Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Protective Effect of Parsley Juice (Petroselinum crispum, Apiaceae) against Cadmium Deleterious Changes in the Developed Albino Mice Newborns (Mus musculus) Brain Sun, 07 Feb 2016 11:12:07 +0000 http://www.hindawi.com/journals/omcl/2016/2646840/ Parsley was used as a probe of the current experiment to prevent the behavioral, morphological and biochemical changes in the newborn brain following the administration of cadmium (Cd) to the pregnant mice. The nonanesthetized pregnant mice were given daily parsley juice (Petroselinum crispum) at doses of 20 mg/kg and 10 mg/kg. Pregnant mothers were given Cd at a dose of 30 mg/kg divided into 3 equal times. The newborns have been divided into 6 groups: Group A, mothers did not take treatment; Groups B and C, mothers were treated with low and high dose of parsley, respectively; Group D, mothers were treated only with Cd (perinatal intoxication); Groups E and F, mothers were treated with Cd doses and protected by low and high doses of parsley, respectively. Light microscopy showed that Cd-induced neuronal degeneration by chromatolysis and pyknosis in the brain regions. The low dose of parsley 10 g/kg/day exhibited significant effects in neutralizing and reducing the deleterious changes due to Cd exposure during pregnancy on the behavioral activities, neurotransmitters, oxidative stress, and brain neurons morphology of the mice newborns. Ahmed A. Allam, Salah N. Maodaa, Rasha Abo-Eleneen, and Jamaan Ajarem Copyright © 2016 Ahmed A. Allam et al. All rights reserved. Periodic Exposure of Keratinocytes to Cold Physical Plasma: An In Vitro Model for Redox-Related Diseases of the Skin Thu, 04 Feb 2016 09:43:47 +0000 http://www.hindawi.com/journals/omcl/2016/9816072/ Oxidative stress illustrates an imbalance between radical formation and removal. Frequent redox stress is critically involved in many human pathologies including cancer, psoriasis, and chronic wounds. However, reactive species pursue a dual role being involved in signaling on the one hand and oxidative damage on the other. Using a HaCaT keratinocyte cell culture model, we investigated redox regulation and inflammation to periodic, low-dose oxidative stress after two, six, eight, ten, and twelve weeks. Chronic redox stress was generated by recurrent incubation with cold physical plasma-treated cell culture medium. Using transcriptome microarray technology, we identified both acute ROS-stress responses as well as numerous adaptions after several weeks of redox challenge. We determined a differential expression (2-fold, FDR < 0.01, ) of 260 genes that function in inflammation and redox homeostasis, such as cytokines (e.g., IL-6, IL-8, and IL-10), growth factors (e.g., CSF2, FGF, and IGF-2), and antioxidant enzymes (e.g., HMOX, NQO1, GPX, and PRDX). Apoptotic signaling was affected rather modestly, especially in p53 downstream targets (e.g., BCL2, BBC3, and GADD45). Strikingly, the cell-protective heat shock protein HSP27 was strongly upregulated (). These results suggested cellular adaptions to frequent redox stress and may help to better understand the inflammatory responses in redox-related diseases. Anke Schmidt, Thomas von Woedtke, and Sander Bekeschus Copyright © 2016 Anke Schmidt et al. All rights reserved. Anti-Inflammatory Therapy Modulates Nrf2-Keap1 in Kidney from Rats with Diabetes Wed, 03 Feb 2016 13:33:38 +0000 http://www.hindawi.com/journals/omcl/2016/4693801/ This study addressed the relationship of proinflammatory cytokines and Nrf2-Keap1 system in diabetic nephropathy. The experimental groups were control, diabetic, and diabetic treated with mycophenolate mofetil (MMF). The renal function, proinflammatory and profibrotic cytokines, oxidative stress, morphology, and nephrin expression were assessed. Diabetic group showed impaired renal function in association with oxidative stress and decreased Nrf2 nuclear translocation. These results were associated with increased mesangial matrix index, interstitial fibrosis, and