Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. The Protective Effects of Curcumin on Experimental Acute Liver Lesion Induced by Intestinal Ischemia-Reperfusion through Inhibiting the Pathway of NF-κB in a Rat Model Wed, 20 Aug 2014 08:33:22 +0000 http://www.hindawi.com/journals/omcl/2014/191624/ Objective. In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R), which induces an acute liver lesion. Methods. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline) was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) expression. Conclusion. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway. Zhe Fan, Huirong Jing, Jihong Yao, Yang Li, Xiaowei Hu, Huizhu Shao, Gang Shen, Jiyong Pan, Fuwen Luo, and Xiaofeng Tian Copyright © 2014 Zhe Fan et al. All rights reserved. Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy Wed, 20 Aug 2014 07:35:33 +0000 http://www.hindawi.com/journals/omcl/2014/780179/ Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ), an important component in Alzheimer’s disease (AD) pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβ import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP) formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed. Pasquale Picone, Domenico Nuzzo, Luca Caruana, Valeria Scafidi, and Marta Di Carlo Copyright © 2014 Pasquale Picone et al. All rights reserved. Oxidative Stress-Mediated Aging during the Fetal and Perinatal Periods Mon, 18 Aug 2014 12:06:41 +0000 http://www.hindawi.com/journals/omcl/2014/358375/ Oxidative stress is worldwide recognized as a fundamental component of the aging, a process that begins before birth. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress is caused by an imbalance between the production of free radicals and the ability of antioxidant system to detoxify them. Oxidative stress can occur early in pregnancy and continue in the postnatal period; this damage is implicated in the pathophysiology of pregnancy-related disorders, including recurrent pregnancy loss, preeclampsia and preterm premature rupture of membranes. Moreover, diseases of the neonatal period such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia are related to free radical damage. The specific contribution of oxidative stress to the pathogenesis and progression of these neonatal diseases is only partially understood. This review summarizes what is known about the role of oxidative stress in pregnancy and in the pathogenesis of common disorders of the newborn, as a component of the early aging process. Lucia Marseglia, Gabriella D’Angelo, Sara Manti, Teresa Arrigo, Ignazio Barberi, Russel J. Reiter, and Eloisa Gitto Copyright © 2014 Lucia Marseglia et al. All rights reserved. Effect of Staurosporine in the Morphology and Viability of Cerebellar Astrocytes: Role of Reactive Oxygen Species and NADPH Oxidase Sun, 17 Aug 2014 11:08:36 +0000 http://www.hindawi.com/journals/omcl/2014/678371/ Cell death implies morphological changes that may contribute to the progression of this process. In astrocytes, the mechanisms involving the cytoskeletal changes during cell death are not well explored. Although NADPH oxidase (NOX) has been described as being a critical factor in the production of ROS, not much information is available about the participation of NOX-derived ROS in the cell death of astrocytes and their role in the alterations of the cytoskeleton during the death of astrocytes. In this study, we have evaluated the participation of ROS in the death of cultured cerebellar astrocytes using staurosporine (St) as death inductor. We found that astrocytes express NOX1, NOX2, and NOX4. Also, St induced an early ROS production and NOX activation that participate in the death of astrocytes. These findings suggest that ROS produced by St is generated through NOX1 and NOX4. Finally, we showed that the reorganization of tubulin and actin induced by St is ROS independent and that St did not change the level of expression of these cytoskeletal proteins. We conclude that ROS produced by a NOX is required for cell death in astrocytes, but not for the