Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Vanadium Toxicological Potential versus Its Pharmacological Activity: New Developments and Research Mon, 29 Aug 2016 12:34:41 +0000 http://www.hindawi.com/journals/omcl/2016/7612347/ Agnieszka Ścibior, Juan Llopis, Alvin A. Holder, and Mario Altamirano-Lozano Copyright © 2016 Agnieszka Ścibior et al. All rights reserved. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases Mon, 29 Aug 2016 08:53:25 +0000 http://www.hindawi.com/journals/omcl/2016/7364138/ Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases. Maurizio Forte, Valeria Conti, Antonio Damato, Mariateresa Ambrosio, Annibale A. Puca, Sebastiano Sciarretta, Giacomo Frati, Carmine Vecchione, and Albino Carrizzo Copyright © 2016 Maurizio Forte et al. All rights reserved. Alterations in Red Blood Cell Functionality Induced by an Indole Scaffold Containing a Y-Iminodiketo Moiety: Potential Antiproliferative Conditions Mon, 29 Aug 2016 06:27:35 +0000 http://www.hindawi.com/journals/omcl/2016/2104247/ We have recently proposed a new erythrocyte-based model of study to predict the antiproliferative effects of selected heterocyclic scaffolds. Starting from the metabolic similarity between erythrocytes and cancer cells, we have demonstrated how the metabolic derangement induced by an indolone-based compound (DPIT) could be related to its antiproliferative effects. In order to prove the validity of our biochemical approach, in the present study the effects on erythrocyte functionality of its chemical precursor (PID), whose synthesis we reported, were investigated. The influence of the tested compound on band 3 protein (B3), oxidative state, ATP efflux, caspase 3, metabolism, intracellular pH, and Ca2+ homeostasis has been evaluated. PID crosses the membrane localizing into the cytosol, increases anion exchange, induces direct caspase activation, shifts the erythrocytes towards an oxidative state, and releases less ATP than in normal conditions. Analysis of phosphatidylserine externalization shows that PID slightly induces apoptosis. Our findings indicate that, due to its unique features, erythrocyte responses to exogenous molecular stimuli can be fruitfully correlated at structurally more complex cells, such as cancer cells. Overall, our work indicates that erythrocyte is a powerful study tool to elucidate the biochemical/biological effects of selected heterocycles opening considerable perspectives in the field of drug discovery. Angela Scala, Silvana Ficarra, Annamaria Russo, Davide Barreca, Elena Giunta, Antonio Galtieri, Giovanni Grassi, and Ester Tellone Copyright © 2016 Angela Scala et al. All rights reserved. Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation Sun, 28 Aug 2016 16:50:02 +0000 http://www.hindawi.com/journals/omcl/2016/7894247/ Fibroblasts are essential for tissue repair due to producing collagens, and lysosomal proteinase cathepsin B (CatB) is involved in promoting chronic inflammation. We herein report that CatB regulates the expression of collagens III and IV by fibroblasts in response to a TLR2 agonist, lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). In cultured human BJ fibroblasts, mRNA expression of CatB was significantly increased, while that of collagens III and IV was significantly decreased at 24 h after challenge with P.g. LPS (1 μg/mL). The P.g. LPS-decreased collagen expression was completely inhibited by CA-074Me, the specific inhibitor of CatB. Surprisingly, expression of collagens III and IV was significantly increased in the primary fibroblasts from CatB-deficient mice after challenge with P.g. LPS. The increase of CatB was accompanied with an increase of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and a decrease of IκBα. Furthermore, the P.g. LPS-increased 8-OHdG and decreased IκBα were restored by CA-074Me. Moreover, 87% of CatB and 86% of 8-OHdG were colocalized with gingival fibroblasts of chronic periodontitis patients. The findings indicate the critical role of CatB in regulating the expression of collagens III and IV by fibroblasts via prolonging TLR2/NF-κB activation and oxidative stress. CatB-specific inhibitors may therefore improve chronic inflammation-delayed tissue