Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer’s Disease Mon, 29 Jun 2015 08:29:59 +0000 http://www.hindawi.com/journals/omcl/2015/509654/ Alzheimer’s disease (AD) is a neurodegenerative disease that affects millions of people worldwide. Currently, there is no effective treatment for AD, which indicates the necessity to understand the pathogenic mechanism of this disorder. Extracellular aggregates of amyloid precursor protein (APP), called Aβ peptide and neurofibrillary tangles (NFTs), formed by tau protein in the hyperphosphorylated form are considered the hallmarks of AD. Accumulative evidence suggests that tau pathology and Aβ affect neuronal cells compromising energy supply, antioxidant response, and synaptic activity. In this context, it has been showed that mitochondrial function could be affected by the presence of tau pathology and Aβ in AD. Mitochondria are essential for brain cells function and the improvement of mitochondrial activity contributes to preventing neurodegeneration. Several reports have suggested that mitochondria could be affected in terms of morphology, bioenergetics, and transport in AD. These defects affect mitochondrial health, which later will contribute to the pathogenesis of AD. In this review, we will discuss evidence that supports the importance of mitochondrial injury in the pathogenesis of AD and how studying these mechanisms could lead us to suggest new targets for diagnostic and therapeutic intervention against neurodegeneration. Fabian A. Cabezas-Opazo, Katiana Vergara-Pulgar, María José Pérez, Claudia Jara, Cesar Osorio-Fuentealba, and Rodrigo A. Quintanilla Copyright © 2015 Fabian A. Cabezas-Opazo et al. All rights reserved. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans Sun, 28 Jun 2015 14:20:48 +0000 http://www.hindawi.com/journals/omcl/2015/837042/ Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol. J. Gambini, M. Inglés, G. Olaso, R. Lopez-Grueso, V. Bonet-Costa, L. Gimeno-Mallench, C. Mas-Bargues, K. M. Abdelaziz, M. C. Gomez-Cabrera, J. Vina, and C. Borras Copyright © 2015 J. Gambini et al. All rights reserved. Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide Production Sun, 28 Jun 2015 11:26:46 +0000 http://www.hindawi.com/journals/omcl/2015/787805/ Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate of progression to dementia. Significantly, use of CCBs ameliorated the negative effects of the presence of APOE-4 alleles on cognitive decline. To determine if CCBs could minimize amyloid beta peptide (Aβ1–42) production, H4 neuroglioma cultures transfected to overexpress APP were treated with various CCBs and Aβ1–42 levels and levels of proteins involved in Aβ production were quantified. Results show that treatment with nifedipine led to a significant decrease in levels of Aβ1–42, with no significant decrease in cell viability. Collectively, these data suggest that use of CCBs significantly diminishes the rate of progression to dementia and may minimize formation of Aβ1–42. Mark A. Lovell, Erin Abner, Richard Kryscio, Liou Xu, Shuling X. Fister, and Bert C. Lynn Copyright © 2015 Mark A. Lovell et al. All rights reserved. Novel Antioxidant Tripeptide “ACQ” Can Prevent UV-Induced Cell Death and Preserve the Number of Epidermal Stem Cells Thu, 25 Jun 2015 06:16:37 +0000 http://www.hindawi.com/journals/omcl/2015/359740/ We found that tripeptide “ACQ: alanine-cysteine-glutamine” has significant DPPH scavenging activity compared to that of glutathione. Antioxidant effects of ACQ were tested in in vitro and in vivo models. When treated with H2O2, mock treated fibroblasts and keratinocytes showed strong staining by H2DCFA. But, ACQ showed good protective effects against hydrogen peroxide treatment. When mice were fed for 2 or 4 weeks, similar protective effects were observed. In the control group, epidermis was severely damaged by UV irradiation and apoptotic keratinocytes were observed. There were also numerous TUNEL positive cells. But in the ACQ group, epidermis became thicker and there was no sign of severe damage. Interestingly, the number of p63 cells was also higher in ACQ fed mice. To confirm the stem cell rescuing effects of ACQ, three-dimensional skin samples were constructed. Results showed that ACQ increased the expression of integrin α6 and the number of p63 positive cells. These findings showed that ACQ has good antioxidant activity and may increase stem cell activities by the regulation of integrin α6. Hye-Ryung Choi, Jung-Won Shin, Jung-Im Na, Kyung-Mi Nam, Hyun-Sun Lee, and Kyoung-Chan Park Copyright © 2015 Hye-Ryung Choi et al. All rights reserved. Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway Wed, 24 Jun 2015 09:32:28 +0000 http://www.hindawi.com/journals/omcl/2015/606934/ Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA) is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders. Bingwu Zhong, Zhiping Hu, Jieqiong Tan, Tonglin Lu, Qiang Lei, Chunli Chen, and Liuwang Zeng Copyright © 2015 Bingwu Zhong et al. All rights reserved. Oxidative Stress and Antioxidant Defense in Endometriosis and Its Malignant Transformation Sun, 21 Jun 2015 12:13:56 +0000 http://www.hindawi.com/journals/omcl/2015/848595/ The aim of this study was to investigate the role of redox status in endometriosis and its malignant transformation. A search was conducted between 1990 and 2014 through the English language literature (online MEDLINE PubMed database) using the keywords endometriosis combined with malignant transformation, oxidative stress, and antioxidant defense. In benign endometriosis, autoxidation and Fenton reaction of hemoglobin from the ferrous Fe2+ (oxyhemoglobin) state to the ferric Fe3+ (methemoglobin) state lead to production of excess reactive oxygen species (ROS) such as and . Hemoglobin, heme, and iron derivatives in endometriotic cysts cause distortion in the homeostatic redox balance. Excess oxidative stress could trigger DNA damage and cell death. In contrast, endometriosis-associated ovarian cancer (EAOC) might be associated with an effective antioxidant defense, including heme oxygenases, cytochrome P450 family, and glutathione transferase family. The pattern of redox balance supports that enhanced antioxidants may be involved in the pathogenesis of malignant transformation. In conclusion, oxidant/antioxidant balance function is a double-edged sword, promoting cell death or carcinogenesis. Upregulation of antioxidant functions in endometriotic cyst may result in restoration of cell survival and subsequent malignant transformation. Takuya Iwabuchi, Chiharu Yoshimoto, Hiroshi Shigetomi, and Hiroshi Kobayashi Copyright © 2015 Takuya Iwabuchi et al. All rights reserved. Melatonin Attenuates Oxidative Damage Induced by Acrylamide In Vitro and In Vivo Sun, 21 Jun 2015 11:35:16 +0000 http://www.hindawi.com/journals/omcl/2015/703709/ Acrylamide (ACR) has been classified as a neurotoxic agent in animals and humans. Melatonin (MT) has been shown to be potentially effective in preventing oxidative stress related neurodegenerative disorders. In this study, whether MT exerted a protective effect against ACR-induced oxidative damage was investigated. Results in cells showed that reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after ACR treatment for 24 h. MT preconditioning or cotreatment with ACR reduced ROS and MDA products, whereas the inhibitory effect of MT on oxidant generation was attenuated by blocking the MT receptor. Increased DNA fragmentation caused by ACR was significantly decreased by MT coadministration. In vivo, rats at 40 mg/kg/day ACR by gavage for 12 days showed weight loss and gait abnormality, Purkinje cell nuclear condensation, and DNA damage in rat cerebellum. MT (i.p) cotreatment with ACR not only recovered weight and gait of rats, but also decreased nuclear condensation and DNA damage in rat cerebellum. Using MDA generation, glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in rat cerebellum as indicators, MT alleviated ACR-induced lipid peroxidation and depressed antioxidant capacity. Our results suggest that MT effectively prevents oxidative damage induced by ACR. Xiaoqi Pan, Lanlan Zhu, Huiping Lu, Dun Wang, Qing Lu, and Hong Yan Copyright © 2015 Xiaoqi Pan et al. All rights reserved. Influence of Selenium Content in the Culture Medium on Protein Profile of Yeast Cells Candida utilis ATCC 9950 Sun, 21 Jun 2015 07:46:13 +0000 http://www.hindawi.com/journals/omcl/2015/659750/ Selenium is an essential trace element for human health and it has been recognized as a component of several selenoproteins with crucial biological functions. It has been identified as a component of active centers of many enzymes, as well as integral part of biologically active complexes. The aim of the study was to evaluate the protein content and amino acid profile of the protein of fodder yeast Candida utilis ATCC 9950 cultured in media control and experimental enriched selenium. Protein analysis was performed using SDS-PAGE method consisting of polyacrylamide gel electrophoresis in the presence of SDS. The highest contents of soluble protein (49,5 mg/g) were found in yeast cells after 24-hour culture conducted in control (YPD) medium. In the presence of selenium there were determined small amounts of protein content. With increasing time of yeast culture (to 72 hours) the control and experimental media were reported to reduce soluble protein content. In electropherogram proteins from control cultures was observed the presence of 10 protein fractions, but in all the experimental cultures (containing 20, 30, and 40 mg/L selenium) of 14 protein fractions. On the basis of the molecular weights of proteins, it can be concluded that they were among others: selenoprotein 15 kDa and selenoprotein 18 kDa. Marek Kieliszek, Stanisław Błażejak, and Anna Bzducha-Wróbel Copyright © 2015 Marek Kieliszek et al. All rights reserved. Efficacy of N-Acetylcysteine, Glutathione, and Ascorbic Acid in Acute Toxicity of Paraoxon to Wistar Rats: Survival Study Thu, 18 Jun 2015 09:21:57 +0000 http://www.hindawi.com/journals/omcl/2015/329306/ There are a great number of reports with assertions that oxidative stress is produced by organophosphorus compound (OPC) poisoning and is a cofactor of mortality and morbidity in OPC toxicity. In addition, antioxidants have been suggested as adjuncts to standard therapy. However, there is no substantial evidence for the benefit of the use of antioxidants in survival after acute intoxication of OPCs. The present study was conducted to assess the effectiveness of three non-enzymatic antioxidants (NEAOs), N-acetylcysteine (NAC), glutathione (GSH), and ascorbic acid (AA), in acute intoxication of adult male Wister rats with paraoxon. The efficacy of the antioxidants was estimated as both a pretreatment and a concurrent application along with the standard oxime, pralidoxime (2-PAM). Relative risk of death after 48 hours of application was estimated by Cox regression analysis. The results revealed no benefit of either tested NEAO to the improvement in survival of experimental rats. The application of these antioxidants was found to be deleterious when administered along with pralidoxime compared to the treatment with pralidoxime alone. It has been concluded that the tested non-enzymatic antioxidants are not useful in acute toxicity for improving survival rates. However, the individual toxic dynamics of diversified OPCs should not be overlooked and further studies with different OPCs are suggested. Syed M. Nurulain, Shreesh Ojha, Kornelia Tekes, Mohammad Shafiullah, Huba Kalasz, and Abdu Adem Copyright © 2015 Syed M. Nurulain et al. All rights reserved. Heterogeneity of Systemic Oxidative Stress Profiles in COPD: A Potential Role of Gender Wed, 17 Jun 2015 09:37:51 +0000 http://www.hindawi.com/journals/omcl/2015/201843/ Oxidative stress (OS) plays a key role in the muscle impairment and exercise capacity of COPD patients. However, the literature reveals that systemic OS markers show great heterogeneity, which may hinder the prescription of effective antioxidant supplementation. This study therefore aimed to identify OS markers imbalance of COPD patients, relative to validated normal reference values, and to investigate the possibility of systemic OS profiles. We measured systemic enzymatic/nonenzymatic antioxidant and lipid peroxidation (LP) levels in 54 stable COPD patients referred for a rehabilitation program. The main systemic antioxidant deficits in these patients concerned vitamins and trace elements. Fully 89% of the COPD patients showed a systemic antioxidant imbalance which may have caused the elevated systemic LP levels in 69% of them. Interestingly, two patient profiles (clusters 3 and 4) had a more elevated increase in LP combined with increased copper and/or decreased vitamin C, GSH, and GPx. Further analysis revealed that the systemic LP level was higher in COPD women and associated with exercise capacity. Our present data therefore support future supplementations with antioxidant vitamins and trace elements to improve exercise capacity, but COPD patients will probably show different positive responses. Jonathan Maury, Farés Gouzi, Philippe De Rigal, Nelly Heraud, Joël Pincemail, Nicolas Molinari, Pascal Pomiès, Dalila Laoudj-Chenivesse, Jacques Mercier, Christian Préfaut, and Maurice Hayot Copyright © 2015 Jonathan Maury et al. All rights reserved. High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery Tue, 16 Jun 2015 12:30:24 +0000 http://www.hindawi.com/journals/omcl/2015/125106/ Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde (MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including , , , and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction. Qian Yang, Wei Wu, Qian Li, Chan Chen, Ronghua Zhou, Yanhua Qiu, Ming Luo, Zhaoxia Tan, Shen Li, Gang Chen, Wentao Zhou, Jiaxin Liu, Chengmin Yang, Jin Liu, and Tao Li Copyright © 2015 Qian Yang et al. All rights reserved. Glutathione Supplementation Attenuates Oxidative Stress and Improves Vascular Hyporesponsiveness in Experimental Obstructive Jaundice Tue, 16 Jun 2015 08:59:18 +0000 http://www.hindawi.com/journals/omcl/2015/486148/ We investigated the protective effects and mechanism of glutathione (GSH) on vascular hyporesponsiveness induced by bile duct ligation (BDL) in a rat model. Seventy-two male Sprague-Dawley rats were randomly divided into four groups: a NS group, a GSH group, a BDL + NS group, and a BDL + GSH group. GSH was administrated into rats in the GSH and BDL + GSH groups by gastric gavage. An equal volume of normal saline was, respectively, given in the NS group and BDL + NS group. Blood was gathered for serological determination and thoracic aorta rings were isolated for measurement of isometric tension. Obstructive jaundice led to a significant increase in the serum total bilirubin, AST, and ALT levels. The proinflammatory cytokines levels (TNF-α and IL-1β), concentration of NO, and oxidative stress markers (MDA and 3-NT) were increased as well. All of those were reduced by the treatment of GSH. Meanwhile, contraction of aorta rings to NA and vasorelaxation to ACh or SNP in the BDL group rats were markedly decreased, while GSH administration reversed this change. Our findings suggested that GSH supplementation attenuated overexpressed ONOO(−) from the reaction of excessive NO with and protected against obstructive jaundice-induced vascular hyporesponsiveness in rats. Jiaying Chen, Feixiang Wu, Yue Long, and Weifeng Yu Copyright © 2015 Jiaying Chen et al. All rights reserved. The Protective Effects of Salidroside from Exhaustive Exercise-Induced Heart Injury by Enhancing the PGC-1α–NRF1/NRF2 Pathway and Mitochondrial Respiratory Function in Rats Tue, 16 Jun 2015 08:07:20 +0000 http://www.hindawi.com/journals/omcl/2015/876825/ Objective. To test the hypothesis that salidroside (SAL) can protect heart from exhaustive exercise-induced injury by enhancing mitochondrial respiratory function and mitochondrial biogenesis key signaling pathway PGC-1α–NRF1/NRF2 in rats. Methods. Male Sprague-Dawley rats were divided into 4 groups: sedentary (C), exhaustive exercise (EE), low-dose SAL (LS), and high-dose SAL (HS). After one-time exhaustive swimming exercise, we measured the changes in cardiomyocyte ultrastructure and cardiac marker enzymes and mitochondrial electron transport system (ETS) complexes activities in situ. We also measured mitochondrial biogenesis master regulator PGC-1α and its downstream transcription factors, NRF1 and NRF2, expression at gene and protein levels. Results. Compared to C group, the EE group showed marked myocardium ultrastructure injury and decrease of mitochondrial respiratory function and protein levels of PGC-1α, NRF1, and NRF2  but a significant increase of PGC-1α, NRF1, and NRF2 genes levels ; compared to EE group, SAL ameliorated myocardium injury, increased mitochondrial respiratory function , and elevated both gene and protein levels of PGC-1α, NRF-1, and NRF-2. Conclusion. Salidroside can protect the heart from exhaustive exercise-induced injury. It might act by improving myocardial mitochondrial respiratory function by stimulating the expression of PGC-1α–NRF1/NRF2 pathway. Zheng Ping, Long-fei Zhang, Yu-juan Cui, Yu-mei Chang, Cai-wu Jiang, Zhen-zhi Meng, Peng Xu, Hai-yan Liu, Dong-ying Wang, and Xue-bin Cao Copyright © 2015 Zheng Ping et al. All rights reserved. Mechanical Ventilation Induces an Inflammatory Response in Preinjured Lungs in Late Phase of Sepsis Tue, 16 Jun 2015 07:57:55 +0000 http://www.hindawi.com/journals/omcl/2015/364020/ Mechanical ventilation (MV) may amplify the lung-specific inflammatory response in preinjured lungs by elevating cytokine release and augmenting damage to the alveolar integrity. In this study, we test the hypothesis that MV exerts different negative impacts on inflammatory response at different time points of postlung injury. Basic lung injury was induced by cecal ligation and puncture (CLP) surgery in rats. Physiological indexes including blood gases were monitored during MV and samples were assessed following each experiment. Low (tidal volume) MV caused a slight increase in cytokine release and tissue