morphological alterations induced by St. Mauricio Olguín-Albuerne, Guadalupe Domínguez, and Julio Morán Copyright © 2014 Mauricio Olguín-Albuerne et al. All rights reserved. Short-Term Diet and Moderate Exercise in Young Overweight Men Modulate Cardiocyte and Hepatocarcinoma Survival by Oxidative Stress Wed, 13 Aug 2014 10:53:11 +0000 http://www.hindawi.com/journals/omcl/2014/131024/ The present study was designed to evaluate the effects of diet lifestyle on extending lifespan and reducing liver cancer risk. Young overweight men , without metabolic syndrome, were placed in a 3-week residential program on a low-fat diet and moderate aerobic exercise. In each subject, pre- and postintervention fasting blood were collected for evaluating levels of serum lipids, and oxidative stress markers. Using subject sera and cardiomyocyte (H9C2) culture systems, we measured heat shock protein 27 and 90 expression, lipid accumulation, and oxidative stress marker levels. After 3-weeks of diet, significant reductions in body mass index, serum lipids and lipid ratios, and oxidative markers were recorded. In vitro, we observed that the addition of postintervention sera increased H9C2 cell number and reduced HSP27 and 90 expression, mitochondrial superoxide anion, and lipid accumulation with a parallel increase in nitric oxide (NO) production (all ). At the same time, postintervention sera decreased human liver hepatocellular carcinoma cell line (HepG-2) proliferation, lipid accumulation, oxidative stress, and extracellular-signal-regulated kinases (ERK1/2) activity. Lifestyle modification in young overweight men, without metabolic syndrome, could ameliorate cardiocyte survival and reduce hepatocellular carcinoma cell proliferation. Marcellino Monda, Giovanni Messina, Ilaria Scognamiglio, Angela Lombardi, Giuseppe A. Martin, Pasquale Sperlongano, Marina Porcelli, Michele Caraglia, and Paola Stiuso Copyright © 2014 Marcellino Monda et al. All rights reserved. Anticonvulsant and Antioxidant Effects of Tilia americana var. mexicana and Flavonoids Constituents in the Pentylenetetrazole-Induced Seizures Wed, 13 Aug 2014 05:11:47 +0000 http://www.hindawi.com/journals/omcl/2014/329172/ Tilia genus is commonly used around the world for its central nervous system properties; it is prepared as tea and used as tranquilizing, anticonvulsant, and analgesic. In this study, anticonvulsant activity of the Tilia americana var. mexicana inflorescences and leaves was investigated by evaluating organic and aqueous extracts (100, 300, and 600 mg/kg, i.p.) and some flavonoids in the pentylenetetrazole-induced seizures in mice. Moreover, antioxidant effect of these extracts and flavonoids was examined in an in vitro study by using spectrophotometric technique. Significant activity was observed in the methanol extract from inflorescences. An HPLC analysis of the methanol extract from inflorescences and leaves of Tilia allowed demonstrating the respective presence of some partial responsible flavonoid constituents: quercetin (20.09 ± 1.20 μg/mg and 3.39 ± 0.10 μg/mg), rutin (3.52 ± 0.21 μg/mg and 8.94 ± 0.45 μg/mg), and isoquercitrin (1.74 ± 0.01 μg/mg and 1.24 ± 0.13 μg/mg). In addition, significant but different antioxidant properties were obtained among the flavonoids and the extracts investigated. Our results provide evidence of the anticonvulsant activity of Tilia reinforcing its utility for central nervous system diseases whose mechanism of action might involve partial antioxidant effects due to the presence of flavonoids. Noemí Cárdenas-Rodríguez, María Eva González-Trujano, Eva Aguirre-Hernández, Matilde Ruíz-García, Aristides Sampieri III, Elvia Coballase-Urrutia, and Liliana Carmona-Aparicio Copyright © 2014 Noemí Cárdenas-Rodríguez et al. All rights reserved. Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation Tue, 12 Aug 2014 11:44:59 +0000 http://www.hindawi.com/journals/omcl/2014/302528/ The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis () treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score). Lenka Borska, Ctirad Andrys, Jan Krejsek, Vladimir Palicka, Marcela Chmelarova, Kvetoslava Hamakova, Jan Kremlacek, and Zdenek Fiala Copyright © 2014 Lenka Borska et al. All rights reserved. Propofol Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-Alpha Expression and Myocardial Depression through Decreasing the Generation of Superoxide Anion in Cardiomyocytes Mon, 11 Aug 2014 11:21:31 +0000 http://www.hindawi.com/journals/omcl/2014/157376/ TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis. Jing Tang, Ji-Jie Hu, Chun-Hua Lu, Jia-Ni Liang, Jin-Fang Xiao, You-Tan Liu, Chun-Shui Lin, and Zai-Sheng Qin Copyright © 2014 Jing Tang et al. All rights reserved. Oxidative Stress: Implications for the Development of Diabetic Retinopathy and Antioxidant Therapeutic Perspectives Sun, 10 Aug 2014 12:11:17 +0000 http://www.hindawi.com/journals/omcl/2014/752387/ In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR. Ying Wu, Luosheng Tang, and Baihua Chen Copyright © 2014 Ying Wu et al. All rights reserved. Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies Sun, 10 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/703848/ Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels. Franklin F. F. Nóbrega, Mirian G. S. S. Salvadori, Cintia J. Masson, Carlos F. Mello, Tiago S. Nascimento, José H. Leal-Cardoso, Damião P. de Sousa, and Reinaldo N. Almeida Copyright © 2014 Franklin F. F. Nóbrega et al. All rights reserved. Epicatechin and Catechin Modulate Endothelial Activation Induced by Platelets of Patients with Peripheral Artery Disease Thu, 07 Aug 2014 07:18:16 +0000 http://www.hindawi.com/journals/omcl/2014/691015/ Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that epicatechin plus catechin reduces endothelial activation induced by activated platelets. R. Carnevale, L. Loffredo, C. Nocella, S. Bartimoccia, T. Bucci, E. De Falco, M. Peruzzi, I. Chimenti, G. Biondi-Zoccai, P. Pignatelli, F. Violi, and G. Frati Copyright © 2014 R. Carnevale et al. All rights reserved. The Effects of Sesquiterpenes-Rich Extract of Alpinia oxyphylla Miq. on Amyloid-β-Induced Cognitive Impairment and Neuronal Abnormalities in the Cortex and Hippocampus of Mice Thu, 07 Aug 2014 06:57:10 +0000 http://www.hindawi.com/journals/omcl/2014/451802/ As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ1−42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions. Shao-Huai Shi, Xu Zhao, Bing Liu, Huan Li, Ai-Jing Liu, Bo Wu, Kai-Shun Bi, and Ying Jia Copyright © 2014 Shao-Huai Shi et al. All rights reserved. Deletion of Metallothionein Exacerbates Intermittent Hypoxia-Induced Oxidative and Inflammatory Injury in Aorta Wed, 06 Aug 2014 07:27:52 +0000 http://www.hindawi.com/journals/omcl/2014/141053/ The present study was to explore the effect of metallothionein (MT) on intermittent hypoxia (IH) induced aortic pathogenic changes. Markers of oxidative damages, inflammation, and vascular remodeling were observed by immunohistochemical staining after 3 days and 1, 3, and 8 weeks after IH exposures. Endogenous MT was induced after 3 days of IH but was significantly decreased after 8 weeks of IH. Compared with the wild-type mice, MT knock-out mice exhibited earlier and more severe pathogenic changes of oxidative damages, inflammatory responses, and cellular apoptosis, as indicated by the significant accumulation of collagen, increased levels of connective tissue growth factor, transforming growth factor , tumor necrosis factor-alpha, vascular cell adhesion molecule 1,3-nitrotyrosine, and 4-hydroxy-2-nonenal in the aorta. These findings suggested that chronic IH may lead to aortic damages characterized by oxidative stress and inflammation, and MT may play a pivotal role in the above pathogenesis process. Shanshan Zhou, Yonggang Wang, Yi Tan, Xiaohong Cai, Lu Cai, Jun Cai, and Yang Zheng Copyright © 2014 Shanshan Zhou et al. All rights reserved. Nitric Oxide-Related Oxidative Stress and Redox Status in Health and Disease Wed, 23 Jul 2014 10:13:00 +0000 http://www.hindawi.com/journals/omcl/2014/129651/ Darko Modun, Daniela Giustarini, and Dimitrios Tsikas Copyright © 2014 Darko Modun et