Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Oxidative Stress as Estimated by Gamma-Glutamyl Transferase Levels Amplifies the Alkaline Phosphatase-Dependent Risk for Mortality in ESKD Patients on Dialysis Mon, 25 Jul 2016 08:51:58 +0000 http://www.hindawi.com/journals/omcl/2016/8490643/ Alkaline phosphatase (Alk-Phos) is a powerful predictor of death in patients with end-stage kidney disease (ESKD) and oxidative stress is a strong inducer of Alk-Phos in various tissues. We tested the hypothesis that oxidative stress, as estimated by a robust marker of systemic oxidative stress like γ-Glutamyl-Transpeptidase (GGT) levels, may interact with Alk-Phos in the high risk of death in a cohort of 993 ESKD patients maintained on chronic dialysis. In fully adjusted analyses the HR for mortality associated with Alk-Phos (50 IU/L increase) was progressively higher across GGT quintiles, being minimal in patients in the first quintile (HR: 0.89, 95% CI: 0.77–1.03) and highest in the GGT fifth quintile (HR: 1.13, 95% CI: 1.03–1.2) ( for the effect modification = 0.02). These findings were fully confirmed in sensitivity analyses excluding patients with preexisting liver disease, excessive alcohol intake, or altered liver disease biomarkers. GGT amplifies the risk of death associated with high Alk-Phos levels in ESKD patients. This observation is compatible with the hypothesis that oxidative stress is a strong modifier of the adverse biological effects of high Alk-Phos in this population. Claudia Torino, Francesco Mattace-Raso, Jan L. C. M. van Saase, Maurizio Postorino, Giovanni Luigi Tripepi, Francesca Mallamaci, Carmine Zoccali, and PROGREDIRE Study Group Copyright © 2016 Claudia Torino et al. All rights reserved. Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress-Induced Oxidative Stress in Hippocampus by Upregulation of BDNF-TrkB Pathway Mon, 25 Jul 2016 08:33:53 +0000 http://www.hindawi.com/journals/omcl/2016/2153745/ Chronic unpredictable mild stress (CUMS) induces hippocampal oxidative stress. H2S functions as a neuroprotectant against oxidative stress in brain. We have previously shown the upregulatory effect of H2S on BDNF protein expression in the hippocampus of rats. Therefore, we hypothesized that H2S prevents CUMS-generated oxidative stress by upregulation of BDNF-TrkB pathway. We showed that NaHS (0.03 or 0.1 mmol/kg/day) ameliorates the level of hippocampal oxidative stress, including reduced levels of malondialdehyde (MDA) and 4-hydroxy-2-trans-nonenal (4-HNE), as well as increased level of glutathione (GSH) and activity of superoxide dismutase (SOD) in the hippocampus of CUMS-treated rats. We also found that H2S upregulated the level of BDNF and p-TrkB protein in the hippocampus of CUMS rats. Furthermore, inhibition of BDNF signaling by K252a, an inhibitor of the BDNF receptor TrkB, blocked the antioxidant effects of H2S on CUMS-induced hippocampal oxidative stress. These results reveal the inhibitory role of H2S in CUMS-induced hippocampal oxidative stress, which is through upregulation of BDNF/TrkB pathway. Min Hu, Wei Zou, Chun-Yan Wang, Xi Chen, Hui-Ying Tan, Hai-Ying Zeng, Ping Zhang, Hong-Feng Gu, and Xiao-Qing Tang Copyright © 2016 Min Hu et al. All rights reserved. Low-Dose Methylmercury-Induced Apoptosis and Mitochondrial DNA Mutation in Human Embryonic Neural Progenitor Cells Thu, 21 Jul 2016 13:18:59 +0000 http://www.hindawi.com/journals/omcl/2016/5137042/ Methylmercury (MeHg) is a long-lasting organic pollutant primarily found in the aquatic environment. The developing brain is particularly sensitive to MeHg due to reduced proliferation of neural stem cell. Although several mechanisms of MeHg-induced apoptosis have been defined in culture models, it remains unclear whether mitochondrial DNA (mtDNA) mutation is involved in the toxic effect of MeHg, especially in the neural progenitor cells. In the present study, the ReNcell CX cell, a human neural progenitor cells (hNPCs) line, was exposed to nanomolar concentrations of MeHg (≤50 nM). We found that MeHg altered mitochondrial metabolic function and induced apoptosis. In addition, we observed that MeHg induced ROS production in a dose-dependent manner in