Oxidative Medicine and Cellular Longevity https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Increased Oxidative Damage of RNA in Early-Stage Nephropathy in db/db Mice Thu, 19 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/2353729/ To evaluate RNA oxidation in the early stage of diabetic nephropathy, we applied an accurate method based on isotope dilution high-performance liquid chromatography-triple quadruple mass spectrometry to analyze the oxidatively generated guanine nucleosides in renal tissue and urine from db/db mice of different ages. We further investigated the relationship between these oxidative stress markers, microalbumin excretion, and histological changes. We found that the levels of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) were increased in the urine and renal tissue of db/db mice and db/db mice with early symptoms of diabetic nephropathy suffered from more extensive oxidative damage than lean littermate control db/m mice. Importantly, in contrast to the findings in db/m mice, the 8-oxoGuo levels in the urine and renal tissue of db/db mice were higher than those of 8-oxodGuo at four weeks. These results indicate that RNA oxidation is more apparent than DNA oxidation in the early stage of diabetic nephropathy. RNA oxidation may provide new insight into the pathogenesis of diabetic nephropathy, and urinary 8-oxoGuo may represent a novel, noninvasive, and easily detected biomarker of diabetic kidney diseases if further study could clarify its source and confirm these results in a large population study. Wan-Xia Wang, Shun-Bin Luo, Ping Jiang, Meng-Ming Xia, Ai-lian Hei, Yong-Hui Mao, Chuan-Bao Li, Guo-Xin Hu, and Jian-Ping Cai Copyright © 2017 Wan-Xia Wang et al. All rights reserved. Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer’s Disease Thu, 19 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9302761/ Sporadic Alzheimer’s disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer’s pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer’s patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer’s disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients’ fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer’s fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. Patricia Martín-Maestro, Ricardo Gargini, Esther García, George Perry, Jesús Avila, and Vega García-Escudero Copyright © 2017 Patricia Martín-Maestro et al. All rights reserved. Acute Strenuous Exercise Induces an Imbalance on Histone H4 Acetylation/Histone Deacetylase 2 and Increases the Proinflammatory Profile of PBMC of Obese Individuals Thu, 19 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/1530230/ This study evaluated the response of global histone H4 acetylation (H4ac), histone deacetylase 2 (HDAC2) activity, as well as the production of proinflammatory cytokines and monocyte phenotypes of lean and obese males after exercise. Ten lean and ten obese sedentary men were submitted to one session of strenuous exercise, and peripheral blood mononuclear cells (PBMC) were stimulated in vitro with lipopolysaccharide (LPS). Global H4ac levels, HDAC2 activity in PBMC, and IL-6, IL-8, and TNF-α production were analyzed. Monocyte phenotype was determined in accordance with the expression of CD14 and CD16. At rest, obese individuals presented higher frequency of proinflammatory CD14+CD16+ monocytes. LPS induced a significant augment in global H4ac and in the production of IL-6, IL-8, and TNF-α mainly in obese individuals. After exercise, the increased production of IL-8 and TNF-α and peripheral frequency of CD14+CD16+ were observed in both groups. In addition, exercise also induced a significant hyperacetylation of histone H4 and decreased HDAC2 activity in both nonstimulated and LPS-stimulated PBMC of obese individuals. Our data indicate that the obesity impacts on H4ac levels and that strenuous exercise leads to an enhanced chronic low-grade inflammation profile in obesity via an imbalance on H4ac/HDAC2. Gilson P. Dorneles, Maria Carolina R. Boeira, Lucas L. Schipper, Ivy R. V. Silva, Viviane R. Elsner, Pedro Dal Lago, Alessandra Peres, and Pedro R. T. Romão Copyright © 2017 Gilson P. Dorneles et al. All rights reserved. Proinflammatory Cytokines Are Soluble Mediators Linked with Ventricular Arrhythmias and Contractile Dysfunction in a Rat Model of Metabolic Syndrome Thu, 19 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/7682569/ Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25–27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1β (7-fold), TNF-α (84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased gene expression in heart tissue (35-fold). Heart function ex vivo in MS group showed a decreased mechanical performance response to isoproterenol challenge (ISO). Importantly, MS hearts under ISO showed nearly twofold the incidence of ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum displayed