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 in Cancer-Prone Genetic Diseases in Pediatric Age: The Role of Mitochondrial Dysfunction Wed, 27 Apr 2016 13:27:47 +0000 http://www.hindawi.com/journals/omcl/2016/4782426/ Oxidative stress is a distinctive sign in several genetic disorders characterized by cancer predisposition, such as Ataxia-Telangiectasia, Fanconi Anemia, Down syndrome, progeroid syndromes, Beckwith-Wiedemann syndrome, and Costello syndrome. Recent literature unveiled new molecular mechanisms linking oxidative stress to the pathogenesis of these conditions, with particular regard to mitochondrial dysfunction. Since mitochondria are one of the major sites of ROS production as well as one of the major targets of their action, this dysfunction is thought to be the cause of the prooxidant status. Deeper insight of the pathogenesis of the syndromes raises the possibility to identify new possible therapeutic targets. In particular, the use of mitochondrial-targeted agents seems to be an appropriate clinical strategy in order to improve the quality of life and the life span of the patients. Serafina Perrone, Federica Lotti, Ursula Geronzi, Elisa Guidoni, Mariangela Longini, and Giuseppe Buonocore Copyright © 2016 Serafina Perrone et al. All rights reserved. Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat H9c2(2-1) Cardiomyocytes Wed, 27 Apr 2016 09:14:46 +0000 http://www.hindawi.com/journals/omcl/2016/6943053/ This study was aimed at preliminarily assessing the cytoprotective and antioxidative effects of rice bran extracts (RBEs) from a Sarawak local rice variety (local name: “BJLN”) and a commercial rice variety, “MR219,” on oxidative stress in rat H9c2(2-1) cardiomyocytes. The cardiomyocytes were incubated with different concentrations of RBE and hydrogen peroxide (H2O2), respectively, to identify their respective IC50 values and safe dose ranges. Two nonlethal and close-to-IC50 doses of RBE were selected to evaluate their respective effects on H2O2 induced oxidative stress in cardiomyocytes. Both RBEs showed dose-dependent cytotoxicity effects on cardiomyocytes. H2O2 induction of cardiomyocytes pretreated with RBE further revealed the dose-dependent cytoprotective and antioxidative effects of RBE via an increase in IC50 values of H2O2. Preliminary analyses of induction effects of RBE and H2O2 on cellular antioxidant enzyme, catalase (CAT), also revealed their potential in regulating these activities and expression profile of related gene on oxidative stress in cardiomyocytes. Pretreated cardiomyocytes significantly upregulated the enzymatic activity and expression level of CAT under the exposure of H2O2 induced oxidative stress. This preliminary study has demonstrated the potential antioxidant effects of RBE in alleviating H2O2-mediated oxidative injuries via upregulation in enzymatic activities and expression levels of CAT. Xian Wen Tan, Mrinal Bhave, Alan Yean Yip Fong, Eiji Matsuura, Kazuko Kobayashi, Lian Hua Shen, and Siaw San Hwang Copyright © 2016 Xian Wen Tan et al. All rights reserved. Rutin Attenuates Hepatotoxicity in High-Cholesterol-Diet-Fed Rats Wed, 27 Apr 2016 09:05:09 +0000 http://www.hindawi.com/journals/omcl/2016/5436745/ Background and Objective. High-cholesterol diet (HCD) intends to increase the oxidative stress in liver tissues inducing hepatotoxicity. Rutin is a natural flavonoid (vitamin p) which is known to have antioxidative properties. The aim of the present study was to investigate the potential effects of Rutin on hypercholesterolemia-induced hepatotoxicity in rats. Materials and Methods. Male Wistar rats were divided into four groups: G-I control, G-II Rutin, G-III HCD, and G-IV Rutin + HCD. The liver functions and lipid profile were used to evaluate the HCD-induced hepatotoxicity. Quantitative real time-PCR was carried out to evaluate the expression levels of genes in TGF-β/Smad signaling pathway. Results. Rutin in combination with HCD showed a significant protective effect against hepatotoxicity. HCD caused significant increase in the mRNA expression of transforming growth factor beta (TGF-β), Mothers Against Decapentaplegic Homolog 2 (Smad-2), Mothers Against Decapentaplegic Homolog 4 (Smad-4), Bcl-2-binding component 3 (Bbc3), caspase-3, P53 and Interleukin-6 (IL-6) and decrease in the expression levels of Cyclin depended kinase inhibitor (P21) and Interleukin-3 (IL-3) in hepatic cells. Conclusion. TGF-β/Smad signaling pathway is involved in HCD-induced