hNPCs cells, which was associated with significantly increased expressions of ND1, Cytb, and ATP6. To elucidate the mechanism underlying MeHg toxicity on mitochondrial function, we examined the ATP content and mitochondrial membrane potential in MeHg-treated hNPCs. Our study showed that MeHg exposure led to decreased ATP content and reduced mitochondrial membrane potential, which failed to match the expansion in mtDNA copy number, suggesting impaired mtDNA. Collectively, these results demonstrated that MeHg induced toxicity in hNPCs through altering mitochondrial function and inducing oxidative damage to mtDNA. Xinjin Wang, Mengling Yan, Lina Zhao, Qing Wu, Chunhua Wu, Xiuli Chang, and Zhijun Zhou Copyright © 2016 Xinjin Wang et al. All rights reserved. Cord Blood Adiponectin and Visfatin Concentrations in relation to Oxidative Stress Markers in Neonates Exposed and Nonexposed In Utero to Tobacco Smoke Wed, 20 Jul 2016 09:33:34 +0000 http://www.hindawi.com/journals/omcl/2016/4569108/ Aims. Maternal smoking is considered as a source of oxidative stress, which has been implicated to disrupted adipokines expression in adipose tissue. We examined the relationship between selected adipokines and markers of oxidative stress/antioxidant defence in the umbilical cord of neonates exposed and nonexposed in utero to tobacco smoke. Methods. Subjects including 85 healthy neonates (born to 41 smokers and 44 nonsmokers) were tested for adiponectin, visfatin, oxidized low density lipoprotein (ox-LDL), total oxidant capacity (TOC), and total antioxidant capacity (TAC). Results. Cord serum visfatin, ox-LDL, and TOC were significantly higher () but adiponectin and TAC were lower ( and , resp.) in smoking group than in tobacco abstinents. In whole group of children (adjusted for smoking status, gender, and birth weight) adiponectin showed negative and visfatin positive correlations with ox-LDL. In the model estimated separately for smokers ox-LDL explained 36% of adiponectin and 35.5% of visfatin variance, while in the model of nonsmokers it explained 36.8% and 69.4%, respectively. Conclusion. Maternal smoking enhances oxidative status and depletes antioxidant potential in newborns. Lower level of adiponectin and higher visfatin concentration seem to be related with a less beneficial oxidative stress profile and higher level of lipid peroxidation in neonates exposed and nonexposed in utero to tobacco smoke. Magdalena Chełchowska, Jadwiga Ambroszkiewicz, Joanna Gajewska, Grażyna Rowicka, Tomasz M. Maciejewski, and Joanna Mazur Copyright © 2016 Magdalena Chełchowska et al. All rights reserved. Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages Tue, 19 Jul 2016 14:06:01 +0000 http://www.hindawi.com/journals/omcl/2016/7124251/ High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels. Dana Atrahimovich, Soliman Khatib, Shifra Sela, Jacob Vaya, and Abraham O. Samson Copyright © 2016 Dana Atrahimovich et al. All rights reserved. Redox Imbalance and Stroke Tue, 19 Jul 2016 07:22:55 +0000 http://www.hindawi.com/journals/omcl/2016/3065263/ Ruidong Ye, Ming Shi, Qian Liu, and Jieli Chen Copyright © 2016 Ruidong Ye et al. All rights reserved. Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B Mon, 18 Jul 2016 17:26:37 +0000 http://www.hindawi.com/journals/omcl/2016/8696587/ The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals. Yuhan Tang, Juan Li, Chao Gao, Yanyan Xu, Yanyan Li, Xiao Yu, Jing Wang, Liegang Liu, and Ping Yao Copyright © 2016 Yuhan Tang et al. All rights reserved. Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox Status and ROS Production according to Duration of a Competitive Race Mon, 18 Jul 2016 13:48:36 +0000 http://www.hindawi.com/journals/omcl/2016/6439037/ Purpose. Response to an ultraendurance competitive race on thiols redox status, reactive oxygen species (ROS) production, and oxidative stress (OxS) was investigated according to duration. Methods. Twenty-four elite runners were examined: six completed 50 km and eighteen 100 km. Blood and urine samples were collected before and immediately after the race. Erythrocytes and plasma aminothiols by high-performance liquid chromatography, total antioxidant capacity (TAC), and OxS biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS), 8-isoprostane (8-iso-PGF2α), and 8-OH-2-deoxyguanosine (8-OH-dG)) by immunoenzymatic assays and ROS production by Electron Paramagnetic Resonance were assessed. Results. Significant increases ( between <0.05 and <0.0001) were recorded in plasma total and oxidized aminothiols concentration and TAC () only after 100 km: plasmatic (ROS production (+12 versus +29%), PC (+54 versus +115%), and TBARS (+28 versus +55%)) and urinary (8-OH-dG.creatinine−1 (+71 versus +158%) and 8-iso-PGF2α.creatinine−1 (+43 versus +135%)) concentrations for 50 and 100 km (duration 4 h 3′ versus 8 h 42′), respectively. Conclusion. Very prolonged ultraendurance exercise causes an increase in ROS production and OxS depending on specific biomarker examined but always linearly and directly related to exercise duration. Redox status of erythrocytes was preserved. A relationship between running performance and both prerace ROS production and antioxidant-redox status was found in 100 km race. Alessandra Vezzoli, Cinzia Dellanoce, Simona Mrakic-Sposta, Michela Montorsi, Sarah Moretti, Annamaria Tonini, Lorenza Pratali, and Roberto Accinni Copyright © 2016 Alessandra Vezzoli et al. All rights reserved. “Cumulative Stress”: The Effects of Maternal and Neonatal Oxidative Stress and Oxidative Stress-Inducible Genes on Programming of Atopy Mon, 18 Jul 2016 08:20:10 +0000 http://www.hindawi.com/journals/omcl/2016/8651820/ Although extensive epidemiological and laboratory studies have been performed to identify the environmental and immunological causes of atopy, genetic predisposition seems to be the biggest risk factor for allergic diseases. The onset of atopic diseases may be the result of heritable changes of gene expression, without any alteration in DNA sequences occurring in response to early environmental stimuli. Findings suggest that the establishment of a peculiar epigenetic pattern may also be generated by oxidative stress (OS) and perpetuated by the activation of OS-related genes. Analyzing the role of maternal and neonatal oxidative stress and oxidative stress-inducible genes, the purpose of this review was to summarize what is known about the relationship between maternal and neonatal OS-related genes and the development of atopic diseases. Sara Manti, Lucia Marseglia, Gabriella D’Angelo, Caterina Cuppari, Erika Cusumano, Teresa Arrigo, Eloisa Gitto, and Carmelo Salpietro Copyright © 2016 Sara Manti et al. All rights reserved. Comment on “Use of Carnosine for Oxidative Stress Reduction in Different Pathologies” Sun, 17 Jul 2016 12:24:07 +0000 http://www.hindawi.com/journals/omcl/2016/5250386/ S. V. Jargin Copyright © 2016 S. V. Jargin. All rights reserved. Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells Sun, 17 Jul 2016 06:32:38 +0000 http://www.hindawi.com/journals/omcl/2016/2594703/ 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER) stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308), and p-mTOR (Ser2481) were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin. Han Sung Kim, Tae-Young Han, and Yeong-Min Yoo Copyright © 2016 Han Sung Kim et al. All rights reserved. Antioxidant and Antihyperlipidemic Effects of Campomanesia adamantium O. Berg Root Thu, 14 Jul 2016 11:18:31 +0000 http://www.hindawi.com/journals/omcl/2016/7910340/ Campomanesia adamantium O. Berg, popularly known as guavira, has been used in Brazilian traditional medicine for reduction of serum lipid. The present study was carried out to investigate the antioxidant and antihyperlipidemic effects of Campomanesia adamantium root aqueous extract (ExCA). Phenolic compounds were quantified in the ExCA and gallic and ellagic acids were identified by HPLC. ExCA showed efficiency in 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, with IC50 similar to butylhydroxytoluene control, and protected the erythrocytes against lipid peroxidation induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride, reducing generated malondialdehyde. Hyperlipidemic Wistar rats treated daily by gavage during eight weeks with ExCA (200 mg/kg of body weight) showed reduced serum level of total cholesterol and