damage at day 1 and day 4 after sepsis induced lung injury, while cytokine release from the lungs in the two moderately ventilated groups was amplified. Interestingly, in the two groups where rats received low MV, we found that infiltration of inflammatory cells was only profound at day 4 after CLP. Marked elevation of protein leakage indicated a compromise in alveolar integrity in rats that received moderate MV at day 4 following CLP, correlating with architectural damage to the alveoli. Our study indicates that preinjured lungs are more sensitive to mechanical MV at later phases of sepsis, and this situation may be a result of differing immune status. Wei Xuan, Quanjun Zhou, Shanglong Yao, Qingzhu Deng, Tingting Wang, and Qingping Wu Copyright © 2015 Wei Xuan et al. All rights reserved. Oxidative Stress and Lung Ischemia-Reperfusion Injury Tue, 16 Jun 2015 07:56:30 +0000 http://www.hindawi.com/journals/omcl/2015/590987/ Ischemia-reperfusion (IR) injury is directly related to the formation of reactive oxygen species (ROS), endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients. Renata Salatti Ferrari and Cristiano Feijó Andrade Copyright © 2015 Renata Salatti Ferrari and Cristiano Feijó Andrade. All rights reserved. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits Tue, 16 Jun 2015 07:54:03 +0000 http://www.hindawi.com/journals/omcl/2015/624819/ Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties. Bingbing Liu, Weihua Huang, Xiaoshan Xiao, Yao Xu, Songmei Ma, and Zhengyuan Xia Copyright © 2015 Bingbing Liu et al. All rights reserved. Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model Tue, 16 Jun 2015 07:37:19 +0000 http://www.hindawi.com/journals/omcl/2015/380403/ Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS). Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP) model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia) in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56%) rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant). Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline () and methylprednisolone () groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (). Proinflammatory cytokines TNF-α and IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (all ). In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain. Suryamin Liman, Chi Wai Cheung, Kar Lok Wong, Wai Tai, Qiu Qiu, Kwok Fu Ng, Siu Wai Choi, and Michael Irwin Copyright © 2015 Suryamin Liman et al. All rights reserved. Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway Tue, 16 Jun 2015 07:28:45 +0000 http://www.hindawi.com/journals/omcl/2015/585297/ Background. Activation of the adenosine receptor (R) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the R-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by R. Methods and Results. C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selective R antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selective R agonist, significantly reduced myocardial infarct size, and its protective effect could be blocked by either ATL-801 or wortmannin. BAY 60-6583 increased phosphorylated Akt (p-Akt) levels in the heart at 10 min of reperfusion, and this phosphorylation could also be blocked by ATL-801 or wortmannin. Furthermore, BAY 60-6583 significantly increased M2 macrophages and decreased M1 macrophage and neutrophils infiltration in reperfused hearts, which also could be blocked by wortmannin. Meanwhile, confocal imaging studies showed that the majority of Akt phosphorylation in the heart was colocalized to CD206+ cells in both control and BAY 60-6583 pretreated hearts. Conclusion. Our results indicated that pretreatment with BAY 60-6583 protects the heart against myocardial IR injury by its anti-inflammatory effects, probably by modulating macrophages phenotype switching via a PI3K/Akt pathway. Yikui Tian, Bryan A. Piras, Irving L. Kron, Brent A. French, and Zequan Yang Copyright © 2015 Yikui Tian et al. All rights reserved. OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells Tue, 16 Jun 2015 07:25:02 +0000 http://www.hindawi.com/journals/omcl/2015/683197/ Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use. Zhong-Jie Liu, Wei Zhao, Qing-Guo Zhang, Le Li, Lu-Ying Lai, Shan Jiang, and Shi-Yuan Xu Copyright © 2015 Zhong-Jie Liu et al. All rights reserved. Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice Tue, 16 Jun 2015 06:32:32 +0000 http://www.hindawi.com/journals/omcl/2015/843721/ Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway. Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R. Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α but decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-α and MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA. Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway. Ying Jiang, Zhen Zhou, Qing-tao Meng, Qian Sun, Wating Su, Shaoqing Lei, Zhengyuan Xia, and Zhong-yuan Xia Copyright © 2015 Ying Jiang et al. All rights reserved. Effects of Cyclosporine on Reperfusion Injury in Patients: A Meta-Analysis of Randomized Controlled Trials Tue, 16 Jun 2015 06:25:23 +0000 http://www.hindawi.com/journals/omcl/2015/287058/ Mitochondrial permeability transition pore (mPTP) opening due to its role in regulating ROS generation contributes to cardiac reperfusion injury. In animals, cyclosporine (cyclosporine A, CsA), an inhibitor of mPTP, has been found to prevent reperfusion injury following acute myocardial infarction. However, the effects of CsA in reperfusion injury in clinical patients are not elucidated. We performed a meta-analysis using published clinical studies and electronic databases. Relevant data were extracted using standardized algorithms and additional data were obtained directly from investigators as indicated. Five randomized controlled blind trials were included in our meta-analysis. The clinical outcomes including infarct size (SMD: −0.41; 95% CI: −0.81, 0.01; = 0.058), left ventricular ejection fraction (LVEF) (SMD: 0.20; 95% CI: −0.02, 0.42; = 0.079), troponin I (TnI) (SMD: −0.21; 95% CI: −0.49, 0.07; = 0.149), creatine kinase (CK) (SMD: −0.32; 95% CI: −0.98, 0.35; = 0.352), and creatine kinase-MB isoenzyme (CK-MB) (SMD: −0.06; 95% CI: −0.35, 0.23; = 0.689) suggested that there is no significant difference on cardiac function and injury with or without CsA treatment. Our results indicated that, unlike the positive effects of CsA in animal models, CsA administration may not protect heart from reperfusion injury in clinical patients with myocardial infarction. Kangxing Song, Shuxia Wang, and Dake Qi Copyright © 2015 Kangxing Song et al. All rights reserved. Organ-Protective Effects of Red Wine Extract, Resveratrol, in Oxidative Stress-Mediated Reperfusion Injury Tue, 16 Jun 2015 06:00:37 +0000 http://www.hindawi.com/journals/omcl/2015/568634/ Resveratrol, a polyphenol extracted from red wine, possesses potential antioxidative and anti-inflammatory effects, including the reduction of free radicals and proinflammatory mediators overproduction, the alteration of the expression of adhesion molecules, and the inhibition of neutrophil function. A growing body of evidence indicates that resveratrol plays an important role in reducing organ damage following ischemia- and hemorrhage-induced reperfusion injury. Such protective phenomenon is reported to be implicated in decreasing the formation and reaction of reactive oxygen species and pro-nflammatory cytokines, as well as the mediation of a variety of intracellular signaling pathways, including the nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, deacetylase sirtuin 1, mitogen-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, hemeoxygenase-1, and estrogen receptor-related pathways. Reperfusion injury is a complex pathophysiological process that involves multiple factors and pathways. The resveratrol is an effective reactive oxygen species scavenger that exhibits an antioxidative property. In this review, the organ-protective effects of resveratrol in oxidative stress-related reperfusion injury will be discussed. Fu-Chao Liu, Hsin-I Tsai, and Huang-Ping Yu Copyright © 2015 Fu-Chao Liu et al. All rights reserved. Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of Mito in Energy Homeostasis Mon, 15 Jun 2015 14:27:28 +0000 http://www.hindawi.com/journals/omcl/2015/756576/ Mitochondrial ATP-sensitive potassium channel (mito) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. Mito status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mito opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mito opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mito and suggested that the mito opening plays a physiologic role in triggering cardiomyocytes’ energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI. Song Cao, Yun Liu, Wenting Sun, Li Zhao, Lin Zhang, Xinkui Liu, and Tian Yu Copyright © 2015 Song Cao et al. All rights reserved. The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer’s Disease Mon, 15 Jun 2015 13:23:33 +0000 http://www.hindawi.com/journals/omcl/2015/352723/ Alzheimer’s disease (AD) is the most common