hepatotoxicity and Rutin inhibits the hepatotoxicity via suppressing this pathway. Therefore, Rutin might be considered as a protective agent for hepatotoxicity. Shakir D. AlSharari, Salim S. Al-Rejaie, Hatem M. Abuohashish, Mohamed M. Ahmed, and Mohamed M. Hafez Copyright © 2016 Shakir D. AlSharari et al. All rights reserved. Basal Glutathionylation of Na,K-ATPase α-Subunit Depends on Redox Status of Cells during the Enzyme Biosynthesis Wed, 27 Apr 2016 07:06:05 +0000 http://www.hindawi.com/journals/omcl/2016/9092328/ Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K-ATPase which creates a gradient of sodium and potassium ions. It was found that Na,K-ATPase α-subunit has a basal glutathionylation which is not abrogated by reducing agent. We have shown that acute hypoxia leads to increase of total glutathionylation level of Na,K-ATPase α-subunit; however, basal glutathionylation of α-subunit increases under prolonged hypoxia only. The role of basal glutathionylation in Na,K-ATPase function remains unclear. Understanding significance of basal glutathionylation is complicated by the fact that there are no X-ray structures of Na,K-ATPase with the identified glutathione molecules. We have analyzed all X-ray structures of the Na,K-ATPase α-subunit from pig kidney and found that there are a number of isolated cavities with unresolved electron density close to the relevant cysteine residues. Analysis of the structures showed that this unresolved density in the structure can be occupied by glutathione associated with cysteine residues. Here, we discuss the role of basal glutathionylation of Na,K-ATPase α-subunit and provide evidence supporting the view that this modification is cotranslational. Vladimir A. Mitkevich, Irina Yu. Petrushanko, Yuri M. Poluektov, Ksenia M. Burnysheva, Valentina A. Lakunina, Anastasia A. Anashkina, and Alexander A. Makarov Copyright © 2016 Vladimir A. Mitkevich et al. All rights reserved. Infrared Spectroscopy as a Tool to Study the Antioxidant Activity of Polyphenolic Compounds in Isolated Rat Enterocytes Tue, 26 Apr 2016 13:03:32 +0000 http://www.hindawi.com/journals/omcl/2016/9245150/ The protective effect of different polyphenols, catechin (Cat), quercetin (Qc) (flavonoids), gallic acid (GA), caffeic acid (CfA), chlorogenic acid (ChA) (phenolic acids), and capsaicin (Cap), against H2O2-induced oxidative stress was evaluated in rat enterocytes using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy and Fourier Transform Infrared Microspectroscopy (FTIRM), and results were compared to standard lipid peroxidation techniques: conjugated dienes (CD) and Thiobarbituric Acid Reactive Substances (TBARS). Analysis of ATR-FTIR and FTIRM spectral data allowed the simultaneous evaluation of the effects of H2O2 and polyphenols on lipid and protein oxidation. All polyphenols showed a protective effect against H2O2-induced oxidative stress in enterocytes, when administered before or after H2O2. Cat and capsaicin showed the highest protective effect, while phenolic acids had weaker effects and Qc presented a mild prooxidative effect (IR spectral profile of biomolecules between control and H2O2-treated cells) according to FTIR analyses. These results demonstrated the viability to use infrared spectroscopy to evaluate the oxidant and antioxidant effect of molecules in cell systems assays. Guillermo Barraza-Garza, Hiram Castillo-Michel, Laura A. de la Rosa, Alejandro Martinez-Martinez, Jorge A. Pérez-León, Marine Cotte, and Emilio Alvarez-Parrilla Copyright © 2016 Guillermo Barraza-Garza et al. All rights reserved. Raman Spectroscopic Measurements of Dermal Carotenoids in Breast Cancer Operated Patients Provide Evidence for the Positive Impact of a Dietary Regimen Rich in Fruit and Vegetables on Body Oxidative Stress and BC Prognostic Anthropometric Parameters: A Five-Year Study Tue, 26 Apr 2016 11:02:16 +0000 http://www.hindawi.com/journals/omcl/2016/2727403/ Dermal carotenoids are a feasible marker of the body antioxidative network and may reveal a moderate to severe imbalance of the redox status, thereby providing indication of individual oxidative stress. In this work noninvasive Resonance Raman Spectroscopy (RRS) measurements of skin carotenoids (skin carotenoid score (SCS)) were used to provide indications of individual oxidative stress, each year for five years, in 71 breast cancer (BC) patients at high risk of recurrence. Patients’ SCS has been correlated with parameters relevant to BC