al. All rights reserved. Subanesthetic Isoflurane Reduces Zymosan-Induced Inflammation in Murine Kupffer Cells by Inhibiting ROS-Activated p38 MAPK/NF-κB Signaling Wed, 23 Jul 2014 07:28:44 +0000 http://www.hindawi.com/journals/omcl/2014/851692/ Volatile anesthetic isoflurane (ISO) has immunomodulatory effects. The fungal component zymosan (ZY) induces inflammation through toll-like receptor 2 or dectin-1 signaling. We investigated the molecular actions of subanesthetic (0.7%) ISO against ZY-induced inflammatory activation in murine Kupffer cells (KCs), which are known as the resident macrophages within the liver. We observed that ISO reduced ZY-induced cyclooxygenase 2 upregulation and prostaglandin E2 release, as determined by western blot and radioimmunoassay, respectively. ISO also reduced the production of tumor necrosis factor-α, interleukin-1β, IL-6, high-mobility group box-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 as assessed by enzyme-linked immunosorbent assays. ISO blocked the ZY-induced nuclear translocation and DNA-binding activity of nuclear factor- (NF)-κB p65. Moreover, ISO attenuated ZY-induced p38 mitogen-activated protein kinase (MAPK) activation partly by scavenging reactive oxygen species (ROS); the interregulation that ROS activated p38 MAPK followed by NF-κB activation was crucial for the ZY-induced inflammatory responses in KCs. An in vivo study by peritoneal injection of ZY into BALB/C mice confirmed the anti-inflammatory properties of 0.7% ISO against ZY in KCs. These results suggest that ISO ameliorates ZY-induced inflammatory responses in murine KCs by inhibiting the interconnected ROS/p38 MAPK/NF-κB signaling pathways. Hui Wang, Lei Wang, Nan-lin Li, Jun-tang Li, Feng Yu, Ya-li Zhao, Ling Wang, Jun Yi, Ling Wang, Jie-fang Bian, Jiang-hao Chen, Shi-fang Yuan, Ting Wang, Yong-gang Lv, Ning-ning Liu, Xiao-shan Zhu, Rui Ling, and Jun Yun Copyright © 2014 Hui Wang et al. All rights reserved. Decitabine and SAHA-Induced Apoptosis Is Accompanied by Survivin Downregulation and Potentiated by ATRA in p53-Deficient Cells Mon, 21 Jul 2014 11:19:42 +0000 http://www.hindawi.com/journals/omcl/2014/165303/ While p53-dependent apoptosis is triggered by combination of methyltransferase inhibitor decitabine (DAC) and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in leukemic cell line CML-T1, reactive oxygen species (ROS) generation as well as survivin and Bcl-2 deregulation participated in DAC + SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of survivin expression level is accompanied by its delocalization from centromere-related position in mitotic cells suggesting that both antiapoptotic and cell cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of subtoxic concentration of all-trans-retinoic acid (ATRA) increases the efficiency of DAC + SAHA combination on viability, apoptosis induction, and ROS generation in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA combination. Therefore, combination of ATRA with DAC and SAHA represents promising tool for therapy of leukemic disease with nonfunctional p53 signalization. Barbora Brodská, Petra Otevřelová, and Aleš Holoubek Copyright © 2014 Barbora Brodská et al. All rights reserved. The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution Sun, 20 Jul 2014 07:30:20 +0000 http://www.hindawi.com/journals/omcl/2014/671539/ Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example, -carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants. Borut Poljšak and Rok Fink Copyright © 2014 Borut Poljšak and Rok Fink. All rights reserved. Oxidative Stress and Metabolic Pathologies: From an Adipocentric Point of View Sun, 20 Jul 2014 06:10:03 +0000 http://www.hindawi.com/journals/omcl/2014/908539/ Oxidative stress plays a pathological role in the development of various diseases including diabetes, atherosclerosis, or cancer. Systemic oxidative stress results from an imbalance between oxidants derivatives production and antioxidants defenses. Reactive oxygen species (ROS) are generally considered to be detrimental for health. However, evidences