Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Euterpe edulis Extract but Not Oil Enhances Antioxidant Defenses and Protects against Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet in Rats Thu, 23 Jun 2016 14:55:09 +0000 http://www.hindawi.com/journals/omcl/2016/8173876/ We investigated the effects of E. edulis bioproducts (lyophilized pulp [LEE], defatted lyophilized pulp [LDEE], and oil [EO]) on nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in rats. All products were chemically analyzed. In vivo, 42 rats were equally randomized into seven groups receiving standard diet, HFD alone or combined with EO, LEE, or LDEE. After NAFLD induction, LEE, LDEE, or EO was added to the animals’ diet for 4 weeks. LEE was rich in polyunsaturated fatty acids. From LEE degreasing, LDEE presented higher levels of anthocyanins and antioxidant capacity in vitro. Dietary intake of LEE and especially LDEE, but not EO, attenuated diet-induced NAFLD, reducing inflammatory infiltrate, steatosis, and lipid peroxidation in liver tissue. Although both E. edulis bioproducts were not hepatotoxic, only LDEE presented sufficient benefits to treat NAFLD in rats, possibly by its low lipid content and high amount of phenols and anthocyanins. Rodrigo Barros Freitas, Rômulo Dias Novaes, Reggiani Vilela Gonçalves, Bianca Gazolla Mendonça, Eliziária Cardoso Santos, Andréia Queiroz Ribeiro, Luciana Moreira Lima, Luciano Gomes Fietto, Maria do Carmo Gouveia Peluzio, and João Paulo Viana Leite Copyright © 2016 Rodrigo Barros Freitas et al. All rights reserved. Chronic Alcohol Intoxication and Cortical Ischemia: Study of Their Comorbidity and the Protective Effects of Minocycline Wed, 22 Jun 2016 09:04:44 +0000 http://www.hindawi.com/journals/omcl/2016/1341453/ Chronic alcohol intoxication (CAI) increases both morbidity and mortality of stroke patients. Despite the high prevalence of CAI and ischemic stroke, studies addressing their comorbidity and/or protective alternatives remain scarce. Thus, the influence of CAI on both stroke outcome and minocycline treatment (recognized for its neuroprotective effect) was investigated. Female Wistar rats (35 days old) were treated with water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days. Then, focal ischemia was induced by endothelin-1 in the motor cortex. Two hours later, four doses of 50 mg/kg of minocycline every 12 hours followed by five doses of 25 mg/kg every 24 hours were administered. Behavioral performance (open field and rotarod tests) and immunohistochemical (cellular density, neuronal death, and astrocytic activation) and biochemical (lipid peroxidation and nitrite levels) analyses were performed. CAI increased motor disruption, nitrite and lipid peroxidation levels, and neuronal loss caused by ischemia, whereas it reduced the astrogliosis. Minocycline was effective in preventing the motor and tissue damage caused by stroke. However, these effects were attenuated when CAI preceded stroke. Our data suggest that CAI beginning in adolescence contributes to a worse outcome in ischemic stroke survivors and reduces the benefits of minocycline, possibly requiring adjustments in therapy. Enéas Andrade Fontes-Júnior, Cristiane Socorro Ferraz Maia, Luanna Melo Pereira Fernandes, Walace Gomes-Leal, Allan Costa-Malaquias, Rafael Rodrigues Lima, Rui Daniel Prediger, and Maria Elena Crespo-López Copyright © 2016 Enéas Andrade Fontes-Júnior et al. All rights reserved. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy Tue, 21 Jun 2016 14:15:43 +0000 http://www.hindawi.com/journals/omcl/2016/6235641/ Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy. Barbara Marengo, Mariapaola Nitti, Anna Lisa Furfaro, Renata Colla, Chiara De Ciucis, Umberto Maria Marinari, Maria Adelaide Pronzato, Nicola Traverso, and Cinzia Domenicotti Copyright © 2016 Barbara Marengo et al. All rights reserved. Biological Activities of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside in Antiaging and Antiaging-Related Disease Treatments Mon, 20 Jun 2016 11:42:21 +0000 http://www.hindawi.com/journals/omcl/2016/4973239/ 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is active component of the Chinese medicinal plant Polygonum multiflorum Thunb. (THSG). Pharmacological studies have demonstrated that THSG