risk, waist circumference (WC), and body mass index (BMI), in the aim of monitoring the effect of a dietary regimen intended to positively affect BC risk factors. The RRS methodological approach in BC patients appeared from positive correlation between patients’ SCS and blood level of lycopene. The level of skin carotenoids was inversely correlated with the patients’ WC and BMI. At the end of the 5 y observation BC patients exhibited a significant reduction of WC and BMI and increase of SCS, when strictly adhering to the dietary regimen. In conclusion, noninvasive measurements of skin carotenoids can (i) reveal an oxidative stress condition correlated with parameters of BC risk and (ii) monitor dietary-related variations in BC patients. A. Perrone, A. M. Pintaudi, A. Traina, G. Carruba, A. Attanzio, C. Gentile, L. Tesoriere, and M. A. Livrea Copyright © 2016 A. Perrone et al. All rights reserved. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A Tue, 26 Apr 2016 07:25:49 +0000 http://www.hindawi.com/journals/omcl/2016/5741517/ Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm. Rie Miyata, Naoyuki Tanuma, Hiroshi Sakuma, and Masaharu Hayashi Copyright © 2016 Rie Miyata et al. All rights reserved. The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies Thu, 21 Apr 2016 13:33:08 +0000 http://www.hindawi.com/journals/omcl/2016/8254942/ Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed. Danina M. Muntean, Adrian Sturza, Maria D. Dănilă, Claudia Borza, Oana M. Duicu, and Cristian Mornoș Copyright © 2016 Danina M. Muntean et al. All rights reserved. Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice Thu, 21 Apr 2016 07:50:30 +0000 http://www.hindawi.com/journals/omcl/2016/5380319/ Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin-light chains 1), cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF)), cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB) to nucleus and formation of LC3-II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP-1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy-oxidative stress-inflammation-cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly. Fang Li, Fangfang Lang, Huilin Zhang, Liangdong Xu, Yidan Wang, and Enkui Hao Copyright © 2016 Fang Li et al. All rights reserved. Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice Wed, 20 Apr 2016 13:29:23 +0000 http://www.hindawi.com/journals/omcl/2016/6731093/ Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine1177-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice. Hye Eun Yoon, Eun Nim Kim, Min Young Kim, Ji Hee Lim, In-Ae Jang, Tae Hyun Ban, Seok Joon Shin, Cheol Whee Park, Yoon Sik Chang, and Bum Soon Choi Copyright © 2016 Hye Eun Yoon et al. All rights reserved. Hepatitis C Virus NS5A Protein Triggers Oxidative Stress by Inducing NADPH Oxidases 1 and 4 and Cytochrome P450 2E1 Wed, 20 Apr 2016 12:11:56 +0000 http://www.hindawi.com/journals/omcl/2016/8341937/ Replication of hepatitis C virus (HCV) is associated with the induction of oxidative stress, which is thought to play a major role in various liver pathologies associated with chronic hepatitis C. NS5A protein of the virus is one of the two key viral proteins that are known to trigger production of reactive oxygen species (ROS). To date it has been considered that NS5A induces oxidative stress by altering calcium homeostasis. Herein we show that NS5A-induced oxidative stress was only moderately inhibited by the intracellular calcium chelator BAPTA-AM and not at all inhibited by the drug that blocks the Ca2+ flux from ER to mitochondria. Furthermore, ROS production was not accompanied by induction of ER oxidoreductins (Ero1), H2O2-producing enzymes that are implicated in the regulation of calcium fluxes. Instead, we found that NS5A contributes to ROS production by activating expression of NADPH oxidases 1 and 4 as well as cytochrome P450 2E1. These effects were mediated by domain I of NS5A protein. NOX1 and NOX4 induction was mediated by enhanced production of transforming growth factor β1 (TGFβ1). Thus, our data show that NS5A protein induces oxidative stress by several multistep mechanisms. Olga A. Smirnova, Olga N. Ivanova, Birke Bartosch, Vladimir T. Valuev-Elliston, Furkat Mukhtarov, Sergey N. Kochetkov, and Alexander V. Ivanov Copyright © 2016 Olga A. Smirnova et al. All rights reserved. The C-ETS2-TFEB Axis Promotes Neuron Survival under Oxidative Stress by Regulating Lysosome Activity Tue, 19 Apr 2016 10:47:31 +0000 