increased nephrin expression in cortex and urine excretion. Additionally, interleukin-1β, IL-6, and transforming growth factor-β1 were increased in plasma and kidney. MMF treatment conserved renal function, prevented renal structural alterations, and partially prevented the proinflammatory and profibrotic cytokines overexpression. Despite that MMF treatment induced nephrin overexpression in renal tissue, preventing its urinary loss. MMF salutary effects were associated with a partial prevention of oxidative stress, increased Nrf2 nuclear translocation, and conservation of antioxidant enzymes in renal tissue. In conclusion, our results confirm that inflammation is a key factor in the progression of diabetic nephropathy and suggest that treatment with MMF protects the kidney by an antioxidant mechanism, possibly regulated at least in part by the Nrf2/Keap1 system, in addition to its well-known anti-inflammatory effects. Abraham Said Arellano-Buendía, Montserrat Tostado-González, Fernando Enrique García-Arroyo, Magdalena Cristóbal-García, María Lilia Loredo-Mendoza, Edilia Tapia, Laura-Gabriela Sánchez-Lozada, and Horacio Osorio-Alonso Copyright © 2016 Abraham Said Arellano-Buendía et al. All rights reserved. An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations Wed, 03 Feb 2016 11:41:53 +0000 http://www.hindawi.com/journals/omcl/2016/7053897/ As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations. Alison Curnow and Sara J. Owen Copyright © 2016 Alison Curnow and Sara J. Owen. All rights reserved. HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis Wed, 03 Feb 2016 07:15:24 +0000 http://www.hindawi.com/journals/omcl/2016/9012580/ HCV (hepatitis C virus) is a member of the Flaviviridae family that contains a single-stranded positive-sense RNA genome of approximately 9600 bases. HCV is a major causative agent for chronic liver diseases such as steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma which are caused by multifactorial processes. Elevated levels of reactive oxygen species (ROS) are considered as a major factor contributing to HCV-associated pathogenesis. This review summarizes the mechanisms involved in formation of ROS in HCV replicating cells and describes the interference of HCV with ROS detoxifying systems. The relevance of ROS for HCV-associated pathogenesis is reviewed with a focus on the interference of elevated ROS levels with processes controlling liver regeneration. The overview about the impact of ROS for the viral life cycle is focused on the relevance of autophagy for the HCV life cycle and the crosstalk between HCV, elevated ROS levels, and the induction of autophagy. Regina Medvedev, Daniela Ploen, and Eberhard Hildt Copyright © 2016 Regina Medvedev et al. All rights reserved. Isosteviol Sensitizes sarcKATP Channels towards Pinacidil and Potentiates Mitochondrial Uncoupling of Diazoxide in Guinea Pig Ventricular Myocytes Tue, 02 Feb 2016 13:01:47 +0000 http://www.hindawi.com/journals/omcl/2016/6362812/ channel is an important mediator or factor in physiological and pathological metabolic pathway. Activation of channel has been identified to be a critical step in the cardioprotective mechanism against IR injury. On the other hand, desensitization of the channel to its opener or the metabolic ligand ATP in pathological conditions, like cardiac hypertrophy, would decrease the adaption of myocardium to metabolic stress and is a disadvantage for drug therapy. Isosteviol, obtained by acid hydrolysis of stevioside, has been demonstrated to play a cardioprotective role against diseases of cardiovascular system, like anti-IR injury, antihypertension, antihyperglycemia, and so forth. The present study investigated the effect of isosteviol (STV) on sarc channel current induced by pinacidil and mitochondrial flavoprotein oxidation induced by diazoxide. Our results showed that preincubating cells with STV not only increased the current amplitude and activating rate of sarc channels induced by pinacidil but also potentiated diazoxide-elicited