exhibits numerous biological functions in treating atherosclerosis, lipid metabolism, vascular and cardiac remodeling, vascular fibrosis, cardiac-cerebral ischemia, learning and memory disorders, neuroinflammation, Alzheimer and Parkinson diseases, diabetic complications, hair growth problems, and numerous other conditions. This review focuses on the biological effects of THSG in antiaging and antiaging-related disease treatments and discusses its molecular mechanisms. Shuang Ling and Jin-Wen Xu Copyright © 2016 Shuang Ling and Jin-Wen Xu. All rights reserved. Physiological Importance of Hydrogen Sulfide: Emerging Potent Neuroprotector and Neuromodulator Mon, 20 Jun 2016 08:32:53 +0000 http://www.hindawi.com/journals/omcl/2016/9049782/ Hydrogen sulfide (H2S) is an emerging neuromodulator that is considered to be a gasotransmitter similar to nitrogen oxide (NO) and carbon monoxide (CO). H2S exerts universal cytoprotective effects and acts as a defense mechanism in organisms ranging from bacteria to mammals. It is produced by the enzymes cystathionine β-synthase (CBS), cystathionine ϒ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (MST), and D-amino acid oxidase (DAO), which are also involved in tissue-specific biochemical pathways for H2S production in the human body. H2S exerts a wide range of pathological and physiological functions in the human body, from endocrine system and cellular longevity to hepatic protection and kidney function. Previous studies have shown that H2S plays important roles in peripheral nerve regeneration and degeneration and has significant value during Schwann cell dedifferentiation and proliferation but it is also associated with axonal degradation and the remyelination of Schwann cells. To date, physiological and toxic levels of H2S in the human body remain unclear and most of the mechanisms of action underlying the effects of H2S have yet to be fully elucidated. The primary purpose of this review was to provide an overview of the role of H2S in the human body and to describe its beneficial effects. Sandesh Panthi, Hyung-Joo Chung, Junyang Jung, and Na Young Jeong Copyright © 2016 Sandesh Panthi et al. All rights reserved. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis Mon, 20 Jun 2016 06:29:00 +0000 http://www.hindawi.com/journals/omcl/2016/5806057/ Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis. Yijun Zheng and Duming Zhu Copyright © 2016 Yijun Zheng and Duming Zhu. All rights reserved. In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice Sun, 19 Jun 2016 11:52:44 +0000 http://www.hindawi.com/journals/omcl/2016/6797851/ This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5. María del Carmen García-Rodríguez, Lourdes Montserrat Hernández-Cortés, and Mario Agustín Altamirano-Lozano Copyright © 2016 María del Carmen García-Rodríguez et al. All rights reserved. Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice Sun, 19 Jun 2016 10:56:55 +0000 http://www.hindawi.com/journals/omcl/2016/2715718/ Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury. Dongdong Wu, Biao Gao, Mengling Li, Ling Yao, Shuaiwei Wang, Mingliang Chen, Hui Li, Chunyan Ma, Ailing Ji, and Yanzhang Li Copyright © 2016 Dongdong Wu et al. All rights reserved. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology Thu, 16 Jun 2016 11:49:09 +0000 http://www.hindawi.com/journals/omcl/2016/2989076/ Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. Ryan A. Denu and Peiman Hematti Copyright © 2016 Ryan A. Denu and Peiman Hematti. All rights reserved. Effects of Synthetic Serum Supplementation in Sperm Preparation Media on Sperm Capacitation and Function Test Results Thu, 16 Jun 2016 11:33:06 +0000 http://www.hindawi.com/journals/omcl/2016/1027158/ Albumin supplementation of culture media induces sperm capacitation in assisted reproduction technique cycles. Synthetic serum supplementation is clinically used to replace albumin for preventing transmission of infectious agents. However, the effects of synthetic serum supplementation on sperm capacitation have rarely been investigated. Spermatozoa from 30 men with normal basic semen analysis results were collected, divided into five aliquots, and cultured in capacitating conditions in four combinations of two synthetic serum supplements, serum