Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Metallothionein-I/II Knockout Mice Aggravate Mitochondrial Superoxide Production and Peroxiredoxin 3 Expression in Thyroid after Excessive Iodide Exposure Mon, 25 May 2015 07:34:31 +0000 http://www.hindawi.com/journals/omcl/2015/267027/ Purpose. We aim to figure out the effect of metallothioneins on iodide excess induced oxidative stress in the thyroid. Methods. Eight-week-old MT-I/II knockout (MT-I/II KO) mice and background-matched wild-type (WT) mice were used. Mitochondrial superoxide production and peroxiredoxin (Prx) 3 expression were measured. Results. In in vitro study, more significant increases in mitochondrial superoxide production and Prx 3 expression were detected in the MT-I/II KO groups. In in vivo study, significantly higher concentrations of urinary iodine level were detected in MT-I/II KO mice in 100 HI group. Compared to the NI group, there was no significant difference existing in serum thyroid hormones level in either groups (), while the mitochondrial superoxide production was significantly increased in 100 HI groups with significantly increased LDH activity and decreased relative cell viability. Compared to WT mice, more significant changes were detected in MT-I/II KO mice in 100 HI groups. No significant differences were detected between the NI group and 10 HI group in both the MT-I/II KO and WT mice groups (). Conclusions. Iodide excess in a thyroid without MT I/II protection may result in strong mitochondrial oxidative stress, which further leads to the damage of thyrocytes. Na Zhang, Lingyan Wang, Qi Duan, Laixiang Lin, Mohamed Ahmed, Tingting Wang, and Xiaomei Yao Copyright © 2015 Na Zhang et al. All rights reserved. Immunohistochemical Study of Nrf2-Antioxidant Response Element as Indicator of Oxidative Stress Induced by Cadmium in Developing Rats Mon, 25 May 2015 07:12:23 +0000 http://www.hindawi.com/journals/omcl/2015/570650/ In developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reported in vitro and in situ cells. In this study we evaluated the morphological changes and the expression pattern of Nrf2 and correlated them with the Cd concentrations in different ages of developing rats in heart, lung, kidney, liver, and brain. The Cd content in different organs of rats treated with the metal was increased in all ages assayed. Comparatively, lower Cd brain levels were found in rats intoxicated at the age of 12 days, then pups treated at 5, 10, or 15 days old, at the same metal dose. No evident changes, as a consequence of cadmium exposure, were evident in the morphological analysis in any of the ages assayed. However, Nrf2-ARE immunoreactivity was observed in 15-day-old rats exposed to Cd. Our results support that fully developed blood-brain barrier is an important protector against Cd entrance to brain and that Nrf2 increased expression is a part of protective mechanism against cadmium-induced toxicity. Sergio Montes, Daniel Juárez-Rebollar, Concepción Nava-Ruíz, Aurora Sánchez-García, Yesica Heras-Romero, Camilo Rios, and Marisela Méndez-Armenta Copyright © 2015 Sergio Montes et al. All rights reserved. Ceramides in Alzheimer’s Disease: Key Mediators of Neuronal Apoptosis Induced by Oxidative Stress and Aβ Accumulation Sun, 24 May 2015 11:26:20 +0000 http://www.hindawi.com/journals/omcl/2015/346783/ Alzheimer’s disease (AD), the most common chronic and progressive neurodegenerative disorder, is characterized by extracellular deposits of amyloid β-peptides (Aβ) and intracellular deposits of hyperphosphorylated tau (phospho-tau) protein. Ceramides, the major molecules of sphingolipid metabolism and lipid second messengers, have been associated with AD progression and pathology via Aβ generation. Enhanced levels of ceramides directly increase Aβ through stabilization of β-secretase, the key enzyme in the amyloidogenic processing of Aβ precursor protein (APP). As a positive feedback loop, the generated oligomeric and fibrillar Aβ induces a further increase in ceramide levels by activating sphingomyelinases that catalyze the catabolic breakdown of sphingomyelin to ceramide. Evidence also supports important role of ceramides in neuronal apoptosis. Ceramides may initiate a cascade of biochemical alterations, which ultimately leads to neuronal death by diverse mechanisms, including depolarization and permeabilization of mitochondria, increased production of reactive oxygen species (ROS), cytochrome c release, Bcl-2 depletion, and caspase-3 activation, mainly by modulating intracellular signalling, particularly along the pathways related to Akt/PKB kinase and mitogen-activated protein kinases (MAPKs). This review summarizes recent findings related to the role of ceramides in oxidative stress-driven neuronal apoptosis and interplay with Aβ in the cascade of events ending in neuronal degeneration. Maja Jazvinšćak Jembrek, Patrick R. Hof, and Goran Šimić Copyright © 2015 Maja Jazvinšćak Jembrek et al. All rights reserved. Protective Effects of Hydrogen-Rich Saline on Rats with Smoke Inhalation Injury Thu, 21 May 2015 11:29:06 +0000 http://www.hindawi.com/journals/omcl/2015/106836/ Objective. To explore the protective effects of hydrogen-rich saline on rats with smoke inhalation injury. Methods. 