oxidation of flavoprotein in mitochondria. Zhuo Fan, Ting Wen, Yaoxu Chen, Lijie Huang, Wei Lin, Chunxia Yin, and Wen Tan Copyright © 2016 Zhuo Fan et al. All rights reserved. Exercise, Free Radical Metabolism, and Aging: Cellular and Molecular Processes Tue, 02 Feb 2016 08:50:27 +0000 http://www.hindawi.com/journals/omcl/2016/3813680/ Geraint D. Florida-James, Rickie Simpson, Gareth Davison, and Graeme Close Copyright © 2016 Geraint D. Florida-James et al. All rights reserved. Neurodegeneration, Neurogenesis, and Oxidative Stress 2015 Tue, 02 Feb 2016 08:00:12 +0000 http://www.hindawi.com/journals/omcl/2016/7632025/ Renata Santos, Anne-Laure Bulteau, and Cláudio M. Gomes Copyright © 2016 Renata Santos et al. All rights reserved. Soy Isoflavone Protects Myocardial Ischemia/Reperfusion Injury through Increasing Endothelial Nitric Oxide Synthase and Decreasing Oxidative Stress in Ovariectomized Rats Mon, 01 Feb 2016 13:59:47 +0000 http://www.hindawi.com/journals/omcl/2016/5057405/ There is a special role for estrogens in preventing and curing cardiovascular disease in women. Soy isoflavone (SI), a soy-derived phytoestrogen, has similar chemical structure to endogenous estrogen-estradiol. We investigate to elucidate the protective mechanism of SI on myocardial ischemia/reperfusion (MI/R) injury. Female SD rats underwent bilateral ovariectomy. One week later, rats were randomly divided into several groups, sham ovariectomy (control group), ovariectomy with MI/R, or ovariectomy with sham MI/R. Other ovariectomy rats were given different doses of SI or 17β-estradiol (E2). Four weeks later, they were exposed to 30 minutes of left coronary artery occlusion followed by 6 or 24 hours of reperfusion. SI administration significantly reduced myocardial infarct size and improved left ventricle function and restored endothelium-dependent relaxation function of thoracic aortas after MI/R in ovariectomized rats. SI also decreased serum creatine kinase and lactate dehydrogenase activity, reduced plasma malonaldehyde, and attenuated oxidative stress in the myocardium. Meanwhile, SI increased phosphatidylinositol 3 kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) signal pathway. SI failed to decrease infarct size of hearts with I/R in ovariectomized rats if PI3K was inhibited. Overall, these results indicated that SI protects myocardial ischemia/reperfusion injury in ovariectomized rats through increasing PI3K/Akt/eNOS signal pathway and decreasing oxidative stress. Yan Tang, Shuangyue Li, Ping Zhang, Jinbiao Zhu, Guoliang Meng, Liping Xie, Ying Yu, Yong Ji, and Yi Han Copyright © 2016 Yan Tang et al. All rights reserved. Oxidative Stress in Metabolic Disorders: Pathogenesis, Prevention, and Therapeutics Mon, 01 Feb 2016 07:45:53 +0000 http://www.hindawi.com/journals/omcl/2016/9137629/ Umesh C. S. Yadav, Vibha Rani, Gagan Deep, Rakesh K. Singh, and Komaraiah Palle Copyright © 2016 Umesh C. S. Yadav et al. All rights reserved. Bioactive Peptides from Angelica sinensis Protein Hydrolyzate Delay Senescence in Caenorhabditis elegans through Antioxidant Activities Sun, 31 Jan 2016 16:53:44 +0000 http://www.hindawi.com/journals/omcl/2016/8956981/ Since excessive reactive oxygen species (ROS) is known to be associated with aging and age-related diseases, strategies modulating ROS level and antioxidant defense systems may contribute to the delay of senescence. Here we show that the protein hydrolyzate from Angelica sinensis was capable of increasing oxidative survival of the model animal Caenorhabditis elegans intoxicated by paraquat. The hydrolyzate was then fractionated by ultrafiltration, and the antioxidant fraction (<3 kDa) was purified by gel filtration to obtain the antioxidant A. sinensis peptides (AsiPeps), which were mostly composed of peptides with <20 amino acid residues. Further studies demonstrate that AsiPeps were able to reduce the endogenous ROS level, increase the activities of the antioxidant enzymes superoxide dismutase and catalase, and decrease the content of the lipid