substitute supplement (SSS) and serum protein substitute (SPS), and two fertilization media, Quinns Advantage™ Fertilization (QF) and human tubular fluid (HTF) media. Reactive oxygen species (ROS) levels in spermatozoa were measured through chemiluminescence. Furthermore, acrosome reaction and western blotting for tyrosine phosphorylation were used to evaluate sperm capacitation. HTF+SSS had significantly higher ROS levels than QF+SPS did (11,725 ± 1,172 versus 6,278 ± 864 relative light units). In addition, the spermatozoa cultured in QF+SPS had lower motility, acrosome reaction rates, and tyrosine phosphorylation levels compared with those cultured in HTF+SSS. In conclusion, the effects of synthetic serum supplementation on sperm capacitation varied according to the combination of media. These differences may lead to variations in spermatozoon ROS levels, thus affecting sperm function test results. Ying-Fu Shih, Shu-Ling Tzeng, Wen-Jung Chen, Chun-Chia Huang, Hsiu-Hui Chen, Tsung-Hsien Lee, and Maw-Sheng Lee Copyright © 2016 Ying-Fu Shih et al. All rights reserved. Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury Wed, 15 Jun 2016 10:59:29 +0000 http://www.hindawi.com/journals/omcl/2016/4298945/ Background and Aims. Human embryonic stem cell- (hESC-) derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP) in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days) and then on more differentiated cardiomyocytes (6 + 24 days), both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) (10−7, 10−6, and 10−5 M), BNP (10−9, 10−8, and 10−7 M), and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10−5 M). Results. SNAP (10−6, 10−5 M) significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10−6 M) also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms. János Pálóczi, Zoltán V. Varga, Ágota Apáti, Kornélia Szebényi, Balázs Sarkadi, Rosalinda Madonna, Raffaele De Caterina, Tamás Csont, Thomas Eschenhagen, Péter Ferdinandy, and Anikó Görbe Copyright © 2016 János Pálóczi et al. All rights reserved. Oxidative Stress Related Diseases in Newborns Wed, 15 Jun 2016 09:40:45 +0000 http://www.hindawi.com/journals/omcl/2016/2768365/ We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. Yasemin Ozsurekci and Kubra Aykac Copyright © 2016 Yasemin Ozsurekci and Kubra Aykac. All rights reserved. Current Antioxidant Treatments in Organ Transplantation Wed, 15 Jun 2016 08:59:00 +0000 http://www.hindawi.com/journals/omcl/2016/8678510/ Oxidative stress is one of the key mechanisms affecting the outcome throughout the course of organ transplantation. It is widely believed that the redox balance is dysregulated during ischemia and reperfusion (I/R) and causes subsequent oxidative injury, resulting from the formation of reactive oxygen species (ROS). Moreover, in order to alleviate organ shortage, increasing number of grafts is retrieved from fatty, older, and even non-heart-beating donors that are particularly vulnerable to the accumulation of ROS. To improve the viability of grafts and reduce the risk of posttransplant dysfunction, a large number of studies have been done focusing on the antioxidant treatments for the purpose of maintaining the redox balance and thereby protecting the grafts. This review provides an overview of these emerging antioxidant treatments, targeting donor, graft preservation, and recipient as well. Shaojun Shi and Feng Xue Copyright © 2016 Shaojun Shi and Feng Xue. All rights reserved. Biofunctional Activities of Equisetum ramosissimum Extract: Protective Effects against Oxidation, Melanoma, and Melanogenesis Wed, 15 Jun 2016 08:53:35 +0000 http://www.hindawi.com/journals/omcl/2016/2853543/ Equisetum ramosissimum, a genus of Equisetaceae, is a medicinal plant that can be separated into ethyl acetate (EA), dichloromethane (DM), n-hexane (Hex), methanol (MeOH), and water extracts. EA extract was known to have potent antioxidative properties, reducing power, DPPH scavenging activity, and metal ion chelating activity. This study compared these five extracts in terms of their inhibiting effects on three human malignant melanomas: A375, A375.S2, and A2058. MTT assay presented the notion that both EA and DM extracts inhibited melanoma growth but did not affect the viabilities of normal dermal keratinocytes (HaCaT) or fibroblasts. Western blot analyses showed that both EA and DM extracts induced overexpression of caspase proteins in all three melanomas. To determine their roles in melanogenesis, this study analyzed their in vitro suppressive effects on mushroom tyrosinase. All extracts except for water revealed moderate suppressive effects. None of the extracts affected B16-F10 cells proliferation. EA extract inhibited cellular melanin production whereas DM extract unexpectedly enhanced cellular pigmentation in B16-F10 cells. Data for modulations of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 showed that EA extract inhibited protein expression mentioned above whereas DM extract had the opposite effect. Overall, the experiments indicated that the biofunctional activities of EA extract contained in food and cosmetics protect against oxidation, melanoma, and melanin production. Pin-Hui Li, Yu-Pin Chiu, Chieh-Chih Shih, Zhi-Hong Wen, Laura Kaodichi Ibeto, Shu-Hung Huang, Chien Chih Chiu, Dik-Lung Ma, Chung-Hang Leung, Yaw-Nan Chang, and Hui-Min David Wang Copyright © 2016 Pin-Hui Li et al. All rights reserved. Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway Mon, 13 Jun 2016 06:44:07 +0000 http://www.hindawi.com/journals/omcl/2016/7079487/ Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway. Liu Tongqiang, Liu Shaopeng, Yu Xiaofang, Song Nana, Xu Xialian, Hu Jiachang, Zhang Ting, and Ding Xiaoqiang Copyright © 2016 Liu Tongqiang et al. All rights reserved. Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model Thu, 09 Jun 2016 12:09:40 +0000 http://www.hindawi.com/journals/omcl/2016/5763743/ Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention that could be administered as an alternative to cooling in cases of perinatal hypoxia-ischemia (HI). In the current study we hypothesized that RIPostC in the piglet model of birth asphyxia confers protection by reducing nitrosative stress and subsequent nitrotyrosine formation, as well as having an effect on glial immunoreactivity. Postnatal day 1 (P1) piglets underwent HI brain injury and were randomised to HI (control) or HI + RIPostC. Immunohistochemistry assessment 48 hours after HI revealed a significant decrease in brain nitrotyrosine deposits in the RIPostC-treated group (). This was accompanied by a significant increase in eNOS expression () and decrease in iNOS (), with no alteration in nNOS activity. Interestingly, RIPostC treatment was associated with a significant increase in GFAP () and IBA1 (), markers of astroglial and microglial activity, respectively. The current study demonstrates a beneficial effect of RIPostC therapy in the preclinical piglet model of neonatal asphyxia, which appears to be mediated by modulation of nitrosative stress, despite glial activation. Eridan Rocha-Ferreira, Brogan Rudge, Michael P. Hughes, Ahad A. Rahim, Mariya Hristova, and Nicola J. Robertson Copyright © 2016 Eridan Rocha-Ferreira et al. All rights reserved. Sirtuins and Cancer: Role in the Epithelial-Mesenchymal Transition Thu, 09 Jun 2016 08:19:09 +0000 http://www.hindawi.com/journals/omcl/2016/3031459/ The human sirtuins (SIRT1–SIRT7) enzymes are a highly conserved family of NAD+-dependent histone deacetylases, which play a critical role in the regulation of a large number of metabolic pathways involved in stress response and aging. Cancer is an age-associated disease, and sirtuins may have a considerable impact on a plethora of processes that regulate tumorigenesis. In particular, growing evidence suggests that sirtuins may modulate epithelial plasticity by inducing transcriptional reprogramming leading to epithelial-mesenchymal transition (EMT), invasion, and metastases. Though commonly regarded as EMT inducers, sirtuins may also suppress this process, and their functional properties seem to largely depend on the cellular context, stage of cancer development, tissue of origin, and microenvironment architecture. Here, we review the role of sirtuins in cancer biology with particular emphasis on their role in EMT. Raffaele Palmirotta, Mauro Cives, David Della-Morte, Barbara Capuani, Davide Lauro, Fiorella Guadagni, and Franco Silvestris Copyright © 2016 Raffaele Palmirotta et al. All rights reserved. Diagnostic, Prognostic, and Therapeutic Value of