients with type 2 diabetes mellitus. Methods Nine elderly patients with type 2 diabetes took a moderate dose combination of vitamins C (500 mg) and E (400 IU) for 4 weeks. Following a 4 week washout, the patients had a further 4 weeks of supplementation with a higher dose combination of vitamins C (1000 mg) and E (800 IU). Blood was sampled pre- and post-supplementation for vitamin E by high-performance liquid chromatography (HPLC), total antioxidant capacity by enhanced chemiluminescence, total cholesterol and lipid hydroperoxides by colour spectrophotometry and LDL subfraction profile by disc polyacrylamide gel electrophoresis. Results Vitamin E was increased, after the moderate dose combination (59.8 ± 6 versus 36.4 ± 4 µmol/L, p < 0.001) and increased further by the higher dose (72.7 ± 11 versus 30.8 ± 5 µmol/L, p < 0.001). Total antioxidant capacity was significantly increased above baseline after both doses (508.2 ± 33 versus 436.4 ± 31, p < 0.01 (moderate); 519.3 ± 48 versus 440.8 ± 34 µmol/L trolox eq., p < 0.01 (high)). Lipid hydroperoxides were reduced more after the moderate dose combination than after the high dose (6.1 ± 1 versus 12.1 ± 2, p < 0.01; 8.0 ± 1 versus 11.6 ± 1 µmol/L, p < 0.05). LDL subfraction score showed a non-significant reduction after both periods of supplementation. Conclusions This study has demonstrated that supplementation with modest doses of the antioxidant vitamins C and E can significantly increase antioxidant defences and reduce oxidative damage in elderly patients with type 2 diabetes. Copyright © 2002 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] Mitochondrial formation of reactive oxygen speciesTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003Julio F. Turrens The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2,,). Even though O2,, is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants. [source] Effects of in vitro exposure to ozone and/or hyperoxia on superoxide dismutase, catalase, glutathione and lipid peroxidation in red blood cells and plasma of rainbow trout, Oncorhynchus mykiss (Walbaum)AQUACULTURE RESEARCH, Issue 3 2002O Ritola Abstract In aquaculture, ozone is used as a disinfectant. In its production, extensive amounts of oxygen are formed resulting in hyperoxic conditions in culture units. Both ozone and hyperoxia have the potential to be toxic via pro-oxidant mechanisms and to activate antioxidant defence systems in cultured species. To eliminate systemic effects, blood of rainbow trout, Oncorhynchus mykiss (Walbaum), was exposed in vitro for 5 min to ozone/hyperoxia or hyperoxia, and changes in antioxidant defences and lipid peroxidation were measured after exposure. Ozone exposure caused severe damage in red blood cells (rbc) detected as increased lipid peroxidation and oxidized glutathione (GSSG) levels in both plasma and rbc. Oxygen exposure alone increased intracellular lipid peroxidation and GSSG levels 10 min after exposure and was not evident in the plasma at any time. Ozone, but not oxygen exposure, decreased reduced glutathione (GSH) levels in plasma, and the changes were negatively correlated with increased lipid peroxidation in rbc, indicating that extracellular GSH has a dynamic role in the protection of rbc from direct oxidation by ozone. Both ozone and hyperoxic conditions increased superoxide dismutase (SOD) activity in rbc 3 and 6 h after exposure. In contrast, catalase activity was only increased 10 min after oxygen exposure, suggesting other catalase activation mechanisms rather than enzyme induction. The recovery of lipid peroxidation and GSSG levels in rbc after hyperoxia, but not ozone exposure, indicated a capacity to defend against hyperoxia-produced oxidative damage, but an overwhelming of antioxidant defences by ozone in rainbow trout rbc in vitro. [source] A central role of eNOS in the protective effect of wine against metabolic syndromeCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2006Federico Leighton Abstract The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10,30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic syndrome. This hypothesis is supported by epidemiological observations and needs experimental validation in human intervention studies. Copyright © 2005 John Wiley & Sons, Ltd. [source] Ethanolic leaf extract of neem (Azadirachta indica) inhibits buccal pouch carcinogenesis in hamstersCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2005R. Subapriya Abstract We evaluated the chemopreventive effects of ethanolic neem leaf extract in the initiation and post-initiation phases of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The frequency of bone marrow micronuclei as well as the concentrations of lipid peroxides, ratio of reduced to oxidized glutathione (GSH/GSSG), and the activities of the GSH-dependent enzymes glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in the buccal pouch, liver and erythrocytes were used as biomarkers of chemoprevention. All the hamsters painted with DMBA alone for 14 weeks developed buccal pouch carcinomas that showed diminished lipid peroxidation and enhanced antioxidant status associated with increased frequencies of bone marrow micronuclei. In the liver and erythrocytes of tumour-bearing animals, enhanced lipid peroxidation was accompanied by compromised antioxidant defences. Administration of ethanolic neem leaf extract effectively suppressed DMBA-induced HBP carcinogenesis as revealed by the absence of tumours in the initiation phase and reduced tumour incidence in the post-initiation phase. In addition, ethanolic neem leaf extract modulated lipid peroxidation and enhanced antioxidant status in the pouch, liver and erythrocytes and reduced the incidence of bone marrow micronuclei. The results of the present study, demonstrate that ethanolic neem leaf extract inhibits the development of DMBA-induced HBP tumours by protecting against oxidative stress. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||||||||