triglycerides, similar to normolipidemic rats and hyperlipidemic rats treated with simvastatin (30 mg/kg of body weight) and ciprofibrate (2 mg/kg of body weight). Moreover, the treatment with ExCA also decreased malondialdehyde serum level in the hyperlipidemic rats. The body weight and organ mass were unmodified by ExCA in hyperlipidemic rats, except an increase of liver mass; however, the hepatic enzymes, alanine aminotransferase and aspartate aminotransferase, were unchanged. Together, these results confirm the potential value of Campomanesia adamantium root for lowering lipid peroxidation and lipid serum level, improving risk factors for cardiometabolic diseases development. Priscilla Pereira de Toledo Espindola, Paola dos Santos da Rocha, Carlos Alexandre Carollo, Wanderlei Onofre Schmitz, Zefa Valdivina Pereira, Maria do Carmo Vieira, Edson Lucas dos Santos, and Kely de Picoli Souza Copyright © 2016 Priscilla Pereira de Toledo Espindola et al. All rights reserved. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury Thu, 14 Jul 2016 06:04:27 +0000 http://www.hindawi.com/journals/omcl/2016/9247493/ Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity. Daniela Hoeber, Marco Sifringer, Yohan van de Looij, Josephine Herz, Stéphane V. Sizonenko, Karina Kempe, Meray Serdar, Joanna Palasz, Martin Hadamitzky, Stefanie Endesfelder, Joachim Fandrey, Ursula Felderhoff-Müser, and Ivo Bendix Copyright © 2016 Daniela Hoeber et al. All rights reserved. Mitochondrial Health in Aging and Age-Related Metabolic Disease Wed, 13 Jul 2016 11:55:35 +0000 http://www.hindawi.com/journals/omcl/2016/5831538/ David Sebastián, Rebeca Acín-Pérez, and Katsutaro Morino Copyright © 2016 David Sebastián et al. All rights reserved. Role of ROS and RNS Sources in Physiological and Pathological Conditions Tue, 12 Jul 2016 14:32:05 +0000 http://www.hindawi.com/journals/omcl/2016/1245049/ There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis. Sergio Di Meo, Tanea T. Reed, Paola Venditti, and Victor Manuel Victor Copyright © 2016 Sergio Di Meo et al. All rights reserved. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin Tue, 12 Jul 2016 09:52:35 +0000 http://www.hindawi.com/journals/omcl/2016/5846865/ Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm2) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage. Bing-rong Zhou, Li-wen Ma, Juan Liu, Jia-an Zhang, Yang Xu, Di Wu, Felicia Permatasari, and Dan Luo Copyright © 2016 Bing-rong Zhou et al. All rights reserved. Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones Mon, 11 Jul 2016 08:54:06 +0000 http://www.hindawi.com/journals/omcl/2016/3285074/ Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H2S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H2S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H2S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H2S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H2S in hepatic glucose output and adipose glucose uptake. The mechanism of H2S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H2S in other metabolic and glucoregulatory hormone secreting tissues are proposed. Jennifer Pichette and Jeffrey Gagnon Copyright © 2016 Jennifer Pichette and Jeffrey Gagnon. All rights reserved. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls Sun, 10 Jul 2016 09:22:22 +0000 http://www.hindawi.com/journals/omcl/2016/9346470/ Inflammatory bowel diseases (IBDs) are characterized by autoimmune and inflammation-related complications of the large intestine (ulcerative colitis) and additional parts of the digestive tract (Crohn’s disease). Complications include pain, diarrhoea, chronic inflammation, and cancer. IBD prevalence has increased during the past decades, especially in Westernized countries, being as high as 1%. As prognosis is poor and medication often ineffective or causing side effects, additional preventive/adjuvant strategies are sought. A possible approach is via diets rich in protective constituents. Polyphenols, the most abundant phytochemicals, have been associated with anti-inflammatory, antioxidant, immunomodulatory, and apoptotic properties. Locally reducing oxidative stress, they can further act on cellular targets, altering