Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship Tue, 31 Mar 2015 12:41:35 +0000 http://www.hindawi.com/journals/omcl/2015/370312/ Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI. Cristina Angeloni, Cecilia Prata, Francesco Vieceli Dalla Sega, Roberto Piperno, and Silvana Hrelia Copyright © 2015 Cristina Angeloni et al. All rights reserved. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension Tue, 31 Mar 2015 10:34:43 +0000 http://www.hindawi.com/journals/omcl/2015/535686/ We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. Magdalena Cristóbal-García, Fernando E. García-Arroyo, Edilia Tapia, Horacio Osorio, Abraham S. Arellano-Buendía, Magdalena Madero, Bernardo Rodríguez-Iturbe, José Pedraza-Chaverrí, Francisco Correa, Cecilia Zazueta, Richard J. Johnson, and Laura-Gabriela Sánchez Lozada Copyright © 2015 Magdalena Cristóbal-García et al. All rights reserved. The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease Mon, 30 Mar 2015 13:26:48 +0000 http://www.hindawi.com/journals/omcl/2015/234104/ Mitochondrial dysfunction is a hallmark of multiple cardiovascular disorders, including ischemic heart disease. Although mitochondria are well recognized for their role in energy production and cell death, mechanisms by which they control excitation-contraction coupling, excitability, and arrhythmias are less clear. The translocator protein (TSPO) is an outer mitochondrial membrane protein that is expressed in multiple organ systems. The abundant expression of TSPO in macrophages has been leveraged to image the immune response of the heart to inflammatory processes. More recently, the recognition of TSPO as a regulator of energy-dissipating mitochondrial pathways has extended its utility from a diagnostic marker of inflammation to a therapeutic target influencing diverse pathophysiological processes. Here, we provide an overview of the emerging role of TSPO in ischemic heart disease. We highlight the importance of TSPO in the regenerative process of reactive oxygen species (ROS) induced ROS release through its effects on the inner membrane anion channel (IMAC) and the permeability transition pore (PTP). We discuss evidence implicating TSPO in arrhythmogenesis in the settings of acute ischemia-reperfusion injury and myocardial infarction. Lukas J. Motloch, Jun Hu, and Fadi G. Akar Copyright © 2015 Lukas J. Motloch et al. All rights reserved. Oxidative Stress Responses and NRF2 in Human Leukaemia Mon, 30 Mar 2015 12:03:17 +0000 http://www.hindawi.com/journals/omcl/2015/454659/ Oxidative stress as a result of elevated levels of reactive oxygen species (ROS) has been observed in almost all cancers, including leukaemia, where they contribute to disease development and progression. However, cancer cells also express increased levels of antioxidant proteins which detoxify ROS. This includes glutathione, the major antioxidant in human cells, which has recently been identified to have dysregulated metabolism in human leukaemia. This suggests that critical balance of intracellular ROS levels is required for cancer cell function, growth, and survival. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor plays a dual role in cancer. Primarily, NRF2 is a transcription factor functioning to protect nonmalignant cells from malignant transformation and oxidative stress through transcriptional activation of detoxifying and antioxidant enzymes. However, once malignant transformation has occurred within a cell, NRF2 functions to protect the tumour from oxidative stress and chemotherapy-induced cytotoxicity. Moreover, inhibition of the NRF2 oxidative stress pathway in leukaemia cells renders them more sensitive to cytotoxic chemotherapy. Our improved understanding of NRF2 biology in human leukaemia may permit mechanisms by which we could potentially improve future cancer therapies. This review highlights the mechanisms by which leukaemic cells exploit the NRF2/ROS response to promote their growth and survival. Amina Abdul-Aziz, David J. MacEwan, Kristian M. Bowles, and Stuart A. Rushworth Copyright © 2015 Amina Abdul-Aziz et al. All rights reserved. In Vitro Toxicity of Epigallocatechin Gallate in Rat Liver Mitochondria and Hepatocytes Mon, 30 Mar 2015 10:11:22 +0000 http://www.hindawi.com/journals/omcl/2015/476180/ Epigallocatechin-3-gallate (EGCG) is the main compound of green tea with well-described antioxidant, anti-inflammatory, and tumor-suppressing properties. However, EGCG at high doses was reported to cause liver