repair. Xue Li, Zhou Wu, Junjun Ni, Yicong Liu, Jie Meng, Weixian Yu, Hiroshi Nakanishi, and Yanmin Zhou Copyright © 2016 Xue Li et al. All rights reserved. Differential Regulation of the Extracellular Cysteine/Cystine Redox State (EhCySS) by Lung Fibroblasts from Young and Old Mice Thu, 25 Aug 2016 17:01:27 +0000 http://www.hindawi.com/journals/omcl/2016/1561305/ Aging is associated with progressive oxidation of plasma cysteine (Cys)/cystine (CySS) redox state, expressed as . Cultured cells condition their media to reproduce physiological , but it is unknown whether aged cells produce a more oxidized extracellular environment reflective of that seen in vivo. In the current study, we isolated primary lung fibroblasts from young and old female mice and measured the media before and after challenge with Cys or CySS. We also measured expression of genes related to redox regulation and fibroblast function. These studies revealed that old fibroblasts produced a more oxidizing extracellular than young fibroblasts and that old fibroblasts had a decreased capacity to recover from an oxidative challenge due to a slower rate of reduction of CySS to Cys. These defects were associated with 10-fold lower expression of the Slc7a11 subunit of the xCT cystine-glutamate transporter. Extracellular superoxide dismutase (Sod3) was the only antioxidant or thiol-disulfide regulating enzyme among 36 examined that was downregulated in old fibroblasts by more than 2-fold, but there were numerous changes in extracellular matrix components. Thus, aging fibroblasts not only contribute to remodeling of the extracellular matrix but also have a profound effect on the extracellular redox environment. Walter H. Watson, Tom J. Burke, Igor N. Zelko, Edilson Torres-González, Jeffrey D. Ritzenthaler, and Jesse Roman Copyright © 2016 Walter H. Watson et al. All rights reserved. Açai (Euterpe oleracea Mart.) Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats Thu, 25 Aug 2016 13:07:55 +0000 http://www.hindawi.com/journals/omcl/2016/8379105/ Açai (Euterpe oleracea Mart.), a fruit from the Amazon region, has emerged as a promising source of polyphenols. Açai consumption has been increasing owing to ascribed health benefits and antioxidant properties; however, its effects on hepatic injury are limited. In this study, we evaluated the antioxidant effect of filtered açai pulp on the expression of paraoxonase (PON) isoforms and PON1 activity in rats with nonalcoholic fatty liver disease (NAFLD). The rats were fed a standard AIN-93M (control) diet or a high-fat (HF) diet containing 25% soy oil and 1% cholesterol with or without açai pulp (2 g/day) for 6 weeks. Our results show that açai pulp prevented low-density lipoprotein (LDL) oxidation, increased serum and hepatic PON1 activity, and upregulated the expression of PON1 and ApoA-I in the liver. In HF diet-fed rats, treatment with açai pulp attenuated liver damage, reducing fat infiltration and triglyceride (TG) content. In rats receiving açai, increased serum PON1 activity was correlated with a reduction in hepatic steatosis and hepatic injury. These findings suggest the use of açai as a potential therapy for liver injuries, supporting the idea that dietary antioxidants are a promising approach to enhance the defensive systems against oxidative stress. Renata Rebeca Pereira, Isabel Cristina Mallosto Emerich de Abreu, Joyce Ferreira da Costa Guerra, Nara Nunes Lage, Juliana Márcia Macedo Lopes, Maísa Silva, Wanderson Geraldo de Lima, Marcelo Eustáquio Silva, and Maria Lucia Pedrosa Copyright © 2016 Renata Rebeca Pereira et al. All rights reserved. Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia Thu, 25 Aug 2016 11:13:10 +0000 http://www.hindawi.com/journals/omcl/2016/3406802/ To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples. Testis histopathology was assessed after hematoxylin-eosin staining by Johnsen’s testicular scoring system. Meanwhile, testosterone synthase and vimentin amounts were assessed by immunohistochemistry. Sperm count, motility, and density were assessed to determine epididymal sperm quality. IHH treatment induced significant pathological changes in testicular tissue and enhanced serum lipid peroxide levels, while reducing serum FRAP, antioxidant enzyme activities, and testosterone synthase expression. Moreover, IHH impaired epididymal sperm quality and vimentin structure in Sertoli cells. Oral administration of PTX improved the pathological changes in the testis. IHH may impair spermatogenesis function of testicular tissues by inducing oxidative stress, but this impairment could be attenuated by administration of PTX. Chen Yao, Gang Li, Yeyong Qian, Ming Cai, Hong Yin, Li Xiao, Wei Tang, Fengjie Guo, and Bingyi Shi Copyright © 2016 Chen Yao et al. All rights reserved. Oxidation-Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury Thu, 25 Aug 2016 10:08:14 +0000 http://www.hindawi.com/journals/omcl/2016/6974257/ There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation-reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at . Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients’ response to brain injury over time is a factor that determines outcome. Kimberly B. Bjugstad, Leonard T. Rael, Stewart Levy, Matthew Carrick, Charles W. Mains, Denetta S. Slone, and David Bar-Or Copyright © 2016 Kimberly B. Bjugstad et al. All rights reserved. The Janus-Faced Role of Antioxidants in Cancer Cachexia: New Insights on the Established Concepts Wed, 24 Aug 2016 11:44:24 +0000 http://www.hindawi.com/journals/omcl/2016/9579868/ Chronic inflammation and excessive loss of skeletal muscle usually occur during cancer cachexia, leading to functional impairment and delaying the cure of cancer. The release of cytokines by tumor promotes the formation of reactive oxygen species (ROS), which in turn regulate catabolic pathways involved in muscle atrophy. ROS also exert a dual role within tumor itself, as they can either promote proliferation and vascularization or induce senescence and apoptosis. Accordingly, previous studies that used antioxidants to modulate these ROS-dependent mechanisms, in cancer and cancer cachexia, have obtained contradictory results, hence the need to gather the main findings of these studies and draw global conclusions in order to stimulate more oriented research in this field. Based on the literature reviewed in this paper, it appears that antioxidant supplementation is (1) beneficial in cancer cachectic patients with antioxidant deficiencies, (2) most likely harmful in cancer patients with adequate antioxidant status (i.e., lung, gastrointestinal, head and neck, and esophageal), and (3) not recommended when undergoing radiotherapy. At the moment, measuring the blood levels of antioxidants may help to identify patients with systemic deficiencies. This approach is simple to realize but could not be a gold standard method for cachexia, as it does not necessarily reflect the redox state in other organs, like muscle. Mohamad Assi and Amélie Rébillard Copyright © 2016 Mohamad Assi and Amélie Rébillard. All rights reserved. Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins Tue, 23 Aug 2016 14:04:33 +0000 http://www.hindawi.com/journals/omcl/2016/9340654/ Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS) generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs), specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection. Angélica Ruiz-Ramírez, Ocarol López-Acosta, Miguel Angel Barrios-Maya, and Mohammed El-Hafidi Copyright © 2016 Angélica Ruiz-Ramírez et al. All rights reserved. Hydrogen Sulfide Improves Endothelial Dysfunction via Downregulating BMP4/COX-2 Pathway in Rats with Hypertension Tue, 23 Aug 2016 13:24:15 +0000 http://www.hindawi.com/journals/omcl/2016/8128957/ Aims. We object to elucidate that protective effect of H2S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56 μmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from  mmHg to  mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats. 2K1C reduced CSE level twofold, decreased plasma levels of H2S about 6-fold, increased BMP4, Nox2, and Nox4 levels 2-fold and increased markers of oxidative stress MDA and nitrotyrosine 1.5-fold, upregulated the expression of phosphorylation-p38 MAPK 2-fold, and increased protein levels of COX-2 1.5-fold, which were abolished by NaHS treatment. Conclusions. Our results demonstrate that