gene expression related to inflammation, including NF-κB, Nrf-2, Jak/STAT, and MAPKs, suppressing downstream cytokine formation (e.g., IL-8, IL-1β, and TNF-α), and boosting the bodies’ own antioxidant status (HO-1, SOD, and GPx). Moreover, they may promote, as prebiotics, healthy microbiota (e.g., Bifidobacteria, Akkermansia), short-chain fatty acid formation, and reduced gut permeability/improved tight junction stability. However, potential adverse effects such as acting as prooxidants, or perturbations of efflux transporters and phase I/II metabolizing enzymes, with increased uptake of undesired xenobiotics, should also be considered. In this review, we summarize current knowledge around preventive and arbitrary actions of polyphenols targeting IBD. Anouk Kaulmann and Torsten Bohn Copyright © 2016 Anouk Kaulmann and Torsten Bohn. All rights reserved. Redox Signaling and Myocardial Cell Death: Molecular Mechanisms and Drug Targets Sun, 03 Jul 2016 07:31:52 +0000 http://www.hindawi.com/journals/omcl/2016/3190753/ Mohanraj Rajesh, Lu Cai, Partha Mukhopadhyay, and Srinivasan Vedantham Copyright © 2016 Mohanraj Rajesh et al. All rights reserved. Glutathione as a Biomarker in Parkinson’s Disease: Associations with Aging and Disease Severity Thu, 30 Jun 2016 13:30:03 +0000 http://www.hindawi.com/journals/omcl/2016/9409363/ Objectives. Oxidative stress contributes to Parkinson’s disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity. Methods. 58 otherwise healthy individuals with PD were examined during a single study visit. Descriptive statistics and scatterplots were used to evaluate normality and distribution of this cross-sectional sample. Blood tests and magnetic resonance spectroscopy (MRS) were used to collect biologic data. Spearman’s rank-order correlation coefficients were used to evaluate the strength and direction of the association. The Unified PD Rating Scale (UPDRS) and the Patient-Reported Outcomes in PD (PRO-PD) were used to rate disease severity using regression analysis. Results. Blood measures of Glu decreased with age, although there was no age-related decline in MRS Glu. The lower the blood Glu concentration, the more severe the UPDRS (, 95% CI: −13.96, −1.14) and the PRO-PD (, 95% CI: −0.83, −0.11) scores. Discussion. These data suggest whole blood Glu may have utility as a biomarker in PD. Future studies should evaluate whether it is a modifiable risk factor for PD progression and whether Glu fortification improves PD outcomes. Laurie K. Mischley, Leanna J. Standish, Noel S. Weiss, Jeannie M. Padowski, Terrance J. Kavanagh, Collin C. White, and Michael E. Rosenfeld Copyright © 2016 Laurie K. Mischley et al. All rights reserved. Tissue Kallikrein Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the B2R-ERK1/2-CREB-Bcl-2 Signaling Pathway in Diabetic Rats Thu, 30 Jun 2016 13:25:23 +0000 http://www.hindawi.com/journals/omcl/2016/1843201/ Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin-induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response element-binding (CREB), and Bcl-2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin-induced diabetic rats mainly involves the enhancement of B2R and ERK1/2-CREB-Bcl-2 signaling pathway activity. Ruifeng Shi, Kunxiong Yuan, Bin Hu, Hongfei Sang, Lizhi Zhou, Yi Xie, Lili Xu, Qinqin Cao, Xin Chen, Lingling Zhao, Yunyun Xiong, Gelin Xu, Xinfeng Liu, Ling Liu, and Renliang Zhang Copyright © 2016 Ruifeng Shi et al. All rights reserved. Neoatherosclerosis after Drug-Eluting Stent Implantation: Roles and Mechanisms Thu, 30 Jun 2016 09:36:30 +0000 http://www.hindawi.com/journals/omcl/2016/5924234/ In-stent neoatherosclerosis (NA), characterized by a relatively thin fibrous cap and large volume of yellow-lipid accumulation after drug-eluting stents (DES) implantation, has attracted much attention owing to its close relationship with late complications, such as revascularization and late stent thrombosis (ST). Accumulating evidence has demonstrated that more than one-third of patients with first-generation DES present with NA. Even in the advent of second-generation DES, NA still occurs. It is indicated that endothelial dysfunction induced by DES plays a