injury. In this study, we evaluated the effect of EGCG on primary culture of rat hepatocytes and on rat liver mitochondria in permeabilized hepatocytes. The 24-hour incubation with EGCG in concentrations of 10 μmol/L and higher led to signs of cellular injury and to a decrease in hepatocyte functions. The effect of EGCG on the formation of reactive oxygen species (ROS) was biphasic. While low doses of EGCG decreased ROS production, the highest tested dose induced a significant increase in ROS formation. Furthermore, we observed a decline in mitochondrial membrane potential in cells exposed to EGCG when compared to control cells. In permeabilized hepatocytes, EGCG caused damage of the outer mitochondrial membrane and an uncoupling of oxidative phosphorylation. EGCG in concentrations lower than 10 μmol/L was recognized as safe for hepatocytes in vitro. Otto Kucera, Vojtech Mezera, Alena Moravcova, Rene Endlicher, Halka Lotkova, Zdenek Drahota, and Zuzana Cervinkova Copyright © 2015 Otto Kucera et al. All rights reserved. Analysis of Chemokines and Receptors Expression Profile in the Myelin Mutant Taiep Rat Wed, 25 Mar 2015 12:28:09 +0000 http://www.hindawi.com/journals/omcl/2015/397310/ Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT2 Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat. Guadalupe Soto-Rodriguez, Juan-Antonio Gonzalez-Barrios, Daniel Martinez-Fong, Victor-Manuel Blanco-Alvarez, Jose R. Eguibar, Araceli Ugarte, Francisco Martinez-Perez, Eduardo Brambila, Lourdes Millán-Perez Peña, Nidia-Gary Pazos-Salazar, Maricela Torres-Soto, Guadalupe Garcia-Robles, Constantino Tomas-Sanchez, and Bertha Alicia Leon-Chavez Copyright © 2015 Guadalupe Soto-Rodriguez et al. All rights reserved. Effects of Polyphenols from Grape Seeds on Renal Lithiasis Wed, 25 Mar 2015 08:48:33 +0000 http://www.hindawi.com/journals/omcl/2015/813737/ Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity. Felix Grases, Rafel M. Prieto, Rafel A. Fernandez-Cabot, Antonia Costa-Bauzá, Fernando Tur, and Jose Juan Torres Copyright © 2015 Felix Grases et al. All rights reserved. Oxidant Antioxidants and Adaptive Responses to Exercise Tue, 24 Mar 2015 12:39:42 +0000 http://www.hindawi.com/journals/omcl/2015/290190/ Paola Venditti, Mari Carmen Gomez-Cabrera, Yong Zhang, and Zsolt Radak Copyright © 2015 Paola Venditti et al. All rights reserved. Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms Tue, 24 Mar 2015 10:00:06 +0000 http://www.hindawi.com/journals/omcl/2015/230182/ The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. Elena Gammella, Stefania Recalcati, Ilona Rybinska, Paolo Buratti, and Gaetano Cairo Copyright © 2015 Elena Gammella et al. All rights reserved. Corrigendum to “Reduced Oxidative Stress Contributes to the Lipid Lowering Effects of Isoquercitrin in Free Fatty Acids Induced Hepatocytes” Mon, 23 Mar 2015 13:21:23 +0000 http://www.hindawi.com/journals/omcl/2015/383525/ Waseem Hassan, Gao Rongyin, Abdelkader Daoud, Lin Ding, Lulu Wang, Jun Liu, and Jing Shang Copyright © 2015 Waseem Hassan et al. All rights reserved. Oxidative Stress and Adipocyte Biology: Focus on the Role of AGEs Mon, 23 Mar 2015 08:24:04 +0000 http://www.hindawi.com/journals/omcl/2015/534873/ Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression. Florence Boyer, Jennifer Baraka Vidot, Alexis Guerin Dubourg, Philippe Rondeau, M. Faadiel Essop, and Emmanuel Bourdon Copyright © 2015 Florence Boyer et al. All rights reserved. 3-(3-Pyridylmethylidene)-2-indolinone Reduces the Severity of Colonic Injury in a Murine Model of Experimental Colitis Sun, 22 Mar 2015 13:41:28 +0000 http://www.hindawi.com/journals/omcl/2015/959253/ Nrf2 is the key transcription factor regulating the antioxidant response which is crucial for cytoprotection against extracellular stresses. Numerous in vivo studies indicate that Nrf2 plays a protective role in anti-inflammatory response. 