36 healthy male Sprague-Dawley rats were randomly divided into 3 groups ( per group): sham group (S), inhalation injury plus normal saline treatment group (I+NS), and inhalation injury plus hydrogen-rich saline treatment group (I+HS). 30 min after injury, normal saline and hydrogen-rich saline were injected intraperitoneally (5 mL/kg) in I+NS group and I+HS group, respectively. All rats were euthanized and blood and organ specimens were collected for determination 24 h after inhalation injury. Results. Tumor necrosis factor-alpha (TNF-α) levels, malondialdehyde (MDA) concentrations, nuclear factor kappa B (NF-κB) p65 expression, and apoptosis index (AI) in I+HS group were significantly decreased (), while superoxide dismutase (SOD) activities were increased compared with those in I+NS group; and a marked improvement in alveolar structure was also found after hydrogen-rich saline treatment. Conclusions. Hydrogen-rich saline treatment exerts protective effects in acute lung injury induced by inhalation injury, at least in part through the activation of anti-inflammatory and antioxidant pathways and inhibition of apoptosis. Xing Chen, Qi Liu, Dawei Wang, Shihai Feng, Yongjian Zhao, Yun Shi, and Qun Liu Copyright © 2015 Xing Chen et al. All rights reserved. Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement Thu, 21 May 2015 06:30:18 +0000 http://www.hindawi.com/journals/omcl/2015/976908/ Alzheimer’s disease (AD) is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se) in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25–35; 3 nmol/3 μL) or distilled water was administered via intracerebroventricular (i.c.v.) injection. Selenofuranoside (5 mg/kg) or vehicle (canola oil) was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM) and step-down passive-avoidance (SDPA) tests. Antioxidant defenses along with reactive species (RS) were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies. Cristiano Chiapinotto Spiazzi, Melina Bucco Soares, Aryele Pinto Izaguirry, Laura Musacchio Vargas, Mariane Magalhães Zanchi, Natasha Frasson Pavin, Ricardo Ferreira Affeldt, Diogo Seibert Lüdtke, Marina Prigol, and Francielli Weber Santos Copyright © 2015 Cristiano Chiapinotto Spiazzi et al. All rights reserved. Generation of Adducts of 4-Hydroxy-2-nonenal with Heat Shock 60 kDa Protein 1 in Human Promyelocytic HL-60 and Monocytic THP-1 Cell Lines Wed, 20 May 2015 16:40:07 +0000 http://www.hindawi.com/journals/omcl/2015/296146/ Heat shock 60 kDa protein 1 (HSP60) is a chaperone and stress response protein responsible for protein folding and delivery of endogenous peptides to antigen-presenting cells and also a target of autoimmunity implicated in the pathogenesis of atherosclerosis. By two-dimensional electrophoresis and mass spectrometry, we found that exposure of human promyelocytic HL-60 cells to a nontoxic concentration (10 μM) of 4-hydroxy-2-nonenal (HNE) yielded a HSP60 modified with HNE. We also detected adducts of HNE with putative uncharacterized protein CXorf49, the product of an open reading frame identified in various cell and tissue proteomes. Moreover, exposure of human monocytic THP-1 cells differentiated with phorbol 12-myristate 13-acetate to 10 μM HNE, and to light density lipoprotein modified with HNE (HNE-LDL) or by copper-catalyzed oxidation (oxLDL), but not to native LDL, stimulated the formation of HNE adducts with HSP60, as detected by immunoprecipitation and western blot, well over basal levels. The identification of HNE-HSP60 adducts outlines a framework of mutually reinforcing interactions between endothelial cell stressors, like oxLDL and HSP60, whose possible outcomes, such as the amplification of endothelial dysfunction, the spreading of lipoxidative damage to other proteins, such as CXorf49, the activation of antigen-presenting cells, and the breaking of tolerance to HSP60 are discussed. Alessia Arcaro, Martina Daga, Giovanni Paolo Cetrangolo, Eric Stefano Ciamporcero, Alessio Lepore, Stefania Pizzimenti, Claudia Petrella, Maria Graf, Koji Uchida, Gianfranco