peroxidation product malondialdehyde in nematodes treated with paraquat or undergoing senescence. AsiPeps were also shown to reduce age pigments accumulation and extend lifespan but did not affect the food-intake behavior of the nematodes. Taken together, our results demonstrate that A. sinensis peptides (AsiPeps) are able to delay aging process in C. elegans through antioxidant activities independent of dietary restriction. Qiangqiang Wang, Yunxuan Huang, Chuixin Qin, Ming Liang, Xinliang Mao, Shuiming Li, Yongdong Zou, Weizhang Jia, Haifeng Li, Chung Wah Ma, and Zebo Huang Copyright © 2016 Qiangqiang Wang et al. All rights reserved. AP39, a Mitochondria-Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer’s Disease by Preserving Mitochondrial Function in APP/PS1 Mice and Neurons Sun, 31 Jan 2016 14:20:01 +0000 http://www.hindawi.com/journals/omcl/2016/8360738/ Increasing evidence suggests that mitochondrial functions are altered in AD and play an important role in AD pathogenesis. It has been established that H2S homeostasis is balanced in AD. The emerging mitochondrial roles of H2S include antioxidation, antiapoptosis, and the modulation of cellular bioenergetics. Here, using primary neurons from the well-characterized APP/PS1 transgenic mouse model, we studied the effects of AP39 (a newly synthesized mitochondrially targeted H2S donor) on mitochondrial function. AP39 increased intracellular H2S levels, mainly in mitochondrial regions. AP39 exerted dose-dependent effects on mitochondrial activity in APP/PS1 neurons, including increased cellular bioenergy metabolism and cell viability at low concentrations (25–100 nM) and decreased energy production and cell viability at a high concentration (250 nM). Furthermore, AP39 (100 nM) increased ATP levels, protected mitochondrial DNA, and decreased ROS generation. AP39 regulated mitochondrial dynamics, shifting from fission toward fusion. After 6 weeks, AP39 administration to APP/PS1 mice significantly ameliorated their spatial memory deficits in the Morris water maze and NORT and reduced Aβ deposition in their brains. Additionally, AP39 inhibited brain atrophy in APP/PS1 mice. Based on these results, AP39 was proposed as a promising drug candidate for AD treatment, and its anti-AD mechanism may involve protection against mitochondrial damage. Feng-li Zhao, Fang Fang, Pei-feng Qiao, Ning Yan, Dan Gao, and Yong Yan Copyright © 2016 Feng-li Zhao et al. All rights reserved. NADPH Oxidase: A Potential Target for Treatment of Stroke Sun, 31 Jan 2016 13:58:19 +0000 http://www.hindawi.com/journals/omcl/2016/5026984/ Stroke is the third leading cause of death in industrialized nations. Oxidative stress is involved in the pathogenesis of stroke, and excessive generation of reactive oxygen species (ROS) by mitochondria is thought to be the main cause of oxidative stress. NADPH oxidase (NOX) enzymes have recently been identified and studied as important producers of ROS in brain tissues after stroke. Several reports have shown that knockout or deletion of NOX exerts a neuroprotective effect in three major experimental stroke models. Recent studies also confirmed that NOX inhibitors ameliorate brain injury and improve neurological outcome after stroke. However, the physiological and pathophysiological roles of NOX enzymes in the central nervous system (CNS) are not known well. In this review, we provide a comprehensive summary of our current understanding about expression and physiological function of NOX enzymes in the CNS and its pathophysiological roles in the three major types of stroke: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Li Zhang, Jie Wu, Xiaochun Duan, Xiaodi Tian, Haitao Shen, Qing Sun, and Gang Chen Copyright © 2016 Li Zhang et al. All rights reserved. Nutrients, Microglia Aging, and Brain Aging Sun, 31 Jan 2016 12:56:11 +0000 http://www.hindawi.com/journals/omcl/2016/7498528/ As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging. Zhou Wu, Janchun Yu, Aiqin Zhu, and Hiroshi Nakanishi Copyright © 2016 Zhou