Circulating miRNAs in Heart Failure Patients Associated with Oxidative Stress Thu, 09 Jun 2016 06:21:39 +0000 http://www.hindawi.com/journals/omcl/2016/5893064/ Heart failure is a major public health problem especially in the aging population (≥65 years old), affecting nearly 5 million Americans and 15 million European people. Effective management of heart failure (HF) depends on a correct and rapid diagnosis. Presently, BNP (brain natriuretic peptide) or N-terminal pro-brain natriuretic peptide (NT-proBNP) assay is generally accepted by the international community for diagnostic evaluation and risk stratification of patients with HF. However, regardless of its widespread clinical use, BNP is still encumbered by reduced specificity. As a result, diagnosis of heart failure remains challenging. Although significant improvement happened in the clinical management of HF over the last 2 decades, traditional treatments are ultimately ineffective in many patients who progress to advanced HF. Therefore, a novel diagnostic, prognostic biomarker and new therapeutic approach are required for clinical management of HF patients. Circulating miRNAs seem to be the right choice for novel noninvasive biomarkers as well as new treatment strategies for HF. In this review, we briefly discuss the diagnostic, prognostic, and therapeutic role of circulating miRNAs in heart failure patients. We also mentioned our own technique of extraction of RNA and detection of circulating miRNAs from human plasma and oxidative stress associated miRNAs with HF. Md Sayed Ali Sheikh, Umme Salma, Baohai Zhang, Jimei Chen, Jian Zhuang, and Zhu Ping Copyright © 2016 Md Sayed Ali Sheikh et al. All rights reserved. Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications Wed, 08 Jun 2016 11:04:03 +0000 http://www.hindawi.com/journals/omcl/2016/1908164/ Lung cancer has a very high mortality-to-incidence ratio, representing one of the main causes of cancer mortality worldwide. Therefore, new treatment strategies are urgently needed. Several diseases including lung cancer have been associated with the action of reactive oxygen species (ROS) from which hydrogen peroxide (H2O2) is one of the most studied. Despite the fact that H2O2 may have opposite effects on cell proliferation depending on the concentration and cell type, it triggers several antiproliferative responses. H2O2 produces both nuclear and mitochondrial DNA lesions, increases the expression of cell adhesion molecules, and increases p53 activity and other transcription factors orchestrating cancer cell death. In addition, H2O2 facilitates the endocytosis of oligonucleotides, affects membrane proteins, induces calcium release, and decreases cancer cell migration and invasion. Furthermore, the MAPK pathway and the expression of genes related to inflammation including interleukins, TNF-α, and NF-κB are also affected by H2O2. Herein, we will summarize the main effects of hydrogen peroxide on human lung cancer leading to suggesting it as a potential therapeutic tool to fight this disease. Because of the multimechanistic nature of this molecule, novel therapeutic approaches for lung cancer based on the use of H2O2 may help to decrease the mortality from this malignancy. Gabriela Vilema-Enríquez, Aurora Arroyo, Marcelo Grijalva, Ricardo Israel Amador-Zafra, and Javier Camacho Copyright © 2016 Gabriela Vilema-Enríquez et al. All rights reserved. Lipoxin A4 Preconditioning Attenuates Intestinal Ischemia Reperfusion Injury through Keap1/Nrf2 Pathway in a Lipoxin A4 Receptor Independent Manner Tue, 07 Jun 2016 11:09:31 +0000 http://www.hindawi.com/journals/omcl/2016/9303606/ Oxidative stress plays a critical role in the pathogenesis of intestinal ischemia reperfusion (IIR) injury. Enhancement in endogenous Lipoxin A4 (LXA4), a potent antioxidant and mediator, is associated with attenuation of IIR. However, the effects of LXA4 on IIR injury and the potential mechanisms are unknown. In a rat IIR (ischemia 45 minutes and subsequent reperfusion 6 hours) model, IIR caused intestinal injury, evidenced by increased serum diamine oxidase, D-lactic acid, intestinal-type fatty acid-binding protein, and the oxidative stress marker 15-F2t-Isoprostane. LXA4 treatment significantly attenuated IIR injury by reducing mucosal 