Mamone, Pasquale Ferranti, Paul R. J. Ames, Giuseppe Palumbo, Giuseppina Barrera, and Fabrizio Gentile Copyright © 2015 Alessia Arcaro et al. All rights reserved. Role of Oxidative RNA Damage in Chronic-Degenerative Diseases Wed, 20 May 2015 14:32:40 +0000 http://www.hindawi.com/journals/omcl/2015/358713/ Normal cellular metabolism and exposure to ionizing and ultraviolet radiations and exogenous agents produce reactive oxygen species (ROS). Due to their reactivity, they can interact with many critical biomolecules and induce cell damage. The reaction of ROS with free nucleobases, nucleosides, nucleotides, or oligonucleotides can generate numerous distinct modifications in nucleic acids. Oxidative damage to DNA has been widely investigated and is strongly implicated in the development of many chronic-degenerative diseases. In contrast, RNA damage is a poorly examined field in biomedical research. In this review, I discuss the importance of RNA as a target of oxidative damage and the role of oxidative damage to RNA in the pathogenesis of some chronic-degenerative diseases, such as neurological disorders, atherosclerosis, and cancer. Furthermore, I review recent evidence suggesting that RNA may be the target for toxic agents and indicating RNA degradation as a powerful tool to treat any pathology in which there is an aberrant expression of mRNA and/or its gene products. Carmela Fimognari Copyright © 2015 Carmela Fimognari. All rights reserved. Markers of Oxidative Stress and Neuroprogression in Depression Disorder Wed, 20 May 2015 12:06:05 +0000 http://www.hindawi.com/journals/omcl/2015/898393/ Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed. Magdaléna Vaváková, Zdeňka Ďuračková, and Jana Trebatická Copyright © 2015 Magdaléna Vaváková et al. All rights reserved. Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression Wed, 20 May 2015 07:09:15 +0000 http://www.hindawi.com/journals/omcl/2015/654594/ Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-β and ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-β can control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-β signaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-β and ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation but also may collaborate in cancer progression. The mutual collaboration of TGF-β and ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies. Jelena Krstić, Drenka Trivanović, Slavko Mojsilović, and Juan F. Santibanez Copyright © 2015 Jelena Krstić et al. All rights reserved. Treatment of β-Thalassemia/Hemoglobin E with Antioxidant Cocktails Results in Decreased Oxidative Stress, Increased Hemoglobin Concentration, and Improvement of the Hypercoagulable State Tue, 19 May 2015 13:51:15 +0000 http://www.hindawi.com/journals/omcl/2015/537954/ Studies on the antioxidant treatment for thalassemia have reported variable outcomes. However, treatment of thalassemia with a combination of hydrophobic and hydrophilic antioxidants and an iron chelator has not been studied. This study investigated the effects of antioxidant cocktails for the treatment of β-thalassemia/hemoglobin E (HbE), which is the most common form of β-thalassemia in Southeast Asia. Sixty patients were divided into two groups receiving N-acetylcysteine, deferiprone, and either curcuminoids (CUR) or vitamin E (Vit-E), and their hematological parameters, iron load, oxidative stress, and blood coagulation potential were evaluated. Patients were classified as responders if they showed the improvements of the markers of iron load and oxidative stress, otherwise as nonresponders. During treatment, the responders in both groups had significantly decreased iron load, oxidative stress, and coagulation potential and significantly increased antioxidant capacity and hemoglobin concentration. The significantly maximum increase in hemoglobin concentration was 11% at month 4 in CUR group responders and 10% at month 10 in Vit-E group responders. In conclusion, the two antioxidant cocktails can improve anemia, iron overload, oxidative stress, and hypercoagulable state in β-thalassemia/HbE. Orn-uma Yanpanitch, Suneerat Hatairaktham, Ratiya Charoensakdi, Narumol Panichkul, Suthat Fucharoen, Somdet Srichairatanakool, Noppadol Siritanaratkul, and Ruchaneekorn W. Kalpravidh Copyright © 2015 Orn-uma Yanpanitch et al. All rights reserved. Vitamin A and Retinoids as Mitochondrial Toxicants Tue, 19 May 2015 11:31:26 +0000 http://www.hindawi.com/journals/omcl/2015/140267/ Vitamin A and its derivatives, the retinoids, are micronutrient necessary for the human diet in order to maintain several cellular functions from human development to