3-(3-Pyridylmethylidene)-2-indolinone (PMID) is a synthesized derivative of 2-indolinone compounds. Our previous study suggested that PMID induces the activation of Nrf2/ARE pathway, then protecting against oxidative stress-mediated cell death. However, little is known regarding the anti-inflammatory properties of PMID in severe inflammatory phenotypes. In the present study we determined if PMID treatment protects mice from dextran sodium sulphate- (DSS-) induced colitis. The result suggests that treatment with PMID prior to colitis induction significantly reduced body weight loss, shortened colon length, and decreased disease activity index compared to control mice. Histopathological analysis of the colon revealed attenuated inflammation in PMID pretreated animals. The levels of inflammatory markers in colon tissue and serum were reduced associated with inhibition of NF-κB activation. The expression levels of Nrf2-dependent genes such as HO-1, NQO1, and Nrf2 were increased in PMID pretreated mice. However, PMID pretreatment did not prevent DSS-induced colitis in Nrf2 knockout mice. These data indicate that PMID pretreatment in mice confers protection against DSS-induced colitis in Nrf2-dependent manner, suggesting a potential role of PMID in anti-inflammatory response. Kun-Ping Wang, Chao Zhang, Shou-Guo Zhang, En-Dong Liu, Lan Dong, Xiang-Zhen Kong, Peng Cao, Chun-Ping Hu, Ke Zhao, Yi-Qun Zhan, Xiao-Ming Dong, Chang-Hui Ge, Miao Yu, Hui Chen, Lin Wang, Xiao-Ming Yang, and Chang-Yan Li Copyright © 2015 Kun-Ping Wang et al. All rights reserved. Cardioprotective Effects of Voluntary Exercise in a Rat Model: Role of Matrix Metalloproteinase-2 Sun, 22 Mar 2015 11:07:58 +0000 http://www.hindawi.com/journals/omcl/2015/876805/ Background. Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs) play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury. Methods. Male Wistar rats were divided into control and exercising groups. After a 6-week period, the serum level of MMP-2, basal blood pressure, cardiac angina susceptibility (the ST segment depression provoked by epinephrine and 30 s later phentolamine), AVP-induced heart perfusion and aorta ring contraction, infarct size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP-2 activity were measured. Results. Voluntary wheel-running exercise decreased both the sera (64 kDa and 72 kDa) and the coronary effluent (64 kDa) MMP-2 level, reduced the development of ST depression, improved the isolated heart perfusion, and decreased the ratio of infarct size. Conclusion. 6 weeks of voluntary exercise training preserved the heart against cardiac injury. This protective mechanism might be associated with the decreased activity of MMP-2. Anikó Pósa, Renáta Szabó, Krisztina Kupai, Zoltán Baráth, Zita Szalai, Anett Csonka, Médea Veszelka, Mariann Gyöngyösi, Zsolt Radák, Rudolf Ménesi, Imre Pávó, Anikó Magyariné Berkó, and Csaba Varga Copyright © 2015 Anikó Pósa et al. All rights reserved. Training Effects on ROS Production Determined by Electron Paramagnetic Resonance in Master Swimmers Sun, 22 Mar 2015 09:23:18 +0000 http://www.hindawi.com/journals/omcl/2015/804794/ Acute exercise induces an increase in Reactive Oxygen Species (ROS) production dependent on exercise intensity with highest ROS amount generated by strenuous exercise. However, chronic repetition of exercise, that is, exercise training, may reduce exercise-induced oxidative stress. Aim of this study was to evaluate the effects of 6-weeks high-intensity discontinuous training (HIDT), characterized by repeated variations of intensity and changes of redox potential, on ROS production and antioxidant capacity in sixteen master swimmers. Time course changes of ROS generation were assessed by Electron Paramagnetic Resonance in capillary blood by a microinvasive approach. An incremental arm-ergometer exercise (IE) until exhaustion was carried out at both before (PRE) and after (POST) training (Trg) period. A significant () increase of ROS production from REST to the END of IE in PRE Trg ( versus  µmol·min−1) was observed. HIDT increased peak oxygen consumption ( versus  mL·kg−1·min−1 PRE and POST Trg, resp.) and the antioxidant capacity (+13%) while it significantly decreased the ROS production both at REST (−20%) and after IE (−25%). The observed link between ROS production, adaptive antioxidant defense mechanisms, and peak oxygen consumption provides new insight into the correlation between ROS response pathways and muscle metabolic function. Simona Mrakic-Sposta, Maristella Gussoni, Simone Porcelli, Lorenzo Pugliese, Gaspare Pavei, Giuseppe Bellistri, Michela Montorsi, Philippe Tacchini, and Alessandra Vezzoli Copyright © 2015 Simona Mrakic-Sposta et al. All rights reserved. Acute Exercise Induced Mitochondrial H2O2 Production in Mouse Skeletal Muscle: Association with p66Shc and FOXO3a Signaling and Antioxidant Enzymes Sun, 22 Mar 2015 09:12:24 +0000 http://www.hindawi.com/journals/omcl/2015/536456/ Exercise induced skeletal muscle phenotype change involves a complex interplay between signaling pathways and downstream