impaired contractile function and Ca2+ handling during ISO treatment, showing slightly decreased cell shortening and Ca2+ transient amplitude (23%), slower cytosolic calcium removal (17%), and more frequent spontaneous Ca2+ release events (7.5-fold). As spontaneous Ca2+ releases provide a substrate for ventricular arrhythmias, our study highlights the possible role of serum proinflammatory mediators in the development of arrhythmic events during MS. Evaristo Fernández-Sada, Alejandro Torres-Quintanilla, Christian Silva-Platas, Noemí García, B. Cicero Willis, César Rodríguez-Rodríguez, Erasmo De la Peña, Judith Bernal-Ramírez, Niria Treviño-Saldaña, Yuriana Oropeza-Almazán, Elena C. Castillo, Leticia Elizondo-Montemayor, Karla Carvajal, and Gerardo García-Rivas Copyright © 2017 Evaristo Fernández-Sada et al. All rights reserved. Rhinacanthin C Alleviates Amyloid-β Fibrils’ Toxicity on Neurons and Attenuates Neuroinflammation Triggered by LPS, Amyloid-β, and Interferon-γ in Glial Cells Wed, 18 Oct 2017 05:46:48 +0000 http://www.hindawi.com/journals/omcl/2017/5414297/ Neuroinflammation plays a central role in the pathophysiology of Alzheimer’s disease (AD). Compounds that suppress neuroinflammation have been identified as potential therapeutic targets for AD. Rhinacanthin C (RC), a naphthoquinone ester found in Rhinacanthus nasutus Kurz (Acanthaceae), is currently proposed as an effective molecule against inflammation. However, the exact role of RC on neuroinflammation remains to be elucidated. In the present study, we investigated RC effect on modulating lipopolysaccharides (LPS), amyloid-β peptide (Aβ), or interferon-γ- (IFN-γ-) evoked pathological events in neurons and glia. Our findings demonstrated that RC prevented Aβ-induced toxicity in rat hippocampal neurons and attenuated LPS-activated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and NF-κB signaling in rat glia. Likewise, RC suppressed LPS-induced neuroinflammation by reducing NO production and iNOS, IL-1β, CCL-2, and CCL-5 mRNA levels in rat microglia. Further studies using BV-2 microglia revealed that RC inhibited LPS-, Aβ-, and IFN-γ-stimulated IL-6 and TNF-α secretion. Of note, NF-κB and ERK activation was abrogated by RC in BV-2 cell response to Aβ or IFN-γ. Moreover, RC protected neurons from Aβ-stimulated microglial conditioned media-dependent toxicity. Collectively, these data highlight the beneficial effects of RC on neuroprotection and support the therapeutic implications of RC to neuroinflammation-mediated conditions. Kai-An Chuang, Ming-Han Li, Ni-Hsuan Lin, Chih-Hsuan Chang, I-Huang Lu, I-Hong Pan, Tomoya Takahashi, Ming-Der Perng, and Shu-Fang Wen Copyright © 2017 Kai-An Chuang et al. All rights reserved. Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3 Wed, 18 Oct 2017 04:27:07 +0000 http://www.hindawi.com/journals/omcl/2017/6572714/ Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (), lymphocytes (), and neutrophils () in BAL, as well as BAL levels of IL-1β (), CXCL1 (), IL-17 (), and TNF-α (), while increased the levels of IL-10 (). AE also inhibited smoke-induced increases in total leukocytes (), neutrophils (), lymphocytes (), and monocytes () in blood, as well as serum levels of IL-1β (), CXCL1 (), IL-17 (), and TNF-α (), while increased the levels of IL-10 (). AE reduced smoke-induced emphysema () and collagen fiber accumulation in the airways (). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (), peribronchial leukocytes (), and parenchymal leukocytes (). Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3. Maysa Alves Rodrigues Brandao-Rangel, Andre Luis Lacerda Bachi, Manoel Carneiro Oliveira-Junior, Asghar Abbasi, Adriano Silva-Renno, Auriléia Aparecida de Brito, Ana Paula Ligeiro de Oliveira, Alessandra Choqueta Toledo-Arruda, Maria Gabriela Belvisi, and Rodolfo Paula Vieira Copyright © 2017 Maysa Alves Rodrigues Brandao-Rangel et al. All rights reserved. Oxidative Stress and Cellular Response to Doxorubicin: A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity Wed, 18 Oct 2017 03:31:12 +0000 http://www.hindawi.com/journals/omcl/2017/1521020/ The production of reactive species is a core of the redox cycling profile of anthracyclines. However, these molecular characteristics can be viewed as a double-edged sword acting not only on neoplastic cells but also on multiple cellular targets throughout the body. This phenomenon translates into anthracycline cardiotoxicity that is a serious problem in the growing population of paediatric and adult cancer survivors. Therefore, better understanding of cellular processes that operate within but also go beyond cardiomyocytes is a necessary step to develop more effective tools for the prevention and treatment of progressive and often severe cardiomyopathy experienced by otherwise successfully treated oncologic patients. In this review, we focus on oxidative stress-triggered cellular events such as DNA damage, senescence, and cell death implicated in anthracycline cardiovascular toxicity. The involvement of progenitor cells of cardiac and extracardiac origin as well as different cardiac cell types is discussed, pointing to molecular signals that impact on cell longevity and functional competence. Donato Cappetta, Antonella De Angelis, Luigi Sapio, Lucia Prezioso, Michela Illiano, Federico Quaini, Francesco Rossi, Liberato Berrino, Silvio Naviglio, and Konrad Urbanek Copyright © 2017 Donato Cappetta et al. All rights reserved. Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after Interferon Beta and Melatonin Treatment Wed, 18 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/7905148/ Multiple sclerosis (MS) is a disease involving oxidative stress (OS). This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS), 36 patients with RRMS receiving interferon beta-1b (250 μg every other day), and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily). The levels of N′-formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation products (AGEs), advanced oxidation protein products (AOPP), and malondialdehyde were elevated in nontreated RRSM patients. N′-Formylkynurenine, kynurenine, AGEs, and carbonyl contents were decreased only in the group treated with interferon beta plus melatonin, while dityrosine and AOPP contents were decreased both in the group of patients treated with interferon beta and in the group treated with interferon beta-1b plus melatonin. These results demonstrate that melatonin ameliorates OS in MS patients supporting the view that combined administration of interferon beta-1b and melatonin can be more effective in reducing OS in MS patients than interferon beta-1b alone. Monika Adamczyk-Sowa, Sabina Galiniak, Ewa Żyracka, Michalina Grzesik, Katarzyna Naparło, Paweł Sowa, Grzegorz Bartosz, and Izabela Sadowska-Bartosz Copyright © 2017 Monika Adamczyk-Sowa et al. All rights reserved. Ginger Oleoresin Alleviated γ-Ray Irradiation-Induced Reactive Oxygen Species via the Nrf2 Protective Response in Human Mesenchymal Stem Cells Wed, 18 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/1480294/ Unplanned exposure to radiation can cause side effects on high-risk individuals; meanwhile, radiotherapies can also cause injury on normal cells and tissues surrounding the tumor. Besides the direct radiation damage, most of the ionizing radiation- (IR-) induced injuries were caused by generation of reactive oxygen species (ROS). Human mesenchymal stem cells (hMSCs), which possess self-renew and multilineage differentiation capabilities, are a critical population of cells to participate in the regeneration of IR-damaged tissues. Therefore, it is imperative to search effective radioprotectors for hMSCs. This study was to demonstrate whether natural source ginger oleoresin would mitigate IR-induced injuries in human mesenchymal stem cells (hMSCs). We demonstrated that ginger oleoresin could significantly reduce IR-induced cytotoxicity, ROS generation, and DNA strand breaks. In addition, the ROS-scavenging mechanism of ginger oleoresin was also investigated. The results showed that ginger oleoresin could induce the translocation of Nrf2 to cell nucleus and activate the expression of cytoprotective genes encoding for HO-1 and NQO-1. It suggests that ginger oleoresin has a potential role of being an effective antioxidant and radioprotective agent. Kaihua Ji, Lianying Fang, Hui Zhao, Qing Li, Yang Shi, Chang Xu, Yan Wang, Liqing Du, Jinhan Wang, and Qiang Liu Copyright © 2017 Kaihua Ji et al. All rights reserved. Carlina vulgaris L. as a Source of Phytochemicals with Antioxidant Activity Wed, 18 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/1891849/ The methanol extracts from three populations of Carlina vulgaris L. were examined for the chlorogenic acid content, mineral content, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity. Two populations originated from natural nonmetallicolous habitats (NN (populations from Nasiłów) and NP (populations from Pińczów)), and one metallicolous population (MB) was collected from Bolesław waste heap localized at the place of former open-cast mining of Ag-Pb and Zn-Pb ores dating back to the 13th century and 18th century, respectively. The level of Zn, Pb, Cd, Fe, Ni, and Mn was significantly higher in the root and leaves of MB plants as a result of soil contaminations compared to those of the NN and NP ones. The highest antioxidant potency has been showed by the plants growing in a nonmetallicolous habitat. The flower head extracts obtained from the nonmetallicolous populations also contained the largest amount of chlorogenic acid, whereas the lowest was determined in the roots (ca. 2–3.5 mg/g and 0.2–0.4 mg/g of air-dry weight, resp.). These studies provide important information on the influence of a habitat on the quality of herbal materials and the content of the biologically active primary and secondary metabolites. Maciej Strzemski, Magdalena Wójciak-Kosior, Ireneusz Sowa, Daniel Załuski, Wojciech Szwerc, Jan Sawicki, Ryszard Kocjan, Marcin Feldo, and Sławomir Dresler Copyright © 2017 Maciej Strzemski et al. All rights reserved. Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage Wed, 18 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/4015874/ In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte. Bettina P. Mihalas, Kate A. Redgrove, Eileen A. McLaughlin, and Brett Nixon Copyright © 2017 Bettina P. Mihalas et al. All rights reserved. Protective Effects and Possible Mechanisms of Ergothioneine and Hispidin against Methylglyoxal-Induced Injuries in Rat Pheochromocytoma Cells Tue, 17 Oct 2017 07:38:15 +0000 http://www.hindawi.com/journals/omcl/2017/4824371/ Diabetic encephalopathy (DE) is often a complication in patients with Alzheimer’s disease due to high blood sugar induced by diabetic mellitus. Ergothioneine (EGT) and hispidin (HIP) are antioxidants present in Phellinus linteus. Methylglyoxal (MGO), a toxic precursor of advanced glycated end products (AGEs), is responsible for protein glycation. We investigated whether a combination EGT and HIP (EGT + HIP) protects against MGO-induced neuronal cell damage. Rat pheochromocytoma (PC12) cells were preincubated with EGT (2 μM), HIP (2 μM), or EGT + HIP, then challenged with MGO under high-glucose condition (30 μM MGO + 30 mM glucose; GLU + MGO) for 24–96 h. GLU + MGO markedly increased protein carbonyls and reactive oxygen species in PC12 cells; both of these levels were strongly reduced by EGT or HIP with effects comparable to those of 100 nM aminoguanidine (an AGE inhibitor) but stronger than those of 10 μM epalrestat (an aldose reductase inhibitor). GLU + MGO significantly increased the levels of AGE and AGE receptor (RAGE) protein expression of nuclear factor kappa-B (NF-κB) in the cytosol, but treatment with EGT, HIP, or EGT + HIP significantly attenuated these levels. These results suggest that EGT and HIP protect against hyperglycemic damage in PC12 cells by inhibiting the NF-κB transcription pathway through antioxidant activities. Tuzz-Ying Song, Nae-Cherng Yang, Chien-Lin Chen, and Thuy Lan Vo Thi Copyright © 2017 Tuzz-Ying Song et al. All rights reserved. The Roles of ROS in Cancer Heterogeneity and Therapy Mon, 16 Oct 2017 09:15:25 +0000 http://www.hindawi.com/journals/omcl/2017/2467940/ Cancer comprises a group of heterogeneous diseases encompassing high rates of morbidity and mortality. Heterogeneity, which is a hallmark of cancer, is one of the main factors related to resistance to chemotherapeutic agents leading to poor prognosis. Heterogeneity is profoundly affected by increasing levels of ROS. Under low concentrations, ROS may function as signaling molecules favoring tumorigenesis and heterogeneity, while under high ROS concentrations, these species may work as cancer modulators due to their deleterious, genotoxic or even proapoptotic effect on cancer cells. This double-edged sword effect represented by ROS relies on their ability to cause genetic and epigenetic modifications in DNA structure. Antitumor therapeutic approaches may use molecules that prevent the ROS formation precluding carcinogenesis or use chemical agents that promote a sudden increase of ROS causing considerable oxidative stress inside tumor mass. Therefore, herein, we review what ROS are and how they are produced in normal and in cancer cells while providing an argumentative discussion about their role in cancer pathophysiology. We also describe the various sources of ROS in cancer and their role in tumor heterogeneity. Further, we also discuss some therapeutic strategies from the current landscape of cancer heterogeneity, ROS modulation, or ROS production. Paulo Luiz de Sá Junior, Diana Aparecida Dias Câmara, Allan Saj Porcacchia, Pâmela Maria Moreira Fonseca, Salomão Doria Jorge, Rodrigo Pinheiro Araldi, and Adilson Kleber Ferreira Copyright © 2017 Paulo Luiz de Sá Junior et al. All rights reserved. Corrigendum to “Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury” Mon, 16 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9230134/ Sashko Georgiev Spassov, Rosa Donus, Paul Mikael Ihle, Helen Engelstaedter, Alexander Hoetzel, and Simone Faller Copyright © 2017 Sashko Georgiev Spassov et al. All rights reserved. Uncoupling Protein 2: A Key Player and a Potential Therapeutic Target in Vascular Diseases Sun, 15 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/7348372/ Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension. The deletion of the UCP2 gene contributes to atherosclerosis lesion development in the knockout mice, also showing significantly shorter lifespan. The UCP2 gene downregulation is a key determinant of higher predisposition to renal and cerebrovascular damage in an animal model of spontaneous hypertension and stroke. In contrast, UCP2 