Wu et al. All rights reserved. Oxidative Stress to Promote Cell Death or Survival Sun, 31 Jan 2016 07:29:06 +0000 http://www.hindawi.com/journals/omcl/2016/2054650/ Michela Battistelli, Manuela Malatesta, and Stefania Meschini Copyright © 2016 Michela Battistelli et al. All rights reserved. Oxidative DNA Damage Mediated by Intranuclear MMP Activity Is Associated with Neuronal Apoptosis in Ischemic Stroke Wed, 27 Jan 2016 14:27:18 +0000 http://www.hindawi.com/journals/omcl/2016/6927328/ Evidence of the pathological roles of matrix metalloproteinases (MMPs) in various neurological disorders has made them attractive therapeutic targets. MMPs disrupt the blood-brain barrier and cause neuronal death and neuroinflammation in acute cerebral ischemia and are critical for angiogenesis during recovery. However, some challenges have to be overcome before MMPs can be further validated as drug targets in stroke injury. Identifying in vivo substrates of MMPs should greatly improve our understanding of the mechanisms of ischemic injury and is critical for providing more precise drug targets. Recent works have uncovered nontraditional roles for MMPs in the cytosol and nucleus. These have shed light on intracellular targets and biological actions of MMPs, adding additional layers of complexity for therapeutic MMP inhibition. In this review, we discussed the recent advances made in understanding nuclear location of MMPs, their regulation of intranuclear sorting, and their intranuclear proteolytic activity and substrates. In particular, we highlighted the roles of intranuclear MMPs in oxidative DNA damage, neuronal apoptosis, and neuroinflammation at an early stage of stroke insult. These novel data point to new putative MMP-mediated intranuclear actions in stroke-induced pathological processes and may lead to novel approaches to treatment of stroke and other neurological diseases. Shihoko Kimura-Ohba and Yi Yang Copyright © 2016 Shihoko Kimura-Ohba and Yi Yang. All rights reserved. Biomarkers of Oxidative Stress in Experimental Models and Human Studies with Nutraceuticals: Measurement, Interpretation, and Significance Wed, 27 Jan 2016 11:10:52 +0000 http://www.hindawi.com/journals/omcl/2016/6159810/ Ilaria Peluso, Maura Palmery, Jara Pérez-Jiménez, and Gregor Drummen Copyright © 2016 Ilaria Peluso et al. All rights reserved. The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia Wed, 27 Jan 2016 07:34:35 +0000 http://www.hindawi.com/journals/omcl/2016/2492858/ Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation. M. H. Nielsen, H. Irvine, S. Vedel, B. Raungaard, H. Beck-Nielsen, and A. Handberg Copyright © 2016 M. H. Nielsen et al. All rights reserved. Preexposure to Olive Oil Polyphenols Extract Increases Oxidative Load and Improves Liver Mass Restoration after Hepatectomy in Mice via Stress-Sensitive Genes Tue, 26 Jan 2016 11:34:41 +0000 http://www.hindawi.com/journals/omcl/2016/9191407/ Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration—a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets -glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2. Jelena Marinić, Dalibor Broznić, and Čedomila Milin Copyright © 2016 Jelena Marinić et al. All rights reserved. Natural Products for the Prevention of Oxidative Stress-Related Diseases: Mechanisms and Strategies Tue, 26 Jan 2016 07:15:40 +0000 http://www.hindawi.com/journals/omcl/2016/4628502/ Wei Chen, Zhenquan Jia, Min-Hsiung Pan, and Pon Velayutham Anandh Babu Copyright © 2016 Wei Chen et al. All rights reserved. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies Sun, 24 Jan 2016 13:24:39 +0000 http://www.hindawi.com/journals/omcl/2016/2939087/ The main properties and biological effects of the antioxidant carnosine, the natural dipeptide β-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress. V. D. Prokopieva, E. G. Yarygina, N. A. Bokhan, and S. A. Ivanova Copyright © 2016 V. D. Prokopieva et al. All rights reserved. Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More Sun, 24 Jan 2016 09:53:16 +0000 http://www.hindawi.com/journals/omcl/2016/2986796/ Increasing interest has recently focused on determining whether several natural compounds, collectively referred to as nutraceuticals, may exert neuroprotective actions in the developing, adult, and aging nervous system. Quercetin, a polyphenol widely present in nature, has received the most attention in this regard. Several studies in vitro, in experimental animals and in humans, have provided supportive evidence for neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress. Two such pathways include the induction of Nrf2-ARE and induction of the antioxidant/anti-inflammatory enzyme paraoxonase 2 (PON2). In addition, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection. Lucio G. Costa, Jacqueline M. Garrick, Pamela J. Roquè, and Claudia Pellacani Copyright © 2016 Lucio G. Costa et al. All rights reserved. Decavanadate Toxicology and Pharmacological Activities: V10 or V1, Both or None? Thu, 21 Jan 2016 13:20:46 +0000 http://www.hindawi.com/journals/omcl/2016/6103457/ This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mitochondrial membrane depolarization is a key event in decavanadate induction of necrotic cardiomyocytes death. Furthermore, only decavanadate species and not V1 potently inhibited myosin ATPase activity stimulated by actin (IC50 = 0.75 μM) whereas exhibiting lower inhibition activities for Ca2+-ATPase activity (15 μM) and actin polymerization (17 μM). Because both calcium pump and actin decavanadate interactions lead to its stabilization, it is likely that V10 interacts at specific locations with these proteins that protect against hydrolysis but, on the other hand, it may induce V10 reduction to oxidovanadium(IV). Putting it all together, it is suggested that the pharmacological applications of V10 species and compounds whose mechanism of action is still to be clarified might involve besides V10 and V1 also vanadium(IV) species. M. Aureliano Copyright © 2016 M. Aureliano. All rights reserved. Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.) Thu, 21 Jan 2016 07:21:50 +0000 http://www.hindawi.com/journals/omcl/2016/8915729/ Grapefruit (Citrus paradisi Macf.) is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C–60°C) and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45°C) exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1–0.25 mg/mL. Our data suggest that grapefruit (Citrus paradisi Macf.) peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies. Lucia Castro-Vazquez, María Elena Alañón, Virginia Rodríguez-Robledo, María Soledad Pérez-Coello, Isidro Hermosín-Gutierrez, María Consuelo Díaz-Maroto, Joaquín Jordán, María Francisca Galindo, and María del Mar Arroyo-Jiménez Copyright © 2016 Lucia Castro-Vazquez et al. All rights reserved. Beneficial Effects of Physical Exercise on Functional Capacity and Skeletal Muscle Oxidative Stress in Rats with Aortic Stenosis-Induced Heart Failure Wed, 20 Jan 2016 15:00:02 +0000 http://www.hindawi.com/journals/omcl/2016/8695716/ Objective. We evaluated the influence of exercise on functional capacity, cardiac remodeling, and skeletal muscle oxidative stress, MAPK, and NF-κB pathway in rats with aortic stenosis- (AS-) induced heart failure (HF). Methods and Results. Eighteen weeks after AS induction, rats were assigned into sedentary control (C-Sed), exercised control (C-Ex), sedentary AS (AS-Sed), and exercised AS (AS-Ex) groups. Exercise was performed on treadmill for eight weeks. Statistical analyses were performed with Goodman and ANOVA or Mann-Whitney. HF features frequency and mortality did not differ between AS groups. Exercise improved functional capacity, assessed by maximal exercise test on treadmill, without changing echocardiographic parameters. Soleus cross-sectional areas did not differ between groups. Lipid hydroperoxide concentration was higher in AS-Sed than C-Sed and AS-Ex. Activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase was changed in AS-Sed and restored in AS-Ex. NADPH oxidase activity and gene expression of its