adulthood and also through aging. Furthermore, vitamin A and retinoids are utilized pharmacologically in the treatment of some diseases, as, for instance, dermatological disturbances and some types of cancer. In spite of being an essential micronutrient with clinical application, vitamin A exerts several toxic effects regarding redox environment and mitochondrial function. Moreover, decreased life quality and increased mortality rates among vitamin A supplements users have been reported. However, the exact mechanism by which vitamin A elicits its deleterious effects is not clear yet. In this review, the role of mitochondrial dysfunction in the mechanism of vitamin A-induced toxicity is discussed. Marcos Roberto de Oliveira Copyright © 2015 Marcos Roberto de Oliveira. All rights reserved. Integrated Haematological Profiles of Redox Status, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome Mon, 18 May 2015 06:55:39 +0000 http://www.hindawi.com/journals/omcl/2015/490613/ The pathogenesis of obesity (OB) and metabolic syndrome (MetS) implies free radical-, oxidized lipid- (LOOH-), and inflammatory cytokine-mediated altered pathways in target organs. Key elements of the transition from benign OB to unhealthy OB+MetS remain unclear. Here, we measured a panel of redox, antioxidant, and inflammation markers in the groups of OB patients (67 with, 45 without MetS) and 90 controls. Both OB groups displayed elevated levels of adipokines and heavy oxidative stress (OS) evidenced by reduced levels of glutathione, downregulated glutathione-S-transferase, increased 4-hydroxynonenal-protein adducts, reactive oxygen species, and membrane-bound monounsaturated fatty acids (MUFA). Exclusively in OB+MetS, higher-than-normal glutathione peroxidase activity, tumor necrosis factor-α, and other proinflammatory cytokines/chemokines/growth factors were observed; a combination of high adipokine plasminogen activator inhibitor-1 and MUFA was consistent with increased cardiovascular risk. The uncomplicated OB group showed features of adaptation to OS such as decreased levels of vitamin E, activated superoxide dismutase, and inhibited catalase, suggesting H2O2 hyperproduction. Proinflammatory cytokine pattern was normal, except few markers like RANTES, a suitable candidate for therapeutic approaches to prevent a setting of MetS by inhibition of LOOH-primed leukocyte chemotaxis/recruitment to target tissues. Carla Lubrano, Giuseppe Valacchi, Palma Specchia, Lucio Gnessi, Elizaveta P. Rubanenko, Elena A. Shuginina, Arseny I. Trukhanov, Liudmila G. Korkina, and Chiara De Luca Copyright © 2015 Carla Lubrano et al. All rights reserved. Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress Sun, 17 May 2015 07:35:45 +0000 http://www.hindawi.com/journals/omcl/2015/150829/ Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect of α-tocopherol, α-, δ-, and γ-tocotrienols and a tocotrienol rich palm oil extract (tocomin) on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin and α-tocopherol were more effective in the isolated aorta. Tocomin and α-tocopherol restored endothelial function in the presence of oxidant stress but α-, δ-, and γ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without, α-tocopherol. Tocotrienol rich tocomin is more effective than α-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and although α-, δ-, and γ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function. Saher F. Ali and Owen L. Woodman Copyright © 2015 Saher F. Ali and Owen L. Woodman. All rights reserved. Hydrogen Sulfide Signaling in Oxidative Stress and Aging Development Sun, 17 May 2015 07:13:38 +0000 http://www.hindawi.com/journals/omcl/2015/357824/ Guangdong Yang, Steven S. An, Yong Ji, Weihua Zhang, and Yanxi Pei Copyright © 2015 Guangdong Yang et al. All rights reserved. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells Thu, 14 May 2015 16:34:24 +0000 http://www.hindawi.com/journals/omcl/2015/741612/ Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM) for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose) polymer production. Significant decreases in total NAD(H) and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM) decreased levels of NAD(H) in primary human astrocytes. NAD(H) depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H)]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene. Jade Guest, Gilles J. Guillemin, Benjamin Heng, and Ross Grant Copyright © 2015 Jade Guest et al. All rights reserved. Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment Thu, 14 May 2015 14:20:22 +0000 http://www.hindawi.com/journals/omcl/2015/151972/ The clinical application of doxorubicin (DOX) is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D) is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF1), as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment. Qian Guo, Jiabin Guo, Rong Yang, Hui Peng, Jun Zhao, Li Li, and Shuangqing Peng Copyright © 2015 Qian Guo et al. All rights reserved. Optimisation of an Advanced Oxidation Protein Products Assay: Its Application to Studies of Oxidative Stress in Diabetes Mellitus Thu, 14 May 2015 13:48:21 +0000 http://www.hindawi.com/journals/omcl/2015/496271/ Advanced oxidation protein products (AOPP) are reportedly elevated in the plasma of patients with a number of diseases, including diabetes mellitus, that involve oxidative stress. However, the accurate measurement of AOPP in human plasma is hampered by the formation of a precipitate following the addition of potassium iodide and glacial acetic acid according to the published assay procedure. Here we describe a modification of the AOPP assay which eliminates interference by precipitation and provides a robust, reliable, and reproducible protocol for the measurement of iodide oxidising capacity in plasma samples (intra-assay CV 1.7–5.3%, interassay CV 5.3–10.5%). The improved method revealed a significant association of AOPP levels with age () and hypertension () in EDTA-anticoagulated plasma samples from 52 patients with diabetes and 38 nondiabetic control subjects, suggesting a possible link between plasma oxidising capacity and endothelial and/or vascular dysfunction. There was no significant difference between AOPP concentrations in diabetic (74.8 ± 7.2 M chloramine T equivalents) and nondiabetic (75.5 ± 7.0 M chloramine T equivalents) individuals. Emma L. Taylor, Kenneth R. Armstrong, David Perrett, Andrew T. Hattersley, and Paul G. Winyard Copyright © 2015 Emma L. Taylor et al. All rights reserved. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas Thu, 14 May 2015 11:48:07 +0000 http://www.hindawi.com/journals/omcl/2015/809492/ The aim of this study was to evaluate the effect of caloric restriction on the immune and hormonal responses during exercise in judo athletes. In a randomised order, 11 male judokas (age: 20.45 ± 0.51; height: 1.71 ± 0.3 m; and body weight: 75.9 ± 3.1 kg) participate in this study during a period of weight maintenance (baseline) and after 7 days of caloric restriction (CR). All subjects performed the Special Judo Fitness Test (SJFT) during the two conditions. Values for nutrient intakes were obtained from a 7 d food record kept during a period of weight maintenance and after a 7-day food restriction (−5~6 MJ/day). Our results showed that CR resulted in significant decreases in body weight () and performance (). However, heart rate and SJFT index () increase significantly during CR in comparison to baseline. Moreover, exercise leads to a significant increase in testosterone, cortisol, growth hormone (GH), leukocytes, neutrophils, TNF-α, and IL-6, in both CR and baseline conditions. Compared to baseline, TNF-α and IL-6 were significantly higher during CR condition (). Additionally, CR leads to an increase in cortisol and GH () and a decrease in testosterone concentrations (). Salma Abedelmalek, Hamdi Chtourou, Nizar Souissi, and Zouhair Tabka Copyright © 2015 Salma Abedelmalek et al. All rights reserved. TrkB-Mediated Neuroprotective and Antihypoxic Properties of Brain-Derived Neurotrophic Factor Wed, 13 May 2015 14:07:07 +0000 http://www.hindawi.com/journals/omcl/2015/453901/ The neuroprotective and antihypoxic effects of brain-derived neurotrophic factor (BDNF) on dissociated hippocampal cultures in a hypoxia model were investigated. These experiments demonstrate that 10 minutes of normobaric hypoxia increased the number of dead cells in primary culture, whereas a preventive application of BDNF increased the number of viable cells. Spontaneous bioelectrical and calcium activity in neural networks was analyzed using multielectrode arrays and functional intravital calcium imaging. The results indicate that BDNF affects the functional parameters of neuronal networks in dissociated hippocampal cultures over the 7-day posthypoxic period. In addition, the effects of k252a, an antagonist of tropomyosin-related kinase B (TrkB), on functional bioelectrical activity during and after acute hypoxia were investigated. It was shown that the protective effects of BDNF are associated with binding to the TrkB receptor. Finally, intravital fluorescent mRNA probes were used to study the role of NF-κB1 in the protective effects of BDNF. Our experiments revealed that BDNF application stimulates NF-κB1 mRNA synthesis in primary dissociated