form of dementia. The pathological hallmarks of AD are amyloid plaques [aggregates of amyloid-beta (Aβ)] and neurofibrillary tangles (aggregates of tau). Growing evidence suggests that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than Aβ plaques. Oxidative stress is a prominent early event in the pathogenesis of AD and is therefore believed to contribute to tau hyperphosphorylation. Several studies have shown that the autophagic pathway in neurons is important under physiological and pathological conditions. Therefore, this pathway plays a crucial role for the degradation of endogenous soluble tau. However, the relationship between oxidative stress, tau protein hyperphosphorylation, autophagy dysregulation, and neuronal cell death in AD remains unclear. Here, we review the latest progress in AD, with a special emphasis on oxidative stress, tau hyperphosphorylation, and autophagy. We also discuss the relationship of these three factors in AD. Zhenzhen Liu, Tao Li, Ping Li, Nannan Wei, Zhiquan Zhao, Huimin Liang, Xinying Ji, Wenwu Chen, Mengzhou Xue, and Jianshe Wei Copyright © 2015 Zhenzhen Liu et al. All rights reserved. Dexmedetomidine Analgesia Effects in Patients Undergoing Dental Implant Surgery and Its Impact on Postoperative Inflammatory and Oxidative Stress Mon, 15 Jun 2015 13:07:39 +0000 http://www.hindawi.com/journals/omcl/2015/186736/ The aim of the study was to determine whether or not dexmedetomidine- (DEX-) based intravenous infusion in dental implantation can provide better sedation and postoperative analgesia via suppressing postoperative inflammation and oxidative stress. Sixty patients were randomly assigned to receive either DEX (group D) or midazolam (group M). Recorded variables were vital sign (SBP/HR/RPP/SpO2/RR), visual analogue scale (VAS) pain scores, and observer’s assessment of alertness/sedation scale (OAAS) scores. The plasma levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), antioxidant superoxide dismutase (SOD), and the lipid peroxidation product malondialdehyde (MDA) were detected at baseline and after 2, 4, and 24 h of drug administration. The VAS pain scores and OAAS scores were significantly lower for patients in group D compared to group M. The plasma levels of TNF-α, IL-6, and MDA were significantly lower in group D patients than those in group M at 2 h and 4 h. In group M, SOD levels decreased as compared to group D at 2 h and 4 h. The plasma levels of TNF-α, IL-6, and MDA were positively correlated with VAS pain scores while SOD negatively correlated with VAS pain scores. Therefore, DEX appears to provide better sedation during office-based artificial tooth implantation. DEX offers better postoperative analgesia via anti-inflammatory and antioxidation pathway. Sisi Li, Yang Yang, Cong Yu, Ying Yao, Yujia Wu, Lian Qian, and Chi Wai Cheung Copyright © 2015 Sisi Li et al. All rights reserved. Body Composition, Lipid Profile, Adipokine Concentration, and Antioxidant Capacity Changes during Interventions to Treat Overweight with Exercise Programme and Whole-Body Cryostimulation Mon, 15 Jun 2015 12:07:01 +0000 http://www.hindawi.com/journals/omcl/2015/803197/ The aim of this study was to determine the effect of six-month-long physical exercise programme with a two-time exposure to whole-body cryostimulation (WBC) in 20 sessions on antioxidant enzyme activities, lipid profile, and body composition changes in obese people (30 adult subjects; BMI = 30.39 ± 4.31 kg/m2). Blood samples were taken before the programme, one month following the exercise programme, before and after the first WBC treatment, six months following the exercise programme, after the second WBC treatment, and finally one month after the intervention. Six months of moderate aerobic activity combined with WBC did not change body mass or fat and lean body mass percentages, or circulating adiponectin, leptin, and resistin concentrations. In response to intervention a significant decrease in the level of low-density lipoprotein and triglycerides was observed, with a slight increase in high-density lipoprotein concentration. The nature of changes in the activity of respective antioxidant enzymes was not identical. After one month of increased physical activity, a significant decrease in superoxide dismutase, catalase, and glutathione reductase activities was observed (13%, 8%, and 70%, resp.). The SOD activity increased significantly after successive whole-body cryostimulation sessions. As regards catalase, a significant progressive decrease in its activity was