15-F2t-Isoprostane and elevating endogenous antioxidant superoxide dismutase activity, accompanied with Keap1/Nrf2 pathway activation. Meanwhile, LXA4 receptor antagonist Boc-2 reversed the protective effects of LXA4 on intestinal injury but failed to affect the oxidative stress and the related Nrf2 pathway. Furthermore, Nrf2 antagonist brusatol reversed the antioxidant effects conferred by LXA4 and led to exacerbation of intestinal epithelium cells oxidative stress and apoptosis, finally resulting in a decrease of survival rate of rat. Meanwhile, LXA4 pretreatment upregulated nuclear Nrf2 level and reduced hypoxia/reoxygenation-induced IEC-6 cell damage and Nrf2 siRNA reversed this protective effect of LXA4 in vitro. In conclusion, these findings suggest that LXA4 ameliorates IIR injury by activating Keap1/Nrf2 pathway in a LXA4 receptor independent manner. Xue Han, Weifeng Yao, Zipeng Liu, Haobo Li, Zhong-jun Zhang, Ziqing Hei, and Zhengyuan Xia Copyright © 2016 Xue Han et al. All rights reserved. Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury Thu, 02 Jun 2016 12:57:33 +0000 http://www.hindawi.com/journals/omcl/2016/8235921/ Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms. Kassiani Theodoraki, Iosifina Karmaniolou, Aliki Tympa, Marios-Konstantinos Tasoulis, Constantinos Nastos, Ioannis Vassiliou, Nikolaos Arkadopoulos, and Vassilios Smyrniotis Copyright © 2016 Kassiani Theodoraki et al. All rights reserved. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line Thu, 02 Jun 2016 09:54:06 +0000 http://www.hindawi.com/journals/omcl/2016/1735841/ Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS) levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders. Hirotaka Yamamoto, Katsutaro Morino, Lemecha Mengistu, Taishi Ishibashi, Kohei Kiriyama, Takao Ikami, and Hiroshi Maegawa Copyright © 2016 Hirotaka Yamamoto et al. All rights reserved. NRF2, a Key Regulator of Antioxidants with Two Faces towards Cancer Thu, 02 Jun 2016 09:37:38 +0000 http://www.hindawi.com/journals/omcl/2016/2746457/ While reactive oxygen species (ROS) is generally considered harmful, a relevant amount of ROS is necessary for a number of cellular functions, including the intracellular signal transduction. In order to deal with an excessive amount of ROS, organisms are equipped with a sufficient amount of antioxidants together with NF-E2-related factor-2 (NRF2), a transcription factor that plays a key role in the protection of organisms against environmental or intracellular stresses. While the NRF2 activity has been generally viewed as beneficial to preserve the integrity of organisms, recent studies have demonstrated that cancer cells hijack the NRF2 activity to survive under the oxidative stress and, therefore, a close check must be kept on the NRF2 activity in cancer. In the present review, we briefly highlight important progresses in understanding the molecular mechanism, structure, and function of KEAP1 and NRF2 interaction. In addition, we provide general perspectives that justify conflicting views on the NRF2 activity in cancer. Jaieun Kim and Young-Sam Keum Copyright © 2016 Jaieun Kim and Young-Sam Keum. All rights reserved. Cigarette Smoke Extract-Induced Oxidative Stress and Fibrosis-Related Genes Expression in Orbital Fibroblasts from Patients with Graves’ Ophthalmopathy Thu, 02 Jun 2016 08:15:26 +0000 http://www.hindawi.com/journals/omcl/2016/4676289/ Cigarette smoking is the most important risk factor for the development or deterioration of Graves’ ophthalmopathy. Smoke-induced increased generation of reactive oxygen species may be involved. However, it remains to be clarified how orbital fibroblasts are affected by cigarette smoking. Our study demonstrated that Graves’ orbital fibroblasts have exaggerated response to cigarette smoke extract challenge along with increased oxidative stress, fibrosis-related genes expression, especially connective tissue growth factor, and intracellular levels of transforming growth factor-β1 and interleukin-1β. The findings obtained in this study provide some clues for the impact of cigarette smoking on Graves’ ophthalmopathy and offer a theoretical basis for the potential and rational use of antioxidants in treating Graves’ ophthalmopathy. Hui-Chuan Kau, Shi-Bei Wu, Chieh-Chih Tsai, Catherine