subunits did not differ between AS groups. Total ROS generation was lower in AS-Ex than C-Ex. Exercise modulated MAPK in AS-Ex and did not change NF-κB pathway proteins. Conclusion. Exercise improves functional capacity in rats with AS-induced HF regardless of echocardiographic parameter changes. In soleus, exercise reduces oxidative stress, preserves antioxidant enzyme activity, and modulates MAPK expression. Mariana Janini Gomes, Paula Felippe Martinez, Dijon Henrique Salomé Campos, Luana Urbano Pagan, Camila Bonomo, Aline Regina Ruiz Lima, Ricardo Luiz Damatto, Marcelo D. M. Cezar, Felipe Cezar Damatto, Camila Moreno Rosa, Camila Marchiolli Garcia, David Rafael Abreu Reyes, Ana Angélica Henrique Fernandes, Denise Castro Fernandes, Francisco Rafael Laurindo, Katashi Okoshi, and Marina Politi Okoshi Copyright © 2016 Mariana Janini Gomes et al. All rights reserved. TGF-β and Hypoxia/Reoxygenation Promote Radioresistance of A549 Lung Cancer Cells through Activation of Nrf2 and EGFR Wed, 20 Jan 2016 11:57:17 +0000 http://www.hindawi.com/journals/omcl/2016/6823471/ Although many studies have examined the roles of hypoxia and transforming growth factor- (TGF-) β separately in the tumor microenvironment, the effects of simultaneous treatment with hypoxia/reoxygenation and TGF-β on tumor malignancy are unclear. Here, we investigated the effects of redox signaling and oncogenes on cell proliferation and radioresistance in A549 human lung cancer cells in the presence of TGF-β under hypoxia/reoxygenation conditions. Combined treatment with TGF-β and hypoxia activated epidermal growth factor receptor (EGFR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a redox-sensitive transcription factor. Interestingly, Nrf2 knockdown suppressed the effects of combined treatment on EGFR phosphorylation. In addition, blockade of EGFR signaling also suppressed induction of Nrf2 following combined treatment with hypoxia and TGF-β, indicating that the combined treatment induced positive crosstalk between Nrf2 and EGFR. TGF-β and hypoxia/reoxygenation increased the accumulation of reactive oxygen species (ROS), while treatment with N-acetyl-L-cysteine abolished the activation of Nrf2 and EGFR. Treatment with TGF-β under hypoxic conditions increased the proliferation of A549 cells compared with that after vehicle treatment. Moreover, cells treated with the combined treatment exhibited resistance to ionizing radiation (IR), and knockdown of Nrf2 increased IR-induced cell death under these conditions. Thus, taken together, our findings suggested that TGF-β and hypoxia/reoxygenation promoted tumor progression and radioresistance of A549 cells through ROS-mediated activation of Nrf2 and EGFR. Sae-lo-oom Lee, Hwani Ryu, A-rang Son, Bitna Seo, Jooyoung Kim, Seung-Youn Jung, Jie-Young Song, Sang-Gu Hwang, and Jiyeon Ahn Copyright © 2016 Sae-lo-oom Lee et al. All rights reserved. Epithelial Electrolyte Transport Physiology and the Gasotransmitter Hydrogen Sulfide Wed, 20 Jan 2016 11:33:45 +0000 http://www.hindawi.com/journals/omcl/2016/4723416/ Hydrogen sulfide (H2S) is a well-known environmental chemical threat with an unpleasant smell of rotten eggs. Aside from the established toxic effects of high-dose H2S, research over the past decade revealed that cells endogenously produce small amounts of H2S with physiological functions. H2S has therefore been classified as a “gasotransmitter.” A major challenge for cells and tissues is the maintenance of low physiological concentrations of H2S in order to prevent potential toxicity. Epithelia of the respiratory and gastrointestinal tract are especially faced with this problem, since these barriers are predominantly exposed to exogenous H2S from environmental sources or sulfur-metabolising microbiota. In this paper, we review the cellular mechanisms by which epithelial cells maintain physiological, endogenous H2S concentrations. Furthermore, we suggest a concept by which epithelia use their electrolyte and liquid transport machinery as defence mechanisms in order