regulators. This study aims to investigate the effect of acute exercise on mitochondrial H2O2 production and its association with , FOXO3a, and antioxidant enzymes. Male ICR/CD-1 mice were subjected to an acute exercise. Muscle tissues (gastrocnemius and quadriceps femoris) were taken after exercise to measure mitochondrial H2O2 content, expression of and FOXO3a, and the activity of antioxidant enzymes. The results showed that acute exercise significantly increased mitochondrial H2O2 content and expressions of and FOXO3a in a time-dependent manner, with a linear correlation between the increase in H2O2 content and or FOXO3a expression. The activity of mitochondrial catalase was slightly reduced in the 90 min exercise group, but it was significantly higher in groups with 120 and 150 min exercise compared to that of 90 min exercise group. The activity of SOD was not significantly affected. The results indicate that acute exercise increases mitochondrial H2O2 production in the skeletal muscle, which is associated with the upregulation of and FOXO3a. The association of and FOXO3a signaling with exercise induced H2O2 generation may play a role in regulating cellular oxidative stress during acute exercise. Ping Wang, Chun Guang Li, Zhengtang Qi, Di Cui, and Shuzhe Ding Copyright © 2015 Ping Wang et al. All rights reserved. Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues Sun, 22 Mar 2015 09:09:08 +0000 http://www.hindawi.com/journals/omcl/2015/732090/ We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. Simona Carfagna, Gaetana Napolitano, Daniela Barone, Gabriele Pinto, Antonino Pollio, and Paola Venditti Copyright © 2015 Simona Carfagna et al. All rights reserved. Assessment of Eccentric Exercise-Induced Oxidative Stress Using Oxidation-Reduction Potential Markers Sun, 22 Mar 2015 09:00:50 +0000 http://www.hindawi.com/journals/omcl/2015/204615/ The aim of the present study was to investigate the use of static (sORP) and capacity ORP (cORP) oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72 h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress. Dimitrios Stagos, Nikolaos Goutzourelas, Amalia-Maria Ntontou, Ioannis Kafantaris, Chariklia K. Deli, Athanasios Poulios, Athanasios Z. Jamurtas, David Bar-Or, and Dimitrios Kouretas Copyright © 2015 Dimitrios Stagos et al. All rights reserved. Exercise Training and Calorie Restriction Influence the Metabolic Parameters in Ovariectomized Female Rats Thu, 19 Mar 2015 14:19:09 +0000 http://www.hindawi.com/journals/omcl/2015/787063/ The estrogen deficiency after menopause leads to overweight or obesity, and physical exercise is one of the important modulators of this body weight gain. Female Wistar rats underwent ovariectomy surgery (OVX) or sham operation (SO). OVX and SO groups were randomized into new groups based on the voluntary physical activity (with or without running) and the type of diet for 12 weeks. Rats were fed standard chow (CTRL), high triglyceride diet (HT), or restricted diet (CR). The metabolic syndrome was assessed by measuring the body weight gain, the glucose sensitivity, and the levels of insulin, triglyceride, leptin, and aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT). The exercise training combined with the CR resulted in improvements in the glucose tolerance and the insulin sensitivity. Plasma TG, AST, and ALT levels were significantly higher in OVX rats fed with HT but these high values were suppressed by exercise and CR. Compared to SO animals, estrogen deprivation with HT caused a significant increase in leptin level. Our data provide evidence that CR combined with voluntary physical exercise can be a very effective strategy to prevent the development of a metabolic syndrome induced by high calorie diet. Anikó Pósa, Renáta Szabó, Krisztina Kupai, Anett Csonka, Zita Szalai, Médea Veszelka, Szilvia Török, Lejla Daruka, and Csaba Varga Copyright © 2015 Anikó Pósa et al. All rights reserved. Relationship between Inflammation and Oxidative Stress and Cognitive Decline in the Institutionalized Elderly Thu, 19 Mar 2015 11:57:57 +0000 http://www.hindawi.com/journals/omcl/2015/804198/ Objective. Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions. Methods. The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated. Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy. Marília Baierle, Sabrina N. Nascimento, Angela M. Moro, Natália Brucker, Fernando Freitas, Bruna Gauer, Juliano Durgante, Suelen Bordignon, Murilo Zibetti, Clarissa M. Trentini, Marta M. M. F. Duarte, Tilman Grune, Nicolle Breusing, and Solange C. Garcia Copyright © 2015 Marília Baierle et al. All rights reserved. The Role of Oxidative Stress and Autophagy in Atherosclerosis Wed, 18 Mar 2015 11:55:33 +0000 http://www.hindawi.com/journals/omcl/2015/130315/ Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease. Ida Perrotta and Saveria Aquila Copyright © 2015 Ida Perrotta and Saveria Aquila. All rights reserved. Changes in the Conformational State of Hemoglobin in Hemodialysed Patients with Chronic Renal Failure Wed, 18 Mar 2015 06:53:43 +0000 http://www.hindawi.com/journals/omcl/2015/783073/ The aim of this study was to evaluate the properties of internal components of erythrocytes in chronic renal failure (CRF) patients undergoing hemodialysis (HD) in comparison to control subjects. For investigation of conformational state of hemoglobin and nonheme proteins (NHP) the maleimide spin label (MSL) in electron paramagnetic resonance (EPR) was applied. The studies were performed using MSL in whole cells and hemolysate as well as proteins separated by ion exchange chromatography and checked by electrophoresis. Additionally the level of –SH groups in hemolysate and isolated internal proteins of CRF erythrocytes was determined using 4,4′-dithiodipyridine. All measurements were performed before and after hemodialysis. Oxidative stress accompanying CRF/hemodialysed patients caused a significant decrease in the mobility of internal components inside erythrocytes indicated by MSL (P < 0.02). The significant decrease in mobility of spin labeled HbA1c and HbA both before and after HD (P < 0.0002) as well as in nonheme proteins before hemodialysis (P < 0.05) versus control was indicated. Decrease in mobility of internal components of erythrocytes was accompanied by loss of thiols before and after hemodialysis versus control in NHP (P < 0.05), HbA1c (P < 0.0002), and HbA (P < 0.0005). These findings showed oxidative influence of hemodialysis on hemoglobins and internal nonheme proteins in erythrocytes of CRF patients. Anna Pieniazek and Krzysztof Gwozdzinski Copyright © 2015 Anna Pieniazek and Krzysztof Gwozdzinski. All rights reserved. Intracellular Oxidant Activity, Antioxidant Enzyme Defense System, and Cell Senescence in Fibroblasts with Trisomy 21 Tue, 17 Mar 2015 07:54:47 +0000 http://www.hindawi.com/journals/omcl/2015/509241/ Down’s syndrome (DS) is characterized by a complex phenotype associated with chronic oxidative stress and mitochondrial dysfunction. Overexpression of genes on chromosome-21 is thought to underlie the pathogenesis of the major phenotypic features of DS, such as premature aging. Using cultured fibroblasts with trisomy 21 (T21F), this study aimed to ascertain whether an imbalance exists in activities, mRNA, and protein expression of the antioxidant enzymes SOD1, SOD2, glutathione-peroxidase, and catalase during the cell replication process in vitro. T21F had high SOD1 expression and activity which led to an interenzymatic imbalance in the antioxidant defense system, accentuated with replicative senescence. Intracellular ROS production and oxidized protein levels were significantly higher in T21F compared with control cells; furthermore, a significant decline in intracellular ATP content was detected in T21F. Cell senescence was found to appear prematurely in DS cells as shown by SA-β-Gal assay and p21 assessment, though not apoptosis, as neither p53 nor the proapoptotic proteins cytochrome c and caspase 9 were altered in T21F. These novel findings would point to a deleterious role of oxidatively modified molecules in early cell senescence of T21F, thereby linking replicative and stress-induced senescence in cultured cells to premature aging in DS. Víctor Rodríguez-Sureda, Ángel Vilches, Olga Sánchez, Laura Audí, and Carmen Domínguez Copyright © 2015 Víctor Rodríguez-Sureda et al. All rights reserved. Saraca indica Bark Extract Shows In Vitro Antioxidant, Antibreast Cancer Activity and Does Not Exhibit Toxicological Effects Mon, 16 Mar 2015 10:10:08 +0000 http://www.hindawi.com/journals/omcl/2015/205360/ Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy. Navneet Kumar Yadav, Karan Singh Saini, Zakir Hossain, Ankur Omer, Chetan Sharma, Jiaur R. Gayen, Poonam Singh, K. R. Arya, and R. K. Singh Copyright © 2015 Navneet Kumar Yadav et al. All rights reserved. Chronic Kidney Disease Influences Multiple Systems: Describing the Relationship between Oxidative Stress, Inflammation, Kidney