H2S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H2S on endothelial impairment. These results throw light on endothelial protective effect of H2S and provide new target for prevention and therapy of hypertension. Lin Xiao, Jing-Hui Dong, Sheng Jin, Hong-Mei Xue, Qi Guo, Xu Teng, and Yu-Ming Wu Copyright © 2016 Lin Xiao et al. All rights reserved. AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells Mon, 22 Aug 2016 13:23:21 +0000 http://www.hindawi.com/journals/omcl/2016/1531392/ Recent studies suggest that the epithelial sodium channel (ENaC) is expressed in the endothelial cells. To test whether high salt affects the NO production via regulation of endothelial ENaC, human umbilical vein endothelial cells (HUVECs) were incubated in solutions containing either normal or high sodium (additional 20 mM NaCl). Our data showed that high sodium treatment significantly increased α-, β-, and γ-ENaC expression levels in HUVECs. Using the cell-attached patch-clamp technique, we demonstrated that high sodium treatment significantly increased ENaC open probability (). Moreover, nitric oxide synthase (eNOS) phosphorylation (Ser 1177) levels and NO production were significantly decreased by high sodium in HUVECs; the effects of high sodium on eNOS phosphorylation and NO production were inhibited by a specific ENaC blocker, amiloride. Our results showed that high sodium decreased AMP-activated kinase (AMPK) phosphorylation in endothelial cells. On the other hand, metformin, an AMPK activator, prevented high sodium-induced upregulation of ENaC expression and . Moreover, metformin prevented high salt-induced decrease in NO production and eNOS phosphorylation. These results suggest that high sodium stimulates ENaC activation by negatively modulating AMPK activity, thereby leading to reduction in eNOS activity and NO production in endothelial cells. Wei-Wan Zheng, Xin-Yuan Li, Hui-Bin Liu, Zi-Rui Wang, Qing-Qing Hu, Yu-Xia Li, Bin-Lin Song, Jie Lou, Qiu-Shi Wang, He-Ping Ma, and Zhi-Ren Zhang Copyright © 2016 Wei-Wan Zheng et al. All rights reserved. Functionalized Fullerene Increases NF-κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum-Starving Human Embryo Lung Diploid Fibroblasts Sun, 21 Aug 2016 13:46:48 +0000 http://www.hindawi.com/journals/omcl/2016/9895245/ The influence of a water-soluble [] fullerene derivative containing five residues of 3-phenylpropionic acid and a chlorine addend appended to the carbon cage (F-828) on serum-starving human embryo lung diploid fibroblasts (HELFs) was studied. Serum deprivation evokes oxidative stress in HELFs. Cultivation of serum-starving HELFs in the presence of 0.1–1 µM F-828 significantly decreases the level of free radicals, inhibits autophagy, and represses expression of NOX4 and NRF2 proteins. The activity of NF-κB substantially grows up in contrast to the suppressed NRF2 activity. In the presence of 0.2–0.25 µM F-828, the DSB rate and apoptosis level dramatically decrease. The maximum increase of proliferative activity of the HELFs and maximum activity of NF-κB are observed at these concentration values. Conclusion. Under the conditions of oxidative stress evoked by serum deprivation the water-soluble fullerene derivative F-828 used in concentrations of 0.1 to 1 µM strongly stimulates the NF-κB activity and represses the NRF2 activity in HELFs. E. S. Ershova, V. A. Sergeeva, V. J. Tabakov, L. A. Kameneva, L. N. Porokhovnik, I. I. Voronov, E. A. Khakina, P. A. Troshin, S. I. Kutsev, N. N. Veiko, and S. V. Kostyuk Copyright © 2016 E. S. Ershova et al. All rights reserved. A Case-Control Study on the Oxidative Balance of 50% Autologous Serum Eye Drops Sun, 21 Aug 2016 12:11:22 +0000 http://www.hindawi.com/journals/omcl/2016/9780193/ Importance. Autologous serum (AS) eye drops are recommended for severe dry eye in patients with ocular surface disease. No description of the antioxidant balance of AS eye drops has been reported in the literature. Objective. This study sought to evaluate the total reactive antioxidant potential (TRAP) and concentration of reactive oxygen species (ROS) in samples of 50% AS eye drops and their correlations with the demographic characteristics and lifestyle habits of patients with ocular surface disease and healthy controls. Design. This was a case-control study with a 3-month follow-up period. Participants. 