to eliminate exogenous sources for potentially harmful H2S concentrations. Ervice Pouokam and Mike Althaus Copyright © 2016 Ervice Pouokam and Mike Althaus. All rights reserved. Memory Deficit Recovery after Chronic Vanadium Exposure in Mice Tue, 19 Jan 2016 18:17:14 +0000 http://www.hindawi.com/journals/omcl/2016/4860582/ Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal. Oluwabusayo Folarin, Funmilayo Olopade, Silas Onwuka, and James Olopade Copyright © 2016 Oluwabusayo Folarin et al. All rights reserved. Antioxidant and Antifatigue Properties of the Aqueous Extract of Moringa oleifera in Rats Subjected to Forced Swimming Endurance Test Tue, 19 Jan 2016 18:16:18 +0000 http://www.hindawi.com/journals/omcl/2016/3517824/ The effects of the aqueous extract of Moringa oleifera on swimming performance and related biochemical parameters were investigated in male Wistar rats (130–132 g). Four groups of rats (16 per group) were fed a standard laboratory diet and given distilled water, 100, 200, or 400 mg/kg of extract, respectively, for 28 days. On day 28, 8 rats from each group were subjected to the forced swimming test with tail load (10% of body weight). The remaining 8 rats per group were subjected to the 90-minute free swim. Maximum swimming time, glycemia, lactamia, uremia, triglyceridemia, hepatic and muscle glycogen, hematological parameters, and oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, and malondialdehyde) were measured. Results. M. oleifera extract increased maximum swimming time, blood hemoglobin, blood glucose, and hepatic and muscle glycogen reserves. The extract also increased the activity of antioxidant enzymes and decreased the blood concentrations of malondialdehyde. Furthermore, it decreased blood concentrations of lactate, triglycerides, and urea. In conclusion, the antifatigue properties of M. oleifera extract are demonstrated by its ability to improve body energy stores and tissue antioxidant capacity and to reduce the tissue build-up of lactic acid. Bonoy Lamou, Germain Sotoing Taiwe, André Hamadou, Abene, Justin Houlray, Mahamat Mey Atour, and Paul Vernyuy Tan Copyright © 2016 Bonoy Lamou et al. All rights reserved. Skin Antiageing and Systemic Redox Effects of Supplementation with Marine Collagen Peptides and Plant-Derived Antioxidants: A Single-Blind Case-Control Clinical Study Tue, 19 Jan 2016 13:46:26 +0000 http://www.hindawi.com/journals/omcl/2016/4389410/ Recently, development and research of nutraceuticals based on marine collagen peptides (MCPs) have been growing due to their high homology with human collagens, safety, bioavailability through gut, and numerous bioactivities. The major concern regarding safety of MCPs intake relates to increased risk of oxidative stress connected with collagen synthesis (likewise in fibrosis) and to ROS production by MCPs-stimulated phagocytes. In this clinical-laboratory study, fish skin MCPs combined with plant-derived skin-targeting antioxidants (AO) (coenzyme Q10 + grape-skin extract + luteolin + selenium) were administered to volunteers (). Skin properties (moisture, elasticity, sebum production, and biological age) and ultrasonic markers (epidermal/dermal thickness and acoustic density) were measured thrice (2 months before treatment and before and after cessation of 2-month oral intake). The supplementation remarkably improved skin elasticity, sebum production, and dermal ultrasonic markers. Metabolic data showed significant increase of plasma hydroxyproline and ATP storage in erythrocytes. Redox parameters, GSH/coenzyme Q10 content, and GPx/GST activities were unchanged, while NO and MDA were moderately increased within, however, normal range of values. Conclusions. A combination of MCPs with skin-targeting AOs could be effective and safe supplement to improve skin properties without risk of oxidative damage. Chiara De Luca, Elena V. Mikhal’chik, Maxim V. Suprun, Michael Papacharalambous, Arseniy I. Truhanov, and Liudmila G. Korkina Copyright © 2016 Chiara De Luca et al. All rights reserved.