Damage, and Concomitant Disease Sun, 15 Mar 2015 06:27:02 +0000 http://www.hindawi.com/journals/omcl/2015/806358/ Chronic kidney disease (CKD) is characterized by increased levels of oxidative stress and inflammation. Oxidative stress and inflammation promote renal injury via damage to molecular components of the kidney. Unfortunately, relationships between inflammation and oxidative stress are cyclical in that the inflammatory processes that exist to repair radical-mediated damage may be a source of additional free radicals, resulting in further damage to renal tissue. Oxidative stress and inflammation also have the ability to become systemic, serving to injure tissues distal to the site of original insult. This review describes select mediators in the exacerbatory relationship between oxidative stress, inflammation, and CKD. This review also discusses oxidative stress, inflammation, and CKD as they pertain to the development and progression of common CKD-associated comorbidities. Lastly, the utility of several widely accessible and cost-effective lifestyle interventions and their ability to reduce oxidative stress and inflammation are discussed and recommendations for future research are provided. Patrick S. Tucker, Aaron T. Scanlan, and Vincent J. Dalbo Copyright © 2015 Patrick S. Tucker et al. All rights reserved. Oxidative Stress to the Cornea, Changes in Corneal Optical Properties, and Advances in Treatment of Corneal Oxidative Injuries Wed, 11 Mar 2015 10:43:15 +0000 http://www.hindawi.com/journals/omcl/2015/591530/ Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown. Cestmir Cejka and Jitka Cejkova Copyright © 2015 Cestmir Cejka and Jitka Cejkova. All rights reserved. Sca-1+ Cells from Fetal Heart with High Aldehyde Dehydrogenase Activity Exhibit Enhanced Gene Expression for Self-Renewal, Proliferation, and Survival Tue, 10 Mar 2015 14:21:41 +0000 http://www.hindawi.com/journals/omcl/2015/730683/ Stem/progenitor cells from multiple tissues have been isolated based on enhanced activity of cytosolic aldehyde dehydrogenase (ALDH) enzyme. ALDH activity has emerged as a reliable marker for stem/progenitor cells, such that cells from multiple tissues have been shown to possess enhanced stemness properties (self-renewal and multipotency). So far though, not much is known about ALDH activity in specific fetal organs. In this study, we sought to analyze the presence and activity of the ALDH enzyme in the stem cell antigen-1-positive (Sca-1+) cells of fetal human heart. Biochemical assays showed that a subpopulation of Sca-1+ cells (15%) possess significantly high ALDH1 activity. This subpopulation showed increased expression of self-renewal markers compared to the fraction. The fraction also exhibited significant increase in proliferation and pro-survival gene expression. In addition, only the and not the fraction could give rise to all the cell types of the original population, demonstrating multipotency. cells showed increased resistance against aldehyde challenge compared to cells. These results indicate that subpopulation of the cultured human fetal cells has enhanced self-renewal, multipotency, high proliferation, and survival, indicating that this might represent a primitive stem cell population within the fetal human heart. Devaveena Dey, Guodong Pan, Nadimpalli Ravi S. Varma, and Suresh Selvaraj Palaniyandi Copyright © 2015 Devaveena Dey et al. All rights reserved. Oxidative Stress and Immune System in Vitiligo and Thyroid Diseases Mon, 09 Mar 2015 11:10:57 +0000 http://www.hindawi.com/journals/omcl/2015/631927/ Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo. Roberta Colucci, Federica Dragoni, and Silvia Moretti Copyright © 2015 Roberta Colucci et al. All rights reserved. Dietary Nitrate Is a Modifier of Vascular Gene Expression in Old Male Mice Sun, 08 Mar 2015 12:58:31 +0000 http://www.hindawi.com/journals/omcl/2015/658264/ Aging leads to a number of disadvantageous changes in the cardiovascular system. Deterioration of vascular homoeostasis with increase in oxidative stress, chronic low-grade inflammation, and impaired nitric oxide bioavailability results in endothelial dysfunction, increased vascular stiffness, and compromised arterial-ventricular interactions. A chronic dietary supplementation with the micronutrient nitrate has been demonstrated to improve vascular function. Healthy dietary patterns may regulate gene expression profiles. However, the mechanisms are incompletely understood. The changes that occur at the gene expression level and transcriptional profile following a nutritional modification with nitrate have not been elucidated. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of old mice, which were treated with dietary nitrate. Our results highlight differentially expressed genes overrepresented in gene ontology categories. Molecular interaction and reaction pathways involved in the calcium-signaling pathway and the detoxification system were identified. Our results provide novel insight to an altered gene-expression profile in old mice following nitrate supplementation. This supports the general notion of nutritional approaches to modulate age-related changes of vascular functions and its detrimental consequences. Christos Rammos, Matthias Totzeck, René Deenen, Karl Köhrer, Malte Kelm, Tienush Rassaf, and Ulrike B. Hendgen-Cotta Copyright © 2015 Christos Rammos et al. All rights reserved. Potential Therapeutic Role of L-Carnitine in Skeletal Muscle Oxidative Stress and Atrophy Conditions Sun, 08 Mar 2015 09:49:21 +0000 http://www.hindawi.com/journals/omcl/2015/646171/ The targeting of nutraceutical treatment to skeletal muscle damage is an emerging area of research, driven by the need for new therapies for a range of muscle-associated diseases. L-Carnitine (CARN) is an essential nutrient and plays a key role in mitochondrial β-oxidation and in the ubiquitin-proteasome system regulation. As a dietary supplement to improve athletic performance, CARN has been studied for its potential to enhance β-oxidation. However, CARN effects on myogenesis, mitochondrial activity, and hypertrophy process are not completely elucidated. This in vitro study aims to investigate CARN role on skeletal muscle remodeling, differentiation process, and myotubes formation. We analyzed muscle differentiation and morphological features in C2C12 myoblasts exposed to 5 mM CARN. Our results showed that CARN was able to accelerate C2C12 myotubes formation and induce morphological changes, characterizing the start of hypertrophy process. In addition, CARN improved AKT activation and downstream cellular signaling pathways involved in skeletal muscle atrophy process prevention. Also, CARN positively regulated the pathways involved in oxidative stress defense. In this work, we provide an interesting novel mechanism of the potential therapeutic use of CARN to treat pathological conditions characterized by skeletal muscle morphological and functional impairment, oxidative stress production, and atrophy process in aging. Anna Montesano, Pamela Senesi, Livio Luzi, Stefano Benedini, and Ileana Terruzzi Copyright © 2015 Anna Montesano et al. All rights reserved. Poststroke Depression as a Factor Adversely Affecting the Level of Oxidative Damage to Plasma Proteins during a Brain Stroke Sun, 08 Mar 2015 09:09:39 +0000 http://www.hindawi.com/journals/omcl/2015/408745/ Poststroke depression, the second most serious psychosomatic complication after brain stroke, leads to delay of the rehabilitation process and is associated with an increased disability and cognitive impairment along with increase in term mortality. Research into the biochemical changes in depression is still insufficiently described. The aim of our study was therefore to evaluate the possible association between plasma protein oxidative/nitrative damages and the development of poststroke depression. We evaluated oxidative/nitrative modifications of specific proteins by measurement of 3-nitrotyrosine and carbonyl groups levels using ELISA test. Additionally, we checked differences in proteins thiol groups by spectrophotometric assay based on reaction between DTNB and thiols. We also evaluated catalase activity in erythrocytes measured as ability to decompose H2O2. Correlation analysis was performed using Spearman’s rank. We observed significant differences in all oxidative/nitrative stress parameters in brain stroke patients compared to healthy group. Our research shows that oxidative damage of proteins is correlated with the degree of poststroke depression, while nitrative changes do not show any relationship. We demonstrate a positive correlation between the concentration of carbonyl groups and the Geriatric Depression Scale and a negative correlation between the degree of depression and the concentration of -SH groups or catalase activity. Natalia Cichoń, Michał Bijak, Elżbieta Miller, Marta Niwald, and Joanna Saluk Copyright © 2015 Natalia Cichoń et al. All rights reserved.