have been provided that they can act as second messengers in adaptative responses to stress. Obesity represents a major risk factor for deleterious associated pathologies such as type 2 diabetes, liver, and coronary heart diseases. Many evidences regarding obesity-induced oxidative stress accumulated over the past few years based on established correlations of biomarkers or end-products of free-radical-mediated oxidative stress with body mass index. The hypothesis that oxidative stress plays a significant role in the development of metabolic disorders, especially insulin-resistance state, is supported by several studies where treatments reducing ROS production reverse metabolic alterations, notably through improvement of insulin sensitivity, hyperlipidemia, or hepatic steatosis. In this review, we will develop the mechanistic links between oxidative stress generated by adipose tissue in the context of obesity and its impact on metabolic complications development. We will also attempt to discuss potential therapeutic approaches targeting obesity-associated oxidative stress in order to prevent associated-metabolic complications. Soazig Le Lay, Gilles Simard, Maria Carmen Martinez, and Ramaroson Andriantsitohaina Copyright © 2014 Soazig Le Lay et al. All rights reserved. A Review on Hemeoxygenase-2: Focus on Cellular Protection and Oxygen Response Thu, 17 Jul 2014 12:27:26 +0000 http://www.hindawi.com/journals/omcl/2014/604981/ Hemeoxygenase (HO) system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia. Jorge Muñoz-Sánchez and María Elena Chánez-Cárdenas Copyright © 2014 Jorge Muñoz-Sánchez and María Elena Chánez-Cárdenas. All rights reserved. Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase Thu, 17 Jul 2014 12:25:03 +0000 http://www.hindawi.com/journals/omcl/2014/893516/ Background. Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA. Methods. The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression. Results. HT22 cells exposed to H2O2 demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA. Conclusion. Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells. Ji Jia, Lei Ma, Mingchun Wu, Lei Zhang, Xiajing Zhang, Qian Zhai, Tao Jiang, Qiang Wang, and Lize Xiong Copyright © 2014 Ji Jia et al. All rights reserved. Multimarker Screening of Oxidative Stress in Aging Wed, 16 Jul 2014 08:54:18 +0000 http://www.hindawi.com/journals/omcl/2014/562860/ Aging is a complex process of organism decline in physiological functions. There is no clear theory explaining this phenomenon, but the most accepted one is the oxidative stress theory of aging. Biomarkers of oxidative stress, substances, which are formed during oxidative damage of phospholipids, proteins, and nucleic acids, are present in body fluids of diseased people as well as the healthy ones (in a physiological concentration). 8-iso prostaglandin F2α is the most prominent biomarker of phospholipid oxidative damage, o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine are biomarkers of protein oxidative damage, and 8-hydroxy-2′-deoxyguanosine and 8-hydroxyguanosine are biomarkers of oxidative damage of nucleic acids. It is thought that the concentration of biomarkers increases as the age of people increases. However, the concentration of biomarkers in body fluids is very low and, therefore, it is necessary to use a sensitive analytical method. A combination of HPLC and MS was chosen to determine biomarker concentration in three groups of healthy people of a different age (twenty, forty, and sixty years) in order to find a difference among the groups. Kamila Syslová, Adéla Böhmová, Miloš Mikoška, Marek Kuzma, Daniela Pelclová, and Petr Kačer Copyright © 2014 Kamila Syslová et al. All rights reserved. New Insights into the Role of Mitochondrial Dynamics and Autophagy during Oxidative Stress and Aging in the Heart Tue, 15 Jul 2014 07:11:14 +0000 http://www.hindawi.com/journals/omcl/2014/210934/ The heart is highly sensitive to the aging process. In the elderly, the heart tends to become hypertrophic and fibrotic. Stiffness increases with ensuing