http://www.hindawi.com/journals/omcl/2016/4693703/ Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) produced as a result of ageing causes damage to macromolecules and organelles or leads to interference of cell signalling pathways, which in turn results in oxidative stress. Oxidative stress occurs in many neurodegenerative diseases (e.g., Parkinson’s disease) and contributes to progressive neuronal loss. In this study, we show that cell apoptosis is induced by oxidative stress and that lysosomes play an important role in cell survival under oxidative stress. As a compensatory response to this stress, lysosomal genes were upregulated via induction of transcription factor EB (TFEB). In addition, localization of TFEB to the nucleus was increased by oxidative stress. We also confirmed that TFEB protects cells from oxidative stress both in vitro and in vivo. Finally, we found that C-ETS2 senses oxidative stress, activates TFEB transcription, and mediates the upregulation of lysosomal genes. Our results demonstrate a mechanistic pathway for inducing lysosomal activity during ageing and neurodegeneration. Shumin Ma, Zijun Fang, Wenwen Luo, Yunzhi Yang, Chenyao Wang, Qian Zhang, Huafei Wang, Huaiyong Chen, Chi bun Chan, and Zhixue Liu Copyright © 2016 Shumin Ma et al. All rights reserved. Effects of Moderate Aerobic Exercise on Cognitive Abilities and Redox State Biomarkers in Older Adults Mon, 18 Apr 2016 14:17:48 +0000 http://www.hindawi.com/journals/omcl/2016/2545168/ We used a moderate aerobic exercise program for 24 weeks to measure the positive impact of physical activity on oxidative stress and inflammatory markers and its association with cognitive performance in healthy older adults. A total of 100 healthy subjects (65–95 Yrs) were randomly classified into two groups: control group () and exercise group (). Cognitive functioning, physical activity score, MDA, 8-OHdG, TAC, and hs-CRP were assessed using LOTCA battery, prevalidated PA questionnaire, and immunoassay techniques. LOTCA 7-set scores of cognitive performance showed a significant correlation with physical activity status and the regulation of both oxidative stress free radicals and inflammatory markers in all older subjects following 24 weeks of moderate exercise. Physically active persons showed a higher cognitive performance along with reduction in the levels of MDA, 8-OHdG, and hs-CRP and increase in TAC activity compared with sedentary participants. Cognitive performance correlated positively with the increase in TAC activity and physical fitness scores and negatively with MDA, 8-OHdG, and hs-CRP, respectively. There was a significant improvement in motor praxis, vasomotor organization, thinking operations, and attention and concentration among older adults. In conclusion, moderate aerobic training for 24 weeks has a positive significant effect in improving cognitive functions via modulating redox and inflammatory status of older adults. Ahmad H. Alghadir, Sami A. Gabr, and Einas S. Al-Eisa Copyright © 2016 Ahmad H. Alghadir et al. All rights reserved. Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo Mon, 18 Apr 2016 14:14:16 +0000 http://www.hindawi.com/journals/omcl/2016/9785890/ Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine. Krzysztof Marycz, Krzysztof A. Tomaszewski, Katarzyna Kornicka, Brandon Michael Henry, Sebastian Wroński, Jacek Tarasiuk, and Monika Maredziak Copyright © 2016 Krzysztof Marycz et al. All rights reserved. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy Thu, 14 Apr 2016 15:38:59 +0000 http://www.hindawi.com/journals/omcl/2016/1203285/ Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. Xiaochun Duan, Zunjia Wen, Haitao Shen, Meifen Shen, and Gang Chen Copyright © 2016 Xiaochun Duan et al. All rights reserved. Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts Wed, 13 Apr 2016 13:41:28 +0000 http://www.hindawi.com/journals/omcl/2016/8470394/ Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD) and diabetes mellitus (DM). Recently, mitochondrial monoamine oxidases (MAOs) have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs-related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1) Control (CTRL), valvular patients without CHD; (2) CHD, patients with confirmed CHD; and (3) CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2) emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM. O. M. Duicu, R. Lighezan, A. Sturza, R. Balica, A. Vaduva, H. Feier, M. Gaspar, A. Ionac, L. Noveanu, C. Borza, D. M. Muntean, and C. Mornos Copyright © 2016 O. M. Duicu et al. All rights reserved. Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species Wed, 13 Apr 2016 11:46:06 +0000 http://www.hindawi.com/journals/omcl/2016/5057610/ Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS. Jiří Wilhelm, Richard Vytášek, Jiří Uhlík, and Luděk Vajner Copyright © 2016 Jiří Wilhelm et al. All rights reserved. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat Tue, 12 Apr 2016 09:00:06 +0000 http://www.hindawi.com/journals/omcl/2016/5818479/ This study was aimed at evaluating the protective effect of coenzyme Q10 on L-arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1β, and TNF-α, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-α and IL-1β cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role. Seyed Abbas Mirmalek, Ala Gholamrezaei Boushehrinejad, Hassan Yavari, Bahareh Kardeh, Yekta Parsa, Seyed Alireza Salimi-Tabatabaee, Soheila Yadollah-Damavandi, Tina Parsa, Ehsan Shahverdi, and Ehsan Jangholi Copyright © 2016 Seyed Abbas Mirmalek et al. All rights reserved. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat Mon, 11 Apr 2016 14:10:43 +0000 http://www.hindawi.com/journals/omcl/2016/9814038/ Activation of nuclear factor-κB (NF-κB) by increased production of reactive oxygen species (ROS) might induce transcription and expression of different antioxidant enzymes and also of nitric oxide synthase (NOS) isoforms. Thus, we aimed at studying the effect of NF-κB inhibition, caused by JSH-23 (4-methyl--(3-phenyl-propyl)-benzene-1,2-diamine) injection, on ROS and NO generation in hereditary hypertriglyceridemic (HTG) rats. 12-week-old, male Wistar and HTG rats were treated with JSH-23 (bolus, 10 μmol, i.v.). After one week, blood pressure (BP), superoxide dismutase (SOD) activity, SOD1, endothelial NOS (eNOS), and NF-κB (p65) protein expressions were higher in the heart of HTG rats compared to control rats. On the other hand, NOS activity was decreased. In HTG rats, JSH-23 treatment increased BP and heart conjugated dienes (CD) concentration (measured as the marker of tissue oxidative damage). Concomitantly, SOD activity together with SOD1 expression was decreased, while NOS activity and eNOS protein expression were increased significantly. In conclusion, NF-κB inhibition in HTG rats led to decreased ROS degradation by SOD followed by increased oxidative damage in the heart and BP elevation. In these conditions, increased NO generation may represent rather a counterregulatory mechanism activated by ROS. Nevertheless, this mechanism was not sufficient enough to compensate BP increase in HTG rats. Stanislava Vranková, Andrej Barta, Jana Klimentová, Ima Dovinová, Silvia Líšková, Zdenka Dobešová, Oľga Pecháňová, Jaroslav Kuneš, and Josef Zicha Copyright © 2016 Stanislava Vranková et al. All rights reserved. Hydrogen Sulfide: Biogenesis, Physiology, and Pathology Mon, 11 Apr 2016 09:29:05 +0000 http://www.hindawi.com/journals/omcl/2016/6549625/ Jin-Song Bian, Kenneth R. Olson, and Yi-Chun Zhu Copyright © 2016 Jin-Song Bian et al. All rights reserved. Widening and Elaboration of Consecutive Research into Therapeutic Antioxidant Enzyme Derivatives Mon, 11 Apr 2016 08:00:41 +0000 http://www.hindawi.com/journals/omcl/2016/3075695/ Undiminishing actuality of enzyme modification for therapeutic purposes has been confirmed by application of modified enzymes in clinical practice and numerous research data on them. Intravenous injection of the superoxide dismutase-chondroitin sulfate-catalase (SOD-CHS-CAT) conjugate in preventive and medicative regimes in rats with endotoxin shock induced with a lipopolysaccharide bolus has demonstrated that antioxidant agents not only effectively prevent damage caused by oxidative stress (as believed previously) but also can be used for antioxidative stress therapy. The results obtained emphasize the importance of investigation into the pathogenesis of vascular damage and the role of oxidative stress in it. The effects of intravenous medicative injection of SOD-CHS-CAT in a rat model of endotoxin shock have demonstrated a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with superoxide radical. Together with the literature data, these findings offer a prospect for the study of NO-independent therapeutic effects of SOD-CHS-CAT, implying the importance of a better insight into the mechanisms of the conjugate activity in modeled cardiovascular damage involving vasoactive agents other than