hippocampal cells under normal conditions but not in hypoxic state. Maria V. Vedunova, Tatiana A. Mishchenko, Elena V. Mitroshina, and Irina V. Mukhina Copyright © 2015 Maria V. Vedunova et al. All rights reserved. New Insights for Oxidative Stress and Diabetes Mellitus Tue, 12 May 2015 12:45:02 +0000 http://www.hindawi.com/journals/omcl/2015/875961/ The release of reactive oxygen species (ROS) and the generation of oxidative stress are considered critical factors for the pathogenesis of diabetes mellitus (DM), a disorder that is growing in prevalence and results in significant economic loss. New therapeutic directions that address the detrimental effects of oxidative stress may be especially warranted to develop effective care for the millions of individuals that currently suffer from DM. The mechanistic target of rapamycin (mTOR), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), and Wnt1 inducible signaling pathway protein 1 (WISP1) are especially justified to be considered treatment targets for DM since these pathways can address the complex relationship between stem cells, trophic factors, impaired glucose tolerance, programmed cell death pathways of apoptosis and autophagy, tissue remodeling, cellular energy homeostasis, and vascular biology that greatly impact the biology and disease progression of DM. The translation and development of these pathways into viable therapies will require detailed understanding of their proliferative nature to maximize clinical efficacy and limit adverse effects that have the potential to lead to unintended consequences. Kenneth Maiese Copyright © 2015 Kenneth Maiese. All rights reserved. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice Tue, 12 May 2015 10:01:04 +0000 http://www.hindawi.com/journals/omcl/2015/872428/ The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. Joo Wan Kim, Sae-Kwang Ku, Ki Young Kim, Sung Goo Kim, Min Ho Han, Gi-Young Kim, Hye Jin Hwang, Byung Woo Kim, Cheol Min Kim, and Yung Hyun Choi Copyright © 2015 Joo Wan Kim et al. All rights reserved. Role of Hydrogen Sulfide in Ischemia-Reperfusion Injury Tue, 12 May 2015 06:52:55 +0000 http://www.hindawi.com/journals/omcl/2015/186908/ Ischemia-reperfusion (I/R) injury is one of the major causes of high morbidity, disability, and mortality in the world. I/R injury remains a complicated and unresolved situation in clinical practice, especially in the field of solid organ transplantation. Hydrogen sulfide (H2S) is the third gaseous signaling molecule and plays a broad range of physiological and pathophysiological roles in mammals. H2S could protect against I/R injury in many organs and tissues, such as heart, liver, kidney, brain, intestine, stomach, hind-limb, lung, and retina. The goal of this review is to highlight recent findings regarding the role of H2S in I/R injury. In this review, we present the production and metabolism of H2S and further discuss the effect and mechanism of H2S in I/R injury. Dongdong Wu, Jun Wang, Hui Li, Mengzhou Xue, Ailing Ji, and Yanzhang Li Copyright © 2015 Dongdong Wu et al. All rights reserved. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders Mon, 11 May 2015 13:22:18 +0000 http://www.hindawi.com/journals/omcl/2015/940131/ Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer’s disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging. Mariarita Romanucci and Leonardo Della Salda Copyright © 2015 Mariarita Romanucci and Leonardo Della Salda. All rights reserved. Hydrogen Sulfide Alleviates Cadmium-Induced Cell Death through Restraining ROS Accumulation in Roots of Brassica rapa L. ssp. pekinensis Mon, 11 May 2015 11:06:51 +0000 http://www.hindawi.com/journals/omcl/2015/804603/ Hydrogen sulfide (H2S) is a cell signal molecule produced endogenously and involved in regulation of tolerance to biotic and abiotic stress in plants. In this work, we used molecular biology, physiology, and histochemical methods to investigate the effects of H2S on cadmium- (Cd-) induced cell death in Chinese cabbage roots. Cd stress stimulated a rapid increase of endogenous H2S in roots. Additionally, root length was closely related to the cell death rate. Pretreatment with sodium hydrosulfide (NaHS), a H2S donor, alleviated the growth inhibition caused by Cd in roots—this effect was more pronounced at 5 μM NaHS. Cd-induced cell death in roots was significantly reduced by 5 μM NaHS treatment. Under Cd stress, activities of the antioxidant enzymes were significantly enhanced in roots. NaHS + Cd treatment made their activities increase further compared with Cd exposure alone. Enhanced antioxidant enzyme activity led to a decline in