overexpression improves both hyperglycemia- and high-salt diet-induced endothelial dysfunction and ameliorates hypertensive target organ damage in SHRSP. Moreover, drugs (fenofibrate and sitagliptin) and several vegetable compounds (extracts from Brassicaceae, berberine, curcumin, and capsaicin) are able to induce UCP2 expression level and to exert beneficial effects on the occurrence of vascular damage. As a consequence, UCP2 becomes an interesting therapeutic target for the treatment of common human vascular diseases. Giorgia Pierelli, Rosita Stanzione, Maurizio Forte, Serena Migliarino, Marika Perelli, Massimo Volpe, and Speranza Rubattu Copyright © 2017 Giorgia Pierelli et al. All rights reserved. Cytoprotective Effects of Citicoline and Homotaurine against Glutamate and High Glucose Neurotoxicity in Primary Cultured Retinal Cells Sun, 15 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/2825703/ Citicoline and homotaurine are renowned compounds that exhibit potent neuroprotective activities through distinct molecular mechanisms. The present study was undertaken to demonstrate whether cotreatment with citicoline and homotaurine affects cell survival in primary retinal cultures under experimental conditions simulating retinal neurodegeneration. Primary cultures were obtained from the retina of fetal rats and exposed to citicoline plus homotaurine (100 μM). Subsequently, neurotoxicity was induced using excitotoxic levels of glutamate and high glucose concentrations. The effects on retinal cultures were assessed by cell viability and immunodetection of apoptotic oligonucleosomes. The results showed that a combination of citicoline and homotaurine synergistically decreases proapoptotic effects associated with glutamate- and high glucose-treated retinal cultures. This study provides an insight into the potential application of citicoline and homotaurine as a valuable tool to exert neuroprotective effects against retinal damage. Sergio Davinelli, Flavia Chiosi, Roberto Di Marco, Ciro Costagliola, and Giovanni Scapagnini Copyright © 2017 Sergio Davinelli et al. All rights reserved. Effect of Chronic Administration of Resveratrol on Cognitive Performance during Aging Process in Rats Sun, 15 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8510761/ The increase in the elderly population has generated concern to meet health demands. The research efforts to elucidate the mechanisms of damage associated with aging have also been significantly increased, especially in order to avoid the reduction of the cognitive abilities in geriatric patients, resulting from the damage generated mainly at the level of the hippocampus during old age. At present, many studies describe resveratrol as an antiaging component. There are reports that it can activate the Sirt1 gene related to antiaging, emulating the effects obtained by caloric restriction in rodents. The aim of the study was to evaluate the effect of chronic administration of resveratrol (10 mg/kg) on cognitive performance in behavioral tests after 8 months of treatment and on the preservation of cerebral integrity in the cytoarchitecture of regions CA1 and CA2. Results showed that the cytoarchitecture of the CA1 and CA2 regions in the hippocampus retained their integrity over time in rats treated with resveratrol, and the behavioral test performed revealed that chronic resveratrol administration for 8 months showed improvements in cognitive performance. The results indicate that resveratrol may exhibit therapeutic potential for age-related conditions. A. R. Navarro-Cruz, R. Ramírez y Ayala, C. Ochoa-Velasco, E. Brambila, R. Avila-Sosa, S. Pérez-Fernández, J. C. Morales-Medina, and P. Aguilar-Alonso Copyright © 2017 A. R. Navarro-Cruz et al. All rights reserved. Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity Sun, 15 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/6034692/ 2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway. Qun Shan, Juan Zhuang, Guihong Zheng, Zifeng Zhang, Yanqiu Zhang, Jun Lu, and Yuanlin Zheng Copyright © 2017 Qun Shan et al. All rights reserved. Neuroprotective and Cognitive-Enhancing Effects of Microencapsulation of Mulberry Fruit Extract in Animal Model of Menopausal Women with Metabolic Syndrome Thu, 12 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/2962316/ Currently, the neuroprotectant and memory-enhancing agent for menopausal women with metabolic syndrome is required. Based on the advantages of polyphenolics on numerous changes observed in menopause with metabolic syndrome and the encapsulation method, we hypothesized that microencapsulated mulberry fruit extract (MME) could protect brain damage and improve memory impairment in an animal model of menopause with metabolic syndrome. To test this hypothesis, MME at doses of 10, 50, and 250 mg/kg was given to female Wistar rats which were induced experimental menopause with metabolic syndrome by bilateral