NO. Alexander V. Maksimenko Copyright © 2016 Alexander V. Maksimenko. All rights reserved. Role of Vanadium in Cellular and Molecular Immunology: Association with Immune-Related Inflammation and Pharmacotoxicology Mechanisms Mon, 11 Apr 2016 06:55:19 +0000 http://www.hindawi.com/journals/omcl/2016/4013639/ Over the last decade, a diverse spectrum of vanadium compounds has arisen as anti-inflammatory therapeutic metallodrugs targeting various diseases. Recent studies have demonstrated that select well-defined vanadium species are involved in many immune-driven molecular mechanisms that regulate and influence immune responses. In addition, advances in cell immunotherapy have relied on the use of metallodrugs to create a “safe,” highly regulated, environment for optimal control of immune response. Emerging findings include optimal regulation of B/T cell signaling and expression of immune suppressive or anti-inflammatory cytokines, critical for immune cell effector functions. Furthermore, in-depth perusals have explored NF-κB and Toll-like receptor signaling mechanisms in order to enhance adaptive immune responses and promote recruitment or conversion of inflammatory cells to immunodeficient tissues. Consequently, well-defined vanadium metallodrugs, poised to access and resensitize the immune microenvironment, interact with various biomolecular targets, such as B cells, T cells, interleukin markers, and transcription factors, thereby influencing and affecting immune signaling. A synthetically formulated and structure-based (bio)chemical reactivity account of vanadoforms emerges as a plausible strategy for designing drugs characterized by selectivity and specificity, with respect to the cellular molecular targets intimately linked to immune responses, thereby giving rise to a challenging field linked to the development of immune system vanadodrugs. Olga Tsave, Savvas Petanidis, Efrosini Kioseoglou, Maria P. Yavropoulou, John G. Yovos, Doxakis Anestakis, Androniki Tsepa, and Athanasios Salifoglou Copyright © 2016 Olga Tsave et al. All rights reserved. Medicinal Plants in Therapy: Antioxidant Activities Mon, 11 Apr 2016 05:57:55 +0000 http://www.hindawi.com/journals/omcl/2016/7468524/ Mohamed A. Dkhil, Denis Delic, Hesham A. El Enshasy, and Ahmed E. Abdel Moneim Copyright © 2016 Mohamed A. Dkhil et al. All rights reserved. Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress Sun, 10 Apr 2016 11:07:10 +0000 http://www.hindawi.com/journals/omcl/2016/7960386/ Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system. Mayra Domínguez-Pérez, Natalia Nuño-Lámbarri, Denise Clavijo-Cornejo, Armando Luna-López, Verónica Souza, Leticia Bucio, Roxana U. Miranda, Linda Muñoz, Luis Enrique Gomez-Quiroz, Salvador Uribe-Carvajal, and María Concepción Gutiérrez-Ruiz Copyright © 2016 Mayra Domínguez-Pérez et al. All rights reserved. Induction Effect of Bisphenol A on Gene Expression Involving Hepatic Oxidative Stress in Rat Sun, 10 Apr 2016 09:45:10 +0000 http://www.hindawi.com/journals/omcl/2016/6298515/ Background and Objective. Bisphenol A (BPA) is an abundantly used xenoestrogenic chemical which may cause various disorders in body. In the present study, we sought to investigate the effects of various doses of BPA on hepatic oxidative stress-related gene expression in rats. Methods. Male Wistar rats weighing 150–200 g were used in this study. Three doses of the BPA (5, 25, and 125 μg/kg) in corn oil were administered as gavage during 35 consecutive days. After the experiment, the rats were expired and the livers were removed and stored at −80°C freezer for RNA extraction. Findings. The Real Time PCR showed increased expression of HO-1 in the rats receiving BPA doses compared to the control group. This effect was dose-dependent and higher at doses of 25 and 125 μg/kg than 5 μg/kg of body weight (). It was also demonstrated that various doses BPA can increase GADD45B gene expression compared to control group. That expression was significantly dominant in the lowest dose (5 μg/kg) of the BPA (). The final body weights ( gr) in the treatment group [BPA (125 μg/kg)] showed a significant decrease compared to control group ( gr). Conclusion. These findings demonstrate that BPA generated ROS and increased the antioxidant gene expression that causes hepatotoxicity. Sohrab Kazemi, Seydeh Narges Mousavi, Fahimeh Aghapour, Boshra Rezaee, Farzin Sadeghi, and Ali Akbar Moghadamnia Copyright © 2016 Sohrab Kazemi et al. All rights reserved. Attenuated