critical role in neoatherosclerotic development. Upregulation of reactive oxygen species (ROS) induced by DES implantation significantly affects endothelial cells healing and functioning, therefore rendering NA formation. In light of the role of ROS in suppression of endothelial healing, combining antioxidant therapies with stenting technology may facilitate reestablishing a functioning endothelium to improve clinical outcome for patients with stenting. Yuanyuan Cui, Yue Liu, Fuhai Zhao, Dazhuo Shi, and Keji Chen Copyright © 2016 Yuanyuan Cui et al. All rights reserved. Antioxidant, Cytotoxic, and Antiproliferative Activities and Total Polyphenol Contents of the Extracts of Geissospermum reticulatum Bark Wed, 29 Jun 2016 11:05:16 +0000 http://www.hindawi.com/journals/omcl/2016/2573580/ Geissospermum species are medically important plants due to their health-promoting effects. The objective of this study was to determine the antioxidant ability and antiproliferative and cytotoxic effects of infusions, tinctures, and ethanolic extracts of Geissospermum reticulatum barks in relation to the contents of total phenolics and flavonoids. Seven samples of barks were collected in various regions of Peruvian Amazonia. We found that the amount of total phenolics in the studied products varied from 212.40 0.69 to 1253.92 11.20 mg GAE/kg. In our study there is a correlation () between the results of antioxidants assays: FRAP and ORAC for tinctures, infusions, and ethanolic extracts of G. reticulatum barks. We have also observed antiproliferative activities of the ethanolic extracts on normal T-cells. These extracts have caused death on malignant cell lines (THP-1 and HL-60) and this data correlates well with their antioxidant capacity measured by ORAC method. Interestingly, the highest concentration of the ethanolic extract was not toxic in the zebrafish embryo developmental assay. Our results indicate that G. reticulatum is rich in antioxidants and have cytotoxic and antiproliferative properties. The data suggests potential immunosuppressive role of the extracts. This is the first study presenting the results of chemical and biological analysis of multiple preparations from G. reticulatum. Joanna J. Sajkowska-Kozielewicz, Paweł Kozielewicz, Nicholas M. Barnes, Iwona Wawer, and Katarzyna Paradowska Copyright © 2016 Joanna J. Sajkowska-Kozielewicz et al. All rights reserved. Identification of Redox and Glucose-Dependent Txnip Protein Interactions Wed, 29 Jun 2016 08:55:09 +0000 http://www.hindawi.com/journals/omcl/2016/5829063/ Thioredoxin-interacting protein (Txnip) acts as a negative regulator of thioredoxin function and is a critical modulator of several diseases including, but not limited to, diabetes, ischemia-reperfusion cardiac injury, and carcinogenesis. Therefore, Txnip has become an attractive therapeutic target to alleviate disease pathologies. Although Txnip has been implicated with numerous cellular processes such as proliferation, fatty acid and glucose metabolism, inflammation, and apoptosis, the molecular mechanisms underlying these processes are largely unknown. The objective of these studies was to identify Txnip interacting proteins using the proximity-based labeling method, BioID, to understand differential regulation of pleiotropic Txnip cellular functions. The BioID transgene fused to Txnip expressed in HEK293 identified 31 interacting proteins. Many protein interactions were redox-dependent and were disrupted through mutation of a previously described reactive cysteine (C247S). Furthermore, we demonstrate that this model can be used to identify dynamic Txnip interactions due to known physiological regulators such as hyperglycemia. These data identify novel Txnip protein interactions and demonstrate dynamic interactions dependent on redox and glucose perturbations, providing clarification to the pleiotropic cellular functions of Txnip. Benjamin J. Forred, Skyla Neuharth, Dae In Kim, Michael W. Amolins, Khatereh Motamedchaboki, Kyle J. Roux, and Peter F. Vitiello Copyright © 2016 Benjamin J. Forred et al. All rights reserved. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model Tue, 28 Jun 2016 15:27:59 +0000 http://www.hindawi.com/journals/omcl/2016/7453849/ Purpose. To investigate the preventive effect of resveratrol (RES) on the formation of portal vein system thrombosis (PVST) in a rat fibrosis model. Methods. A total of 64 male SD rats, weighing 200–300 g, were divided into five groups: Sham operation, Splenectomy I, Splenectomy II, RES, and low molecular weight heparin (LMWH), with the former two groups as nonfibrosis controls. Blood samples were subjected to biochemical assays. Platelet apoptosis was measured by flow cytometry. All rats were euthanized for PVST detection one week after operation. Results. No PVST occurred in nonfibrosis controls. Compared to Splenectomy II, the incidences of PVST in RES and LMWH groups were significantly decreased (both ). Two rats in LMWH group died before euthanasia due to intra-abdominal hemorrhage. In RES group, significant decreases in platelet aggregation, platelet radical oxygen species (ROS) production, and increase in platelet nitric oxide (NO) synthesis and platelet apoptosis were observed when compared with Splenectomy II (all ), while in LMWH group only significant decrease in platelet aggregation was observed. Conclusion. Prophylactic application of RES could safely reduce the incidence of PVST after splenectomy in cirrhotic rat. Regulation of platelet function and induction of platelet apoptosis might be the underlying mechanisms. Meng Xu, Wanli Xue, Zhenhua Ma, Jigang Bai, and Shengli Wu Copyright © 2016 Meng Xu et al. All rights reserved. Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction Tue, 28 Jun 2016 10:59:38 +0000 http://www.hindawi.com/journals/omcl/2016/7598294/ Purpose. We evaluated the effect of sulforaphane (SFN) treatment on the function and changes of expression of Nrf2-ARE pathway in the bladder of rats with bladder outlet obstruction (BOO). Materials and Methods. A total of 18 male Sprague-Dawley rats at age of 8 weeks were divided into 3 groups (6 of each): the sham operated group, the BOO group, and the BOO+SFN group. We examined histological alterations and the changes of oxidative stress markers and the protein expression of the Nrf2-ARE pathway. Results. We found that SFN treatment could prolong micturition interval and increase bladder capacity and bladder compliance. However, the peak voiding pressure was lower than BOO group. SFN treatment can ameliorate the increase of collagen fibers induced by obstruction. SFN treatment also increased the activity of SOD, GSH-Px, and CAT compared to the other groups. The level of bladder cell apoptosis was decreased in BOO rats with SFN treatment. Moreover, SFN could reduce the ratio of Bax/Bcl-2 expression. Furthermore, SFN could activate the Nrf2 expression with elevation of its target antioxidant proteins. Conclusions. The sulforaphane-mediated decrease of oxidative stress and activation of the Nrf2-ARE pathway may ameliorate bladder dysfunction caused by bladder outlet obstruction. Chong Liu, Huan Xu, Shi Fu, Yanbo Chen, Qi Chen, Zhikang Cai, Juan Zhou, and Zhong Wang Copyright © 2016 Chong Liu et al. All rights reserved. Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide Tue, 28 Jun 2016 10:50:09 +0000 http://www.hindawi.com/journals/omcl/2016/5190314/ Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide. Wei Li, Lun Zhang, Xin Chen, Zhengdong Jiang, Liang Zong, and Qingyong Ma Copyright © 2016 Wei Li et al. All rights reserved. The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBPβ rather than Enterotoxigenic Bacteroides fragilis Infection Tue, 28 Jun 2016 10:07:12 +0000 http://www.hindawi.com/journals/omcl/2016/2353560/ Colorectal cancer is one of the most common cancers in the world. It is well known that the chronic inflammation can promote the progression of colorectal cancer (CRC). Recently, a number of studies revealed a potential association between colorectal inflammation, cancer progression, and infection caused by enterotoxigenic Bacteroides fragilis (ETBF). Bacterial enterotoxin activates spermine oxidase (SMO), which produces spermidine and H2O2 as byproducts of polyamine catabolism, which, in turn, enhances inflammation and tissue injury. Using qPCR analysis, we estimated the expression