ovariectomy (OVX) and fed with high-carbohydrate high-fat (HCHF) diet for 8 weeks. Spatial memory together with neuron density, oxidative stress status, acetylcholinesterase, and phosphorylation of Erk in the hippocampus was assessed at the end of the study. It was found that MME decreased memory impairment, oxidative stress status, and AChE activity but increased neuron density and Erk phosphorylation in the hippocampus. Therefore, the neuroprotective and memory-enhancing effects of MME might partly involve the enhanced cholinergic function and Erk phosphorylation but decreased oxidative stress status in hippocampus. Therefore, MME is the potential novel neuroprotectant and memory-enhancing agent for menopause with metabolic syndrome. However, further research especially clinical trial is still necessary. Supannika Kawvised, Jintanaporn Wattanathorn, and Wipawee Thukham-mee Copyright © 2017 Supannika Kawvised et al. All rights reserved. Effects of Novel Nitric Oxide-Releasing Molecules against Oxidative Stress on Retinal Pigmented Epithelial Cells Thu, 12 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/1420892/ Oxidative stress is a hallmark of retinal degenerations such as age-related macular degeneration and diabetic retinopathy. Enhancement of heme oxygenase-1 (HO-1) activity in the retina would exert beneficial effects by protecting cells from oxidative stress, therefore promoting cell survival. Because a crosstalk exists between nitric oxide (NO) and HO-1 in promotion of cell survival under oxidative stress, we designed novel NO-releasing molecules also capable to induce HO-1. Starting from curcumin and caffeic acid phenethyl ester (CAPE), two known HO-1 inducers, the molecules were chemically modified by acylation with 4-bromo-butanoyl chloride and 2-chloro-propanoyl chloride, respectively, and then treated in the dark with AgNO3 to obtain the nitrate derivatives VP10/12 and VP10/39. Human retinal pigment epithelial cells (ARPE-19) subjected to H2O2-mediated oxidative stress were treated with the described NO-releasing compounds. VP10/39 showed significant () antioxidant and protecting activity against oxidative damage, in comparison to VP10/12, which in turn showed at 100 μM concentration a slight but significant cell toxicity. Only VP10/39 significantly () induced HO-1 in ARPE-19, most likely through covalent bond formation at Cys151 of the Keap1-BTB domain, as revealed from molecular docking analysis. In conclusion, the present data indicate VP10/39 as a promising candidate to protect ARPE-19 cells against oxidative stress. Valeria Pittalà, Annamaria Fidilio, Francesca Lazzara, Chiara Bianca Maria Platania, Loredana Salerno, Roberta Foresti, Filippo Drago, and Claudio Bucolo Copyright © 2017 Valeria Pittalà et al. All rights reserved. Contribution and Interactions of Hydroxycinnamic Acids Found in Bran and Wholegrain Sorghum (Sorghum bicolor L. Moench): Effects on the Antioxidant Capacity and Inhibition of Human Erythrocyte Hemolysis Thu, 12 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8219023/ An imbalance between free radicals and antioxidants is known as oxidative stress, and it promotes cellular aging and the development of chronic noncommunicable diseases. The bioactive compounds present in food play an important role in preventing oxidative stress. The aim of this study was to determine the contributions and interactions of the hydroxycinnamic acids found in the bran and whole grain of sorghum and to evaluate their effects on the antioxidant capacity and inhibition of the hemolysis of human erythrocytes. Results showed that the caffeic acid, p-coumaric acid, and ferulic acid found in sorghum contributed to the scavenging of DPPH and ABTS radicals in various proportions. Ferulic acid, which was present in bound form in the bran and wholegrain sorghum, significantly inhibited the AAPH radical-induced oxidation of the erythrocyte membranes by 78.0 and 4.3%, respectively. Combinations of two, three, or four hydroxycinnamic acids may interact in an antagonistic or synergistic manner, thereby altering each other’s bioactivities. The various interactions between the different sorghum bioactives can have a significant impact on their potential bioactivities. These results can be useful in the design of functional foods that aim to deliver bioactives to mitigate cellular aging or noncommunicable diseases. Norma Julieta Salazar-López, Gustavo A. González-Aguilar, Guadalupe Loarca-Piña, Francisco J. Cinco-Moroyoqui, Ofelia Rouzaud-Sández, J. Abraham Domínguez-Avila, and Maribel Robles-Sánchez Copyright © 2017 Norma Julieta Salazar-López et al. All rights reserved. Mitochondria-Targeted Antioxidant SkQ1 Prevents Anesthesia-Induced Dry Eye Syndrome Thu, 12 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9281519/ Dry eye syndrome (DES) is an age-related condition increasingly detected in younger people of risk