Jui-Ling Liu, and Yau-Huei Wei Copyright © 2016 Hui-Chuan Kau et al. All rights reserved. “Inflammaging” as a Druggable Target: A Senescence-Associated Secretory Phenotype—Centered View of Type 2 Diabetes Wed, 01 Jun 2016 10:55:17 +0000 http://www.hindawi.com/journals/omcl/2016/1810327/ Aging is a complex phenomenon driven by a variety of molecular alterations. A relevant feature of aging is chronic low-grade inflammation, termed “inflammaging.” In type 2 diabetes mellitus (T2DM), many elements of aging appear earlier or are overrepresented, including consistent inflammaging. T2DM patients have an increased death rate, associated with an incremented inflammatory score. The source of this inflammation is debated. Recently, the senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammaging in both aging and T2DM. Different pathogenic mechanisms linked to T2DM progression and complications development have been linked to senescence and SASP, that is, oxidative stress and endoplasmic reticulum (ER) stress. Here we review the latest data connecting oxidative and ER stress with the SASP in the context of aging and T2DM, with emphasis on endothelial cells (ECs) and endothelial dysfunction. Moreover, since current medical practice is insufficient to completely suppress the increased death rate of diabetic patients, we propose a SASP-centered view of T2DM as a futuristic therapeutic option, possibly opening new prospects by moving the attention from one-organ studies of diabetes complications to a wider targeting of the aging process. Francesco Prattichizzo, Valeria De Nigris, Lucia La Sala, Antonio Domenico Procopio, Fabiola Olivieri, and Antonio Ceriello Copyright © 2016 Francesco Prattichizzo et al. All rights reserved. Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells Tue, 31 May 2016 07:04:37 +0000 http://www.hindawi.com/journals/omcl/2016/2915382/ Oxysterol like 27-hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx) affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells. Yonghae Son, Bo-Young Kim, Seong-Kug Eo, Young Chul Park, and Koanhoi Kim Copyright © 2016 Yonghae Son et al. All rights reserved. Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis Tue, 31 May 2016 06:34:35 +0000 http://www.hindawi.com/journals/omcl/2016/8962763/ The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, ) and RA patients (). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α () (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ ); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher () advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher () AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 () and G3 ( and , resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92. Neide Tomimura Costa, Tatiana Mayumi Veiga Iriyoda, Ana Paula Kallaur, Francieli Delongui, Daniela Frizon Alfieri, Marcell Alysson Batisti Lozovoy, Ricardo Braga Amin, Vinicius Daher Alvares Delfino, Isaias Dichi, and Andréa Name Colado Simão Copyright © 2016 Neide Tomimura Costa et al. All rights reserved. A Genetic Biomarker of Oxidative Stress, the Paraoxonase-1 Q192R Gene Variant, Associates with Cardiomyopathy in CKD: A Longitudinal Study Mon, 30 May 2016 14:26:06 +0000 http://www.hindawi.com/journals/omcl/2016/1507270/ Background. Oxidative stress is a hallmark of CKD and this alteration is strongly implicated in LV hypertrophy and in LV dysfunction. Methods and Patients. We resorted to the strongest genetic biomarker of paraoxonase-1 (PON1) activity, the Q192R variant in the PON1 gene, to unbiasedly assess (Mendelian randomization) the cross-sectional and longitudinal association of this gene-variant with LV mass and function in 206 CKD patients with a 3-year follow-up. Results. The R allele of Q192R polymorphism associated with oxidative stress as assessed by plasma 8-isoPGF2α () and was dose-dependently related in a direct fashion to LVMI (QQ: 131.4 ± 42.6 g/m2; RQ: 147.7 ± 51.1 g/m2; RR: 167.3 ± 41.9 g/m2; ) and in an inverse fashion to systolic function (LV Ejection Fraction) (QQ: 79 ± 12%; RQ: 69 ± 9%; RR: 65 ± 10% ). On longitudinal observation, this gene variant associated with the evolution of the same echocardiographic indicators [LVMI: 13.40 g/m2 per risk allele, ; LVEF: −2.96% per risk allele, ]. Multivariate