systolic and diastolic dysfunction. Aging also affects the cardiac response to stress. At the molecular level, the aging process is associated with accumulation of damaged proteins and organelles, partially due to defects in protein quality control systems. The accumulation of dysfunctional and abnormal mitochondria is an important pathophysiological feature of the aging process, which is associated with excessive production of reactive oxygen species. Mitochondrial fusion and fission and mitochondrial autophagy are crucial mechanisms for maintaining mitochondrial function and preserving energy production. In particular, mitochondrial fission allows for selective segregation of damaged mitochondria, which are afterward eliminated by autophagy. Unfortunately, recent evidence indicates that mitochondrial dynamics and autophagy are progressively impaired over time, contributing to the aging process. This suggests that restoration of these mechanisms could delay organ senescence and prevent age-associated cardiac diseases. Here, we discuss the current understanding of the close relationship between mitochondrial dynamics, mitophagy, oxidative stress, and aging, with a particular focus on the heart. Yoshiyuki Ikeda, Sebastiano Sciarretta, Narayani Nagarajan, Speranza Rubattu, Massimo Volpe, Giacomo Frati, and Junichi Sadoshima Copyright © 2014 Yoshiyuki Ikeda et al. All rights reserved. Expression of Senescence-Associated microRNAs and Target Genes in Cellular Aging and Modulation by Tocotrienol-Rich Fraction Mon, 14 Jul 2014 13:42:46 +0000 http://www.hindawi.com/journals/omcl/2014/725929/ Emerging evidences highlight the implication of microRNAs as a posttranscriptional regulator in aging. Several senescence-associated microRNAs (SA-miRNAs) are found to be differentially expressed during cellular senescence. However, the role of dietary compounds on SA-miRNAs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on SA-miRNAs (miR-20a, miR-24, miR-34a, miR-106a, and miR-449a) and established target genes of miR-34a (CCND1, CDK4, and SIRT1) during replicative senescence of human diploid fibroblasts (HDFs). Primary cultures of HDFs at young and senescent were incubated with TRF at 0.5 mg/mL. Taqman microRNA assay showed significant upregulation of miR-24 and miR-34a and downregulation of miR-20a and miR-449a in senescent HDFs (). TRF reduced miR-34a expression in senescent HDFs and increased miR-20a expression in young HDFs and increased miR-449a expression in both young and senescent HDFs. Our results also demonstrated that ectopic expression of miR-34a reduced the expression of CDK4 significantly (). TRF inhibited miR-34a expression thus relieved its inhibition on CDK4 gene expression. No significant change was observed on the expression of CCND1, SIRT1, and miR-34a upstream transcriptional regulator, TP53. In conclusion tocotrienol-rich fraction prevented cellular senescence of human diploid fibroblasts via modulation of SA-miRNAs and target genes expression. Sharon Gwee Sian Khee, Yasmin Anum Mohd Yusof, and Suzana Makpol Copyright © 2014 Sharon Gwee Sian Khee et al. All rights reserved. The Beneficial Effect of Melatonin in Brain Endothelial Cells against Oxygen-Glucose Deprivation Followed by Reperfusion-Induced Injury Mon, 14 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/639531/ Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury. Juhyun Song, So Mang Kang, Won Taek Lee, Kyung Ah Park, Kyoung Min Lee, and Jong Eun Lee Copyright © 2014 Juhyun Song et al. All rights reserved. Vitamin A Supplementation Alleviates Extrahepatic Cholestasis Liver Injury through Nrf2 Activation Wed, 09 Jul 2014 08:53:03 +0000 http://www.hindawi.com/journals/omcl/2014/273692/ Aim. To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats. Methods. Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays. Results. Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1. Conclusion. Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats. Guiyang Wang, Peng Xiu, Fu Li, Cheng Xin, and Kewei Li Copyright © 2014 Guiyang Wang et al. All rights reserved. Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis Mon, 07 Jul 2014 09:06:02 +0000 http://www.hindawi.com/journals/omcl/2014/726590/ Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis. Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−). Bone microarchitecture was analyzed by μCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123. Results. Sham-operated or ovariectomized Nrf2−/− mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/− mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro. Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture. Lidia Ibáñez, María Luisa Ferrándiz, Rita Brines, David Guede, Antonio Cuadrado, and Maria José Alcaraz Copyright © 2014 Lidia Ibáñez et al. All rights reserved. Novel Functional Changes during Podocyte Differentiation: Increase of Oxidative Resistance and H-Ferritin Expression Sun, 06 Jul 2014 08:24:53 +0000 http://www.hindawi.com/journals/omcl/2014/976394/ Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H2O2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well. Emese Bányai, Enikő Balogh, Miklós Fagyas, Paolo Arosio, Zoltán Hendrik, Gábor Király, Gábor Nagy, Bence Tánczos, István Pócsi, György Balla, József Balla, Gáspár Bánfalvi, and Viktória Jeney Copyright © 2014 Emese Bányai et al. All rights reserved. Vitamin E in Sarcopenia: Current Evidences on Its Role in Prevention and Treatment Sun, 06 Jul 2014 07:14:48 +0000 http://www.hindawi.com/journals/omcl/2014/914853/ Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS) can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies. Shy Cian Khor, Norwahidah Abdul Karim, Wan Zurinah Wan Ngah, Yasmin Anum Mohd Yusof, and Suzana Makpol Copyright © 2014 Shy Cian Khor et al. All rights reserved. Oxidative Stresses and Mitochondrial Dysfunction in Age-Related Hearing Loss Thu, 03 Jul 2014 12:13:15 +0000 http://www.hindawi.com/journals/omcl/2014/582849/ Age-related hearing loss (ARHL), the progressive loss of hearing associated with aging, is the most common sensory disorder in the elderly population. The pathology of ARHL includes the hair cells of the organ of Corti, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Mitochondria play a crucial role in the induction of intrinsic apoptosis in cochlear cells. ARHL can be prevented in laboratory animals by certain interventions, such as caloric restriction and supplementation with antioxidants. In this review, we will focus on previous research concerning the role of the oxidative stress and mitochondrial dysfunction in the pathology of ARHL in both animal models and humans and introduce concepts that have recently emerged regarding the mechanisms of the development of ARHL. Chisato Fujimoto and Tatsuya Yamasoba Copyright © 2014 Chisato Fujimoto and Tatsuya Yamasoba. All rights reserved. Atorvastatin Represses the Angiotensin 2-Induced Oxidative Stress and Inflammatory Response in Dendritic Cells via the PI3K/Akt/Nrf 2 Pathway Thu, 03 Jul 2014 07:04:45 +0000 http://www.hindawi.com/journals/omcl/2014/148798/ Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play a complex role in both the initiation and progression of atherosclerosis. We tested the hypothesis that the anti-inflammatory and antioxidant effects of atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein kinase B/transcription factor nuclear factor-erythroid 2-related factor 2 (PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the inflammatory and oxidative stress responses. This study showed that angiotensin 2 (Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86 expression, and increased the secretion of IL-12p70, IL-6, and TNF-α. These effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2 via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a process that was reversed by the PI3K inhibitor LY294002. Therefore, the regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in the regulation of the statin-mediated antioxidant and anti-inflammatory responses in DCs. Yuanji Ma, Zhaoyang Chen, Yunzeng Zou, and Junbo Ge Copyright © 2014 Yuanji Ma et al. All rights reserved.