reactive oxygen species accumulation and lipid peroxidation. In contrast, these effects were reversed by hydroxylamine, a H2S inhibitor. These results suggested that H2S alleviated the cell death caused by Cd via upregulation of antioxidant enzyme activities to remove excessive reactive oxygen species and reduce cell oxidative damage. Liping Zhang, Yanxi Pei, Hongjiao Wang, Zhuping Jin, Zhiqiang Liu, Zengjie Qiao, Huihui Fang, and Yanjie Zhang Copyright © 2015 Liping Zhang et al. All rights reserved. The Cardioprotective Effects of Hydrogen Sulfide in Heart Diseases: From Molecular Mechanisms to Therapeutic Potential Mon, 11 May 2015 10:37:28 +0000 http://www.hindawi.com/journals/omcl/2015/925167/ Hydrogen sulfide (H2S) is now recognized as a third gaseous mediator along with nitric oxide (NO) and carbon monoxide (CO), though it was originally considered as a malodorous and toxic gas. H2S is produced endogenously from cysteine by three enzymes in mammalian tissues. An increasing body of evidence suggests the involvement of H2S in different physiological and pathological processes. Recent studies have shown that H2S has the potential to protect the heart against myocardial infarction, arrhythmia, hypertrophy, fibrosis, ischemia-reperfusion injury, and heart failure. Some mechanisms, such as antioxidative action, preservation of mitochondrial function, reduction of apoptosis, anti-inflammatory responses, angiogenic actions, regulation of ion channel, and interaction with NO, could be responsible for the cardioprotective effect of H2S. Although several mechanisms have been identified, there is a need for further research to identify the specific molecular mechanism of cardioprotection in different cardiac diseases. Therefore, insight into the molecular mechanisms underlying H2S action in the heart may promote the understanding of pathophysiology of cardiac diseases and lead to new therapeutic targets based on modulation of H2S production. Yaqi Shen, Zhuqing Shen, Shanshan Luo, Wei Guo, and Yi Zhun Zhu Copyright © 2015 Yaqi Shen et al. All rights reserved. The Hydrogen Sulfide Donor NaHS Delays Programmed Cell Death in Barley Aleurone Layers by Acting as an Antioxidant Mon, 11 May 2015 10:02:32 +0000 http://www.hindawi.com/journals/omcl/2015/714756/ H2S is a signaling molecule in plants and animals. Here we investigated the effects of H2S on programmed cell death (PCD) in barley (Hordeum vulgare L.) aleurone layers. The H2S donor NaHS significantly delayed PCD in aleurone layers isolated from imbibed embryoless barley grain. NaHS at 0.25 mM effectively reduced the accumulation of superoxide anion (), hydrogen peroxide (H2O2), and malondialdehyde (MDA), promoted the activity of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and decreased those of lipoxygenase (LOX) in isolated aleurone layers. Quantitative-PCR showed that NaHS treatment of aleurone tissue led to enhanced transcript levels of the antioxidant genes HvSOD1, HvAPX, HvCAT1, and HvCAT2 and repressed transcript levels of HvLOX (lipoxygenase gene) and of two cysteine protease genes HvEPA and HvCP3-31. NaHS treatment in gibberellic acid- (GA-) treated aleurone layers also delayed the PCD process, reduced the content of , and increased POD activity while decreasing LOX activity. Furthermore, α-amylase secretion in barley aleurone layers was enhanced by NaHS treatment regardless of the presence or absence of GA. These data imply that H2S acted as an antioxidant in delaying PCD and enhances α-amylase secretion regardless of the presence of GA in barley aleurone layers. Ying-Xin Zhang, Kang-Di Hu, Kai Lv, Yan-Hong Li, Lan-Ying Hu, Xi-Qi Zhang, Long Ruan, Yong-Sheng Liu, and Hua Zhang Copyright © 2015 Ying-Xin Zhang et al. All rights reserved. Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt Mon, 11 May 2015 09:56:56 +0000 http://www.hindawi.com/journals/omcl/2015/754670/ Background. The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC) apoptosis. Methods. Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE), cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc). Fluorescent probes were used to quantitatively detect superoxide anion generation and measure the in situ superoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL) methods. Results. High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt. Conclusion. H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury. Yanfang Zong, Yaqian Huang, Siyao Chen, Mingzhu Zhu, Qinghua Chen, Shasha Feng, Yan Sun, Qingyou Zhang, Chaoshu Tang, Junbao Du, and Hongfang Jin Copyright © 2015 Yanfang Zong et al. All rights reserved. Hydrogen Sulfide: A Therapeutic Candidate for Fibrotic Disease? Mon, 11 May 2015 09:25:58 +0000 http://www.hindawi.com/journals/omcl/2015/458720/ Fibrotic diseases including chronic kidney disease, liver cirrhosis, idiopathic pulmonary fibrosis, and chronic disease account for 45% mortality in the developed countries and pose a great threat to the global health. Many great targets and molecules have been reported to be involved in the initiation and/or progression of fibrosis, among which inflammation and oxidative stress are well-recognized modulation targets. Hydrogen sulfide (H2S) is the third gasotransmitter with potent properties in inhibiting inflammation and oxidative stress in various organs. Recent evidence suggests that plasma H2S level is decreased in various animal models of fibrotic diseases and supplement of exogenous H2S is able to ameliorate fibrosis in the kidney, lung, liver, and heart. This leads us to propose that modulation of H2S production may represent a promising therapeutic venue for the treatment of a variety of fibrotic diseases. Here, we summarize and discuss the current data on the role and underlying mechanisms of H2S in fibrosis diseases related to heart, liver, kidney, and other organs. Kai Song, Qian Li, Xiao-Ya Yin, Ying Lu, Chun-Feng Liu, and Li-Fang Hu Copyright © 2015 Kai Song et al. All rights reserved. Sulfur Dioxide Enhances Endogenous Hydrogen Sulfide Accumulation and Alleviates Oxidative Stress Induced by Aluminum Stress in Germinating Wheat Seeds Mon, 11 May 2015 09:23:30 +0000 http://www.hindawi.com/journals/omcl/2015/612363/ Aluminum ions are especially toxic to plants in acidic soils. Here we present evidences that SO2 protects germinating wheat grains against aluminum stress. SO2 donor (NaHSO3/Na2SO3) pretreatment at 1.2 mM reduced the accumulation of superoxide anion, hydrogen peroxide, and malondialdehyde, enhanced the activities of guaiacol peroxidase, catalase, and ascorbate peroxidase, and decreased the activity of lipoxygenase in germinating wheat grains exposed to Al stress. We also observed higher accumulation of hydrogen sulfide (H2S) in SO2-pretreated grain, suggesting the tight relation between sulfite and sulfide. Wheat grains geminated in water for 36 h were pretreated with or without 1 mM SO2 donor for 12 h prior to exposure to Al stress for 48 h and the ameliorating effects of SO2 on wheat radicles were studied. SO2 donor pretreatment reduced the content of reactive oxygen species, protected membrane integrity, and reduced Al accumulation in wheat radicles. Gene expression analysis showed that SO2 donor pretreatment decreased the expression of Al-responsive genes TaWali1, TaWali2, TaWali3, TaWali5, TaWali6, and TaALMT1 in radicles exposed to Al stress. These results suggested that SO2 could increase endogenous H2S accumulation and the antioxidant capability and decrease endogenous Al content in wheat grains to alleviate Al stress. Dong-Bo Zhu, Kang-Di Hu, Xi-Kai Guo, Yong Liu, Lan-Ying Hu, Yan-Hong Li, Song-Hua Wang, and Hua Zhang Copyright © 2015 Dong-Bo Zhu et al. All rights reserved. Rimonabant Improves Oxidative/Nitrosative Stress in Mice with Nonalcoholic Fatty Liver Disease Mon, 11 May 2015 09:03:33 +0000 http://www.hindawi.com/journals/omcl/2015/842108/ The present study deals with the effects of rimonabant on oxidative/nitrosative stress in high diet- (HFD-) induced experimental nonalcoholic fatty liver disease (NAFLD). Male mice C57BL/6 were divided into the following groups: control group fed with control diet for 20 weeks (C; ); group fed with HFD for 20 weeks (HF; ); group fed with standard diet and treated with rimonabant after 18 weeks (R; ); group fed with HFD and treated with rimonabant after 18 weeks (HFR; ). Daily dose of rimonabant (10 mg/kg) was administered to HFR and R group by oral gavage for two weeks. Treatment induced a decrease in hepatic malondialdehyde concentration in HFR group compared to HF group . The concentration of nitrites + nitrates in liver was decreased in HFR group compared to HF group . Liver content of reduced glutathione was higher in HFR group compared to HF group . Total liver superoxide dismutase activity in HFR group was decreased in comparison with HF group . It was found that rimonabant may influence hepatic iron, zinc, copper, and manganese status. Our study indicates potential usefulness of cannabinoid receptor type 1 blockade in the treatment of HFD-induced NAFLD. Bojan Jorgačević, Dušan Mladenović, Milica Ninković, Milena Vesković, Vesna Dragutinović, Aleksandar Vatazević, Danijela Vučević, Rada Ješić Vukićević, and Tatjana Radosavljević Copyright © 2015 Bojan Jorgačević et al. All rights reserved.