observed. Anna Lubkowska, Wioleta Dudzińska, Iwona Bryczkowska, and Barbara Dołęgowska Copyright © 2015 Anna Lubkowska et al. All rights reserved. Octreotide Protects the Mouse Retina against Ischemic Reperfusion Injury through Regulation of Antioxidation and Activation of NF-κB Sun, 14 Jun 2015 07:38:36 +0000 http://www.hindawi.com/journals/omcl/2015/970156/ Somatostatin (SST), an endogenous peptide, may exert anti-inflammatory and neuroprotective effects on retinal injury induced by ischemia. Retinal ischemic reperfusion (I/R) injury always produces many reactive oxygen species (ROS), which can aggravate the tissue damage. The effects of octreotide (OCT), a SST analogue, on retinal I/R injury and ROS formation, are not very clear. In this study, we observed the effects of OCT on morphological changes, oxidative stress, and cell death, induced by retinal I/R injury. The activation of nuclear factor κB (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) were further evaluated in I/R retina treated with or without OCT. The retinal layer thickness was increased at 1 day after I/R and decreased at 7 days after I/R . This effect was associated with increase in MDA and ROS levels . The Tunel-positive cells increased and the number of ganglion cell layer (GCL) neurons decreased significantly after I/R injury. The expression of p-p65 and ICAM-1 increased significantly in I/R retinas . Each effect was markedly attenuated by application of OCT. These data indicate that OCT protects the retina against retinal I/R damage, which could be through inhibition of oxidative stress and downregulation of NF-κB and ICAM-1 expression. Jun Wang, Ziqiang Sun, Junsheng Shen, Dongdong Wu, Fang Liu, Ruisheng Yang, Shaoping Ji, Ailing Ji, and Yanzhang Li Copyright © 2015 Jun Wang et al. All rights reserved. Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats Sun, 14 Jun 2015 06:52:11 +0000 http://www.hindawi.com/journals/omcl/2015/787561/ The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP), we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h) for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM) for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1, MIP-2, and KC) and cytokines (IL-1 and TNF-) in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders. Mounira Tlili, Sonia Rouatbi, Badreddine Sriha, Khémais Ben Rhouma, Mohsen Sakly, David Vaudry, Olivier Wurtz, and Olfa Tebourbi Copyright © 2015 Mounira Tlili et al. All rights reserved. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress Thu, 11 Jun 2015 07:21:51 +0000 http://www.hindawi.com/journals/omcl/2015/183928/ Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk), which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols. Patrizia Ferroni, Silvia Riondino, Oreste Buonomo, Raffaele Palmirotta, Fiorella Guadagni, and Mario Roselli Copyright © 2015 Patrizia Ferroni et al. All rights reserved. L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis Wed, 10 Jun 2015 13:31:33 +0000 http://www.hindawi.com/journals/omcl/2015/351698/ A moderate elevation of reactive oxygen species (ROS) production and a mild inhibition of mitochondrial respiratory chain have been associated with a health promotion and a lifespan extension in several animal models of aging. Here, we tested whether this phenomenon called mitohormesis could be mediated by L-lactate. The treatment with 5 mM L-lactate significantly increased H2O2 production and slightly inhibited the respiration in cultured skin fibroblasts and in isolated mitochondria. The L-lactate exposure was associated with oxidation of intracellular glutathione, phosphorylation of 5′AMP-activated protein kinase (AMPK), and induction of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) transcription. A replicative aging of fibroblasts (L0) with a constant (LC), or intermittent 5 mM L-lactate (LI) in media showed that the high-passage LI fibroblasts have higher respiration, lower H2O2 release, and lower secretion of L-lactate compared to L0 and LC. This protection against mitochondrial dysfunction in LI cells was associated with lower activity of mechanistic target of rapamycin complex 1 (mTORC1), less signs of cellular senescence, and increased autophagy compared to L0 and LC. In conclusion, we demonstrated that intermittent but not constant exposure to L-lactate triggers mitohormesis, prevents aging-associated mitochondrial dysfunction, and improves other markers of aging. Jaroslav Zelenka, Aleš Dvořák, and Lukáš Alán Copyright © 2015 Jaroslav Zelenka et al. All rights reserved.