16 patients with severe dry eye disease of different etiologies and 17 healthy controls matched by age, gender, and race were included. Results. TRAP and ROS were detected at all evaluated times. There were no differences in the mean ROS () or TRAP () levels between cases and controls. No statistically significant differences in the concentrations of ROS or TRAPs were found at 0, 15, or 30 days ( for ROS = 0.087 and for TRAP = 0.93). Neither the demographic characteristics nor the lifestyle habits were correlated with the oxidative balance of the 50% AS eye drops. Conclusions and Relevance. Both fresh and frozen 50% AS eye drops present antioxidant capacities and ROS in an apparently stable balance. Moreover, patients with ocular surface disease and normal controls produce equivalent AS eye drops in terms of oxidative properties. Patrícia Ioschpe Gus, Diane Marinho, Samira Zelanis, Adriane Belló-Klein, Claudete Locatelli, Felipe Nicola, Ana Laura Kunzler, Tania Regina Gatelli Fernandes, Cristina Campos Carraro, and Luciene Barbosa Copyright © 2016 Patrícia Ioschpe Gus et al. All rights reserved. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice Sun, 21 Aug 2016 06:21:55 +0000 http://www.hindawi.com/journals/omcl/2016/9895176/ Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress. Natalia Nuño-Lámbarri, Mayra Domínguez-Pérez, Anna Baulies-Domenech, Maria J. Monte, Jose J. G. Marin, Patricia Rosales-Cruz, Verónica Souza, Roxana U. Miranda, Leticia Bucio, Eduardo E. Montalvo-Jave, María Concepción Gutiérrez-Ruiz, Carmen García-Ruiz, José C. Fernández-Checa, and Luis Enrique Gomez-Quiroz Copyright © 2016 Natalia Nuño-Lámbarri et al. All rights reserved. In Vitro Evaluation of the Antioxidant Activity and Wound Healing Properties of Jaboticaba (Plinia peruviana) Fruit Peel Hydroalcoholic Extract Thu, 18 Aug 2016 13:45:49 +0000 http://www.hindawi.com/journals/omcl/2016/3403586/ Jaboticaba is a fruit from a native tree to Brazil, Plinia peruviana. Jaboticaba peels are an important source of antioxidant molecules such as phenolic compounds. This study aimed to evaluate in vitro the activity of a hydroalcoholic extract of jaboticaba fruit peels (HEJFP) in wound healing processes and antioxidant activity in murine fibroblasts (L929 cell line). HEJFP concentrations (0.5, 1, 5, 10, 25, 50, 100, and 200 µg/mL) were tested in MTT assay and cell proliferation was verified at 100 µg/mL after 24 h and at 25, 50, and 100 µg/mL after 48 h of extract exposure. Evaluation of antioxidant activity was performed at 0.5, 5, 25, 50, and 100 µg/mL HEJFP concentrations. Cell treatment with HEJFP at 25, 50, and 100 µg/mL for 24 h followed by H2O2 exposure for 3 h showed a strong cytoprotective effect. In vitro scratch wound healing assay indicated that none of tested HEJFP concentrations (0.5, 5, 25, 50, and 100 µg/mL) were capable of increasing migration rate after 12 h of incubation. These results demonstrate a positive effect of HEJFP on the wound healing process on L929 fibroblasts cell line, probably due to the antioxidant activity exhibited by phytochemicals in the extract. Heloisa da S. Pitz, Aline Pereira, Mayara B. Blasius, Ana Paula L. Voytena, Regina C. L. Affonso, Simone Fanan, Adriana C. D. Trevisan, Rosa M. Ribeiro-do-Valle, and Marcelo Maraschin Copyright © 2016 Heloisa da S. Pitz et al. All rights reserved. Effect of Cross-Sex Hormonal Replacement on Antioxidant Enzymes in Rat Retroperitoneal Fat Adipocytes Thu, 18 Aug 2016 13:44:48 +0000 http://www.hindawi.com/journals/omcl/2016/1527873/ We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2 exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2 deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes. Israel Pérez-Torres, Verónica Guarner-Lans, Alejandra Zúñiga-Muñoz, Rodrigo Velázquez Espejel, Alfredo Cabrera-Orefice, Salvador Uribe-Carvajal, and Natalia Pavón Copyright © 2016 Israel Pérez-Torres et al. All rights reserved. Lower Superoxide Dismutase 2 (SOD2) Protein Content in Mononuclear Cells Is Associated with Better Survival in Patients with Hemodialysis Therapy Thu, 18 Aug 2016 