of SMOX gene and ETBF colonization in CRC patients. We found no statistically significant associations between them. Then we selected genes involved in polyamine metabolism, metabolic reprogramming, and inflammation regulation and estimated their expression in CRC. We observed overexpression of SMOX, ODC1, SRM, SMS, MTAP, c-Myc, C/EBPβ (CREBP), and other genes. We found that two mediators of metabolic reprogramming, inflammation, and cell proliferation c-Myc and C/EBPβ may serve as regulators of polyamine metabolism genes (SMOX, AZIN1, MTAP, SRM, ODC1, AMD1, and AGMAT) as they are overexpressed in tumors, have binding site according to ENCODE ChIP-Seq data, and demonstrate strong coexpression with their targets. Thus, increased polyamine metabolism in CRC could be driven by c-Myc and C/EBPβ rather than ETBF infection. Anastasiya V. Snezhkina, George S. Krasnov, Anastasiya V. Lipatova, Asiya F. Sadritdinova, Olga L. Kardymon, Maria S. Fedorova, Nataliya V. Melnikova, Oleg A. Stepanov, Andrew R. Zaretsky, Andrey D. Kaprin, Boris Y. Alekseev, Alexey A. Dmitriev, and Anna V. Kudryavtseva Copyright © 2016 Anastasiya V. Snezhkina et al. All rights reserved. The Role of Omega-3 Polyunsaturated Fatty Acids in Stroke Tue, 28 Jun 2016 09:49:11 +0000 http://www.hindawi.com/journals/omcl/2016/6906712/ Stroke is the third commonest cause of death following cardiovascular diseases and cancer. In particular, in recent years, the morbidity and mortality of stroke keep remarkable growing. However, stroke still captures people attention far less than cardiovascular diseases and cancer. Past studies have shown that oxidative stress and inflammation play crucial roles in the progress of cerebral injury induced by stroke. Evidence is accumulating that the dietary supplementation of fish oil exhibits beneficial effects on several diseases, such as cardiovascular diseases, metabolic diseases, and cancer. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), the major component of fish oil, have been found against oxidative stress and inflammation in cardiovascular diseases. And the potential of n-3 PUFAs in stroke treatment is attracting more and more attention. In this review, we will review the effects of n-3 PUFAs on stroke and mainly focus on the antioxidant and anti-inflammatory effects of n-3 PUFAs. Jiyuan Bu, Yang Dou, Xiaodi Tian, Zhong Wang, and Gang Chen Copyright © 2016 Jiyuan Bu et al. All rights reserved. Serum Oxidized LDL Levels in Type 2 Diabetic Patients with Retinopathy in Mthatha Region of the Eastern Cape Province of South Africa Tue, 28 Jun 2016 09:16:36 +0000 http://www.hindawi.com/journals/omcl/2016/2063103/ Oxidized low-density lipoprotein (ox-LDL) is a powerful natural prooxidant derived from native LDL by cell-mediated oxidation. Such oxidation occurs more easily in glycated LDL as observed in diabetes mellitus. We evaluated and compared selected biomarkers of oxidative stress and total antioxidant (TAO) levels in type 2 diabetes mellitus (T2DM) patients with and without retinopathy in the Mthatha region of the Eastern Cape Province, South Africa. The participants totaled to 140 and this number comprised 98 diabetic patients on treatment, stratified by diabetes (54) and diabetes with retinopathy (44). Forty-two nondiabetic healthy controls made up the 140. Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), lipid profile, serum ox-LDL, thiobarbituric acid reactive substances (TBARS), and TAO levels were measured. A statistically significant increase in FPG, HbA1c, TBARS, and ox-LDL and a significant decrease in TAO levels were seen in T2DM patients with retinopathy as compared to controls. A significant negative correlation was observed between TAO and ox-LDL levels in the diabetic group. In multiple linear regression analyses, duration of diabetes, triglyceride, TAO, and LDL cholesterol were found to be significantly associated with ox-LDL. In multiple logistic regression analyses, ox-LDL [OR 1.02 (1.01–1.03), ] was the only risk factor and was significantly associated with the presence of retinopathy. Farzana Ganjifrockwala, Jim Joseph, and Grace George Copyright © 2016 Farzana Ganjifrockwala et al. All rights reserved.