Oxidative Stress following Acute Exhaustive Swimming Exercise Was Accompanied with Modified Gene Expression Profiles of Apoptosis in the Skeletal Muscle of Mice Sun, 10 Apr 2016 07:26:37 +0000 http://www.hindawi.com/journals/omcl/2016/8381242/ Purpose. The purpose of the present study was to investigate the effect of acute exhaustive swimming exercise on apoptosis in the skeletal muscle of mice. Method. C57BL/6 mice were averagely divided into seven groups. One group was used as control (C), while the remaining six groups went through one-time exhaustive swimming exercise and were terminated at 0 h, 2 h, 6 h, 12 h, 24 h, and 48 h upon completion of exercise. Result. ABTS was significantly lowered at 12 h and 48 h after exercise. The MDA level was significantly decreased at any time points sampled following exercise. Total SOD activity was significantly decreased at 6 h, 12 h, 24 h, and 48 h after exercise. Neither mRNA of Bax nor Bax/Bcl-2 ratio was significantly altered by exercise. mRNA of Bcl-2 was significantly decreased since 6 h after exercise. mRNA and protein expressions of PGC-1α were significantly increased at different time points following exercise. Conclusion. Cellular oxidative stress level was decreased following low intensity, long duration acute exhaustive swimming exercise in mice, and the enzymatic antioxidant capacity was compromised. Apoptosis of the skeletal muscle was inhibited, which could partially be explained by the enhanced level of PGC-1α. Yi Sun, Di Cui, Zhe Zhang, Tan Zhang, Jun Shi, Haixiu Jin, Zhe Ge, Liu Ji, and Shuzhe Ding Copyright © 2016 Yi Sun et al. All rights reserved. Lycium barbarum Polysaccharides Protect against Trimethyltin Chloride-Induced Apoptosis via Sonic Hedgehog and PI3K/Akt Signaling Pathways in Mouse Neuro-2a Cells Thu, 07 Apr 2016 13:36:43 +0000 http://www.hindawi.com/journals/omcl/2016/9826726/ Trimethyltin chloride (TMT) is a classic neurotoxicant that can cause severe neurodegenerative diseases. Some signaling pathways involving cell death play pivotal roles in the central nervous system. In this study, the role of Sonic Hedgehog (Shh) and PI3K/Akt pathways in TMT-induced apoptosis and protective effect of Lycium barbarum polysaccharides (LBP) on mouse neuro-2a (N2a) cells were investigated. Results showed that TMT treatment significantly enhanced apoptosis, upregulated proapoptotic Bax, downregulated antiapoptotic Bcl-2 expression, and increased caspase-3 activity in a dose-dependent manner in N2a cells. TMT induced oxidative stress in cells, performing reactive oxygen species (ROS) and malondialdehyde (MDA) excessive generation, and superoxide dismutase (SOD) activity reduction. TMT significantly decreased phosphorylated glycogen synthase kinase-3β (GSK-3β) and inhibited Shh and PI3K/Akt pathways. However, the addition of LBP upregulated GSK-3β phosphorylation, activated Shh and PI3K/Akt pathways, and eventually reduced apoptosis and oxidative stress caused by TMT. The interaction between Shh and PI3K/Akt pathways was clarified by specific PI3K inhibitor LY294002 or Shh inhibitor GDC-0449. Moreover, LY294002 and GDC-0449 pretreatment both induced phosphorylated GSK-3β downregulation and significantly promoted apoptosis induced by TMT. These results suggest that LBP could reduce TMT-induced N2a cells apoptosis by regulating GSK-3β phosphorylation, Shh, and PI3K/Akt signaling pathways. Wanyun Zhao, Xiaoqi Pan, Tao Li, Changchun Zhang, and Nian Shi Copyright © 2016 Wanyun Zhao et al. All rights reserved. The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases Wed, 06 Apr 2016 11:30:20 +0000 http://www.hindawi.com/journals/omcl/2016/2795090/ High heterogeneity of macrophage is associated with its functions in polarization to different functional phenotypes depending on environmental cues. Macrophages remain in balanced state in healthy subject and thus macrophage polarization may be crucial in determining the tissue fate. The two distinct populations, classically M1 and alternatively M2 activated, representing the opposing ends of the full activation spectrum, have been extensively studied for their associations with several disease progressions. Accumulating evidences have postulated that the redox signalling has implication in macrophage polarization and the key roles of M1 and M2 macrophages in tissue environment have provided the clue for the reasons of ROS abundance in certain phenotype. M1 macrophages majorly clearing the pathogens and