12:31:51 +0000 http://www.hindawi.com/journals/omcl/2016/7423249/ Mitochondrial superoxide dismutase 2 (SOD2) converts superoxide anions to hydrogen peroxide and oxygen. Human data on SOD2 protein content in chronic kidney disease (CKD) are sparse and mortality data are lacking. We investigated SOD2 protein content in monocytes from patients with hemodialysis therapy (), CKD stage 1–5 (), and healthy controls () using in-cell Western assays. SOD2 protein decreased from CKD stage 1 until stage 4 whereas it increased again in stage 5 with and without hemodialysis. SOD2 gene expression, analyzed by quantitative real-time PCR, was not significantly different between the groups. Elevating cellular superoxide production reduced SOD2 protein content. This effect was abolished by the superoxide dismutase mimetic Tempol. Using gelelectrophoresis and Western blot we did not detect nitrotyrosine modifications of SOD2 in CKD. Finally, in patients with CKD stage 5 with hemodialysis therapy higher than median SOD2 protein content was associated with higher all-cause mortality. In conclusion, SOD2 protein content declined in CKD until stage 4 while SOD2 gene expression did not. Increased cellular superoxide anion production might affect SOD2 protein content. In advanced CKD (stage 5) SOD2 protein content increased again, but higher than median SOD2 protein content in these patients did not confer a survival benefit. Katharina Krueger, Jianlin Shen, Alexandra Maier, Martin Tepel, and Alexandra Scholze Copyright © 2016 Katharina Krueger et al. All rights reserved. Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters Thu, 18 Aug 2016 11:34:23 +0000 http://www.hindawi.com/journals/omcl/2016/9057593/ Sarcopenia is the loss of muscle mass accompanied by a decrease in muscle strength and resistance and is the main cause of disability among the elderly. Muscle loss begins long before there is any clear physical impact in the senior adult. Despite all this, the molecular mechanisms underlying muscle aging are far from being understood. Recent studies have identified that not only mitochondrial metabolic dysfunction but also mitochondrial dynamics and mitochondrial calcium uptake could be involved in the degeneration of skeletal muscle mass. Mitochondrial homeostasis influences muscle quality which, in turn, could play a triggering role in signaling of systemic aging. Thus, it has become apparent that mitochondrial status in muscle cells could be a driver of whole body physiology and organismal aging. In the present review, we discuss the existing evidence for the mitochondria related mechanisms underlying the appearance of muscle aging and sarcopenia in flies and mice. Andrea del Campo, Enrique Jaimovich, and Maria Florencia Tevy Copyright © 2016 Andrea del Campo et al. All rights reserved. Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy Thu, 18 Aug 2016 09:30:38 +0000 http://www.hindawi.com/journals/omcl/2016/3030547/ Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD. Antonina Luca, Carmela Calandra, and Maria Luca Copyright © 2016 Antonina Luca et al. All rights reserved. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity Wed, 17 Aug 2016 10:00:54 +0000 http://www.hindawi.com/journals/omcl/2016/5152029/ Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function. Elena Barbieri, Michele Guescini, Cinzia Calcabrini, Luciana Vallorani, Anna Rita Diaz, Carmela Fimognari, Barbara Canonico, Francesca Luchetti, Stefano Papa, Michela Battistelli, Elisabetta Falcieri, Vanina Romanello, Marco Sandri, Vilberto Stocchi, Caterina Ciacci, and Piero Sestili Copyright © 2016 Elena Barbieri et al. All rights reserved. Identification of MicroRNAs Involved in Growth Arrest and Apoptosis in Hydrogen Peroxide-Treated Human Hepatocellular Carcinoma Cell Line HepG2 Mon, 15 Aug 2016 06:39:54 +0000 http://www.hindawi.com/journals/omcl/2016/7530853/ Although both oxidative stress and microRNAs (miRNAs) play vital roles in physiological and pathological processes, little is known about the interactions between them. In this study, we first described the regulation of H2O2 in cell viability, proliferation, cycle, and apoptosis of human hepatocellular carcinoma cell line HepG2