analyses did not modify these associations. Conclusion. In CKD patients, the R allele of the Q192R variant in the PON1 gene is dose-dependently related to the severity of LVH and LV dysfunction and associates with the longitudinal evolution of these cardiac alterations. These results are compatible with the hypothesis that oxidative stress is implicated in cardiomyopathy in CKD patients. E. Dounousi, I. Bouba, B. Spoto, K. Pappas, G. Tripepi, I. Georgiou, A. Tselepis, M. Elisaf, D. Tsakiris, C. Zoccali, and K. Siamopoulos Copyright © 2016 E. Dounousi et al. All rights reserved. GST-TAT-SOD: Cell Permeable Bifunctional Antioxidant Enzyme—A Potential Selective Radioprotector Mon, 30 May 2016 14:06:17 +0000 http://www.hindawi.com/journals/omcl/2016/5935080/ Superoxide dismutase (SOD) fusion of TAT was proved to be radioprotective in our previous work. On that basis, a bifunctional recombinant protein which was the fusion of glutathione S-transferase (GST), SOD, and TAT was constructed and named GST-TAT-SOD. Herein we report the investigation of the cytotoxicity, cell-penetrating activity, and in vitro radioprotective effect of GST-TAT-SOD compared with wild SOD, single-function recombinant protein SOD-TAT, and amifostine. We demonstrated that wild SOD had little radioprotective effect on irradiated L-02 and Hep G2 cells while amifostine was protective to both cell lines. SOD-TAT or GST-TAT-SOD pretreatment 3 h prior to radiation protects irradiated normal liver cells against radiation damage by eliminating intracellular excrescent superoxide, reducing cellular MDA level, enhancing cellular antioxidant ability and colony formation ability, and reducing apoptosis rate. Compared with SOD-TAT, GST-TAT-SOD was proved to have better protective effect on irradiated normal liver cells and minimal effect on irradiated hepatoma cells. Besides, GST-TAT-SOD was safe for normal cells and effectively transduced into different organs in mice, including the brain. The characteristics of this protein suggest that it may be a potential radioprotective agent in cancer therapy better than amifostine. Fusion of two antioxidant enzymes and cell-penetrating peptides is potentially valuable in the development of radioprotective agent. Jianru Pan, Huocong He, Ying Su, Guangjin Zheng, Junxin Wu, Shutao Liu, and Pingfan Rao Copyright © 2016 Jianru Pan et al. All rights reserved. Impact of Antioxidants on Cardiolipin Oxidation in Liposomes: Why Mitochondrial Cardiolipin Serves as an Apoptotic Signal? Thu, 26 May 2016 10:42:37 +0000 http://www.hindawi.com/journals/omcl/2016/8679469/ Molecules of mitochondrial cardiolipin (CL) get selectively oxidized upon oxidative stress, which triggers the intrinsic apoptotic pathway. In a chemical model most closely resembling the mitochondrial membrane—liposomes of pure bovine heart CL—we compared ubiquinol-10, ubiquinol-6, and alpha-tocopherol, the most widespread naturally occurring antioxidants, with man-made, quinol-based amphiphilic antioxidants. Lipid peroxidation was induced by addition of an azo initiator in the absence and presence of diverse antioxidants, respectively. The kinetics of CL oxidation was monitored via formation of conjugated dienes at 234 nm. We found that natural ubiquinols and ubiquinol-based amphiphilic antioxidants were equally efficient in protecting CL liposomes from peroxidation; the chromanol-based antioxidants, including alpha-tocopherol, were 2-3 times less efficient. Amphiphilic antioxidants, but not natural ubiquinols and alpha-tocopherol, were able, additionally, to protect the CL bilayer from oxidation by acting from the water phase. We suggest that the previously reported therapeutic efficiency of mitochondrially targeted amphiphilic antioxidants is owing to their ability to protect those CL molecules that are inaccessible to natural hydrophobic antioxidants, being trapped within respiratory supercomplexes. The high susceptibility of such occluded CL molecules to oxidation may have prompted their recruitment as apoptotic signaling molecules by nature. Alexey V. Lokhmatikov, Natalia Voskoboynikova, Dmitry A. Cherepanov, Maxim V. Skulachev, Heinz-Jürgen Steinhoff, Vladimir P. Skulachev, and Armen Y. Mulkidjanian Copyright © 2016 Alexey V. Lokhmatikov et al. All rights reserved.