ROS may be crucial for the regulation of M1 phenotype, whereas M2 macrophages resolve inflammation which favours oxidative metabolism. Therefore how ROS play its role in maintaining the homeostatic functions of macrophage and in particular macrophage polarization will be reviewed here. We also review the biology of macrophage polarization and the disturbance of M1/M2 balance in human diseases. The potential therapeutic opportunities targeting ROS will also be discussed, hoping to provide insights for development of target-specific delivery system or immunomodulatory antioxidant for the treatment of ROS-related diseases. Hor-Yue Tan, Ning Wang, Sha Li, Ming Hong, Xuanbin Wang, and Yibin Feng Copyright © 2016 Hor-Yue Tan et al. All rights reserved. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy Wed, 06 Apr 2016 09:56:52 +0000 http://www.hindawi.com/journals/omcl/2016/3528274/ Oxidative stress and inflammation are important pathogenic factors contributing to the etiology of diabetic retinopathy (DR). Melatonin is an endogenous hormone that exhibits a variety of biological effects including antioxidant and anti-inflammatory functions. The goals of this study were to determine whether melatonin could ameliorate retinal injury and to explore the potential mechanisms. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Melatonin (10 mg kg−1 daily, i.p.) was administered from the induction of diabetes and continued for up to 12 weeks, after which the animals were sacrificed and retinal samples were collected. The retina of diabetic rats showed depletion of glutathione and downregulation of glutamate cysteine ligase (GCL). Melatonin significantly upregulated GCL by retaining Nrf2 in the nucleus and stimulating Akt phosphorylation. The production of proinflammatory cytokines and proteins, including interleukin 1β, TNF-α, and inducible nitric oxide synthase (iNOS), was inhibited by melatonin through the NF-κB pathway. At 12 weeks, melatonin prevented the significant decrease in the ERG a- and b-wave amplitudes under the diabetic condition. Our results suggest potent protective functions of melatonin in diabetic retinopathy. In addition to being a direct antioxidant, melatonin can exert receptor-mediated signaling effects to attenuate inflammation and oxidative stress of the retina. Tingting Jiang, Qing Chang, Jiyang Cai, Jiawen Fan, Xiaozhe Zhang, and Gezhi Xu Copyright © 2016 Tingting Jiang et al. All rights reserved. Phytochemical Composition, Antifungal and Antioxidant Activity of Duguetia furfuracea A. St.-Hill Tue, 05 Apr 2016 08:57:44 +0000 http://www.hindawi.com/journals/omcl/2016/7821051/ Background. Duguetia furfuracea is popular plant used in popular medicine. Hypothesis/Purpose. This claim evaluated the phytochemical composition of the hydroethanolic extract (HEDF), fractions of Duguetia furfuracea, and antioxidant and antifungal activity. Methods. The chemical profile was carried out by HPLC-DAD. The total phenolic contents and flavonoid components were determined by Folin-Ciocalteu and aluminium chloride reaction. The antioxidant activity was measured by scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and ferric reducing ability of plasma (FRAP) methods. The antifungal activity was determined by microdilution assay. Results. HPLC analysis revealed caffeic acid and rutin as major compounds (HEDF), caffeic acid and quercitrin (Mt-OH fraction), and quercitrin and isoquercitrin (Ac-OEt fraction). The highest levels of phenols and total flavonoids were found for Ac-OEt fraction, and the crude extract showed higher in vitro antioxidant potential. The antifungal activity showed synergic effect with fluconazole and EHDF against C. krusei, fluconazole and Mt-OH against C. krusei and C. tropicalis, and Ac-OE and fluconazole against C. albicans. Conclusion. The highest levels of phenols and total flavonoids were marked with antioxidant effect. This is the first report of bioactivity of the synergic effect of HEDF and fractions. More studies would be required to better clarify its mechanism of synergic action. Francisca Valéria Soares de Araújo Pinho, Litiele Cezar da Cruz, Nathane Rosa Rodrigues, Emily Pansera Waczuk, Celestina Elba Sobral Souza, Henrique Douglas Melo Coutinho, José Galberto Martins da Costa, Margareth Linde Athayde, Aline Augusti Boligon, Jeferson Luis Franco, Thaís Posser, and Irwin Rose Alencar de Menezes Copyright © 2016 Francisca Valéria Soares de Araújo Pinho et al. All rights reserved.