groups, including patients who underwent ocular surgery or long-term general anesthesia. Being a multifactorial disease, it is characterized by oxidative stress in the cornea and commonly complicated by ocular surface inflammation. Polyetiologic DES is responsive to SkQ1, a mitochondria-targeted antioxidant suppressing age-related changes in the ocular tissues. Here, we demonstrate safety and efficacy of topical administration of SkQ1 at a dosage of 7.5 μM for the prevention of general anesthesia-induced DES in rabbits. The protective action of SkQ1 improves clinical state of the ocular surface by inhibiting apoptotic and prenecrotic changes in the corneal epithelium. The underlying mechanism involves the suppression of the oxidative stress supported by the stimulation of intrinsic antioxidant activity and the activity of antioxidant enzymes, foremost glutathione peroxidase and glutathione reductase, in the cornea. Furthermore, SkQ1 increases antioxidant activity and stability of the tear film and produces anti-inflammatory effect exhibited as downregulation of TNF-α and IL-6 and pronounced upregulation of IL-10 in tears. Our data suggest novel features of SkQ1 and point to its feasibility in patients with DES and individuals at risk for the disease including those subjected to general anesthesia. Evgeni Yu. Zernii, Olga S. Gancharova, Viktoriia E. Baksheeva, Marina O. Golovastova, Ekaterina I. Kabanova, Marina S. Savchenko, Veronika V. Tiulina, Larisa F. Sotnikova, Andrey A. Zamyatnin Jr., Pavel P. Philippov, and Ivan I. Senin Copyright © 2017 Evgeni Yu. Zernii et al. All rights reserved. Ghrelin Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Damage Tue, 10 Oct 2017 08:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/1910450/ Oxidative stress has been recognized as an important mediator in the pathogenesis of age-related cataracts; using antioxidant supplements is one plausible strategy to protect the antioxidative defense system against oxidative stress. Ghrelin administration is expected to reduce ROS, preventing the onset of different diseases. The role of ghrelin, if any, in protecting against oxidative stress in HLECs has never been examined. In the present study, we investigated the effects of ghrelin against H2O2-induced oxidative stress and the associated molecular mechanisms in HLECs and rat lenses. The results showed that pretreatment with ghrelin reduced H2O2-induced cellular apoptosis and ROS accumulation, increased the expression levels of SOD and CAT, and decreased the expression level of MDA. The morphological examination showed that the ghrelin-treated lens organ culture maintained transparency. This is the first report to show that ghrelin can protect HLECs from H2O2-induced oxidative stress. Our findings suggest that ghrelin may prevent the progression of cataracts, which has treatment value for ophthalmologists. Jie Bai, Fan Yang, Li Dong, and Yi Zheng Copyright © 2017 Jie Bai et al. All rights reserved. Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin Tue, 10 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/2734976/ The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy. Gabriela Carrasco-Torres, Rafael Baltiérrez-Hoyos, Erik Andrade-Jorge, Saúl Villa-Treviño, José Guadalupe Trujillo-Ferrara, and Verónica Rocío Vásquez-Garzón Copyright © 2017 Gabriela Carrasco-Torres et al. All rights reserved. Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide-Dependent Tolerance Pathway Tue, 10 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/4064628/ Amphotericin B (AmB) induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB’s fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB’s action. Hence, superoxide radicals were important for AmB’s fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections. Kim Vriens, Phalguni Tewari Kumar, Caroline Struyfs, Tanne L. Cools, Pieter Spincemaille, Tadej Kokalj, Belém Sampaio-Marques, Paula Ludovico, Jeroen Lammertyn, Bruno P. A. Cammue, and Karin Thevissen Copyright © 2017 Kim Vriens et al. All rights reserved. Effect of ALDH2 on High Glucose-Induced Cardiac Fibroblast Oxidative Stress, Apoptosis, and Fibrosis Mon, 09 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9257967/ Our study aimed firstly to observe whether ALDH2 was expressed in neonate rat cardiac fibroblasts, then to investigate the effect of activation of ALDH2 on oxidative stress, apoptosis, and fibrosis when cardiac fibroblasts were subjected to high glucose intervention. Cultured cardiac fibroblasts were randomly divided into normal (NG), NG + Alda-1, high glucose (HG), HG + Alda-1, HG + Alda-1 + daidzin, HG + daidzin, and hypertonic groups. Double-label immunofluorescence staining, RT-PCR, and Western blot revealed ALDH2 was expressed in cardiac fibroblasts. Compared with NG, ALDH2 activity and protein expression were reduced, and cardiac fibroblast proliferation, ROS releasing, 4-HNE protein expression, collagen type I and III at mRNA levels, and the apoptosis rate were increased in HG group. While in HG + Alda-1 group, with the increases of ALDH2 activity and protein expression, the cardiac fibroblast proliferation and ROS releasing were decreased, and 4-HNE protein expression, collagen type I and III at mRNA levels, and apoptosis rate were reduced compared with HG group. When treated with daidzin in HG + Alda-1 group, the protective effects were inhibited. Our findings suggested that ALDH2 is expressed in neonate rat cardiac fibroblasts; activation of ALDH2 decreases the HG-induced apoptosis and fibrosis through inhibition of oxidative stress. Xiaoyu Gu, Tingting Fang, Pinfang Kang, Junfeng Hu, Ying Yu, Zhenghong Li, Xiangyang Cheng, and Qin Gao Copyright © 2017 Xiaoyu Gu et al. All rights reserved. New Insights into the Benefits of Physical Activity and Exercise for Aging and Chronic Disease Sun, 08 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/2503767/ James E. Turner, Vitor A. Lira, and Patricia C. Brum Copyright © 2017 James E. Turner et al. All rights reserved. Redox Regulation of Inflammatory Processes Is Enzymatically Controlled Sun, 08 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8459402/ Redox regulation depends on the enzymatically controlled production and decay of redox active molecules. NADPH oxidases, superoxide dismutases, nitric oxide synthases, and others produce the redox active molecules superoxide, hydrogen peroxide, nitric oxide, and hydrogen sulfide. These react with target proteins inducing spatiotemporal modifications of cysteine residues within different signaling cascades. Thioredoxin family proteins are key regulators of the redox state of proteins. They regulate the formation and removal of oxidative modifications by specific thiol reduction and oxidation. All of these redox enzymes affect inflammatory processes and the innate and adaptive immune response. Interestingly, this regulation involves different mechanisms in different biological compartments and specialized cell types. The localization and activity of distinct proteins including, for instance, the transcription factor NFκB and the immune mediator HMGB1 are redox-regulated. The transmembrane protein ADAM17 releases proinflammatory mediators, such as TNFα, and is itself regulated by a thiol switch. Moreover, extracellular redox enzymes were shown to modulate the activity and migration behavior of various types of immune cells by acting as cytokines and/or chemokines. Within this review article, we will address the concept of redox signaling and the functions of both redox enzymes and redox active molecules in innate and adaptive immune responses. Inken Lorenzen, Lisa Mullen, Sander Bekeschus, and Eva-Maria Hanschmann Copyright © 2017 Inken Lorenzen et al. All rights reserved. Magnesium and Other Biometals in Oxidative Medicine and Redox Biology Wed, 04 Oct 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/7428796/ Martin Kolisek, Rhian M. Touyz, Andrea Romani, and Mario Barbagallo Copyright © 2017 Martin Kolisek et al. All rights reserved. Cardioprotective Effect of Resveratrol in a Postinfarction Heart Failure Model Tue, 03 Oct 2017 06:13:42 +0000 http://www.hindawi.com/journals/omcl/2017/6819281/ Despite great advances in therapies observed during the last decades, heart failure (HF) remained a major health problem in western countries. In order to further improve symptoms and survival in patients with heart failure, novel therapeutic strategies are needed. In some animal models of HF resveratrol (RES), it was able to prevent cardiac hypertrophy, contractile dysfunction, and remodeling. Several molecular mechanisms are thought to be involved in its protective effects, such as inhibition of prohypertrophic signaling molecules, improvement of myocardial Ca2+ handling, regulation of autophagy, and the reduction of oxidative stress and inflammation. In our present study, we wished to further examine the effects of RES on prosurvival (Akt-1, GSK-3β) and stress signaling (p38-MAPK, ERK 1/2, and MKP-1) pathways, on oxidative stress (iNOS, COX-2 activity, and ROS formation), and ultimately on left ventricular function, hypertrophy and fibrosis in a murine, and isoproterenol- (ISO-) induced postinfarction heart failure model. RES treatment improved left ventricle function, decreased interstitial fibrosis, cardiac hypertrophy, and the level of plasma BNP induced by ISO treatment. ISO also increased the activation of P38-MAPK, ERK1/2Thr183-Tyr185, COX-2, iNOS, and ROS formation and decreased the phosphorylation of Akt-1, GSK-3β, and MKP-1, which were favorably influenced by RES. According to our results, regulation of these pathways may also contribute to the beneficial effects of RES in HF. Adam Riba, Laszlo Deres, Balazs Sumegi, Kalman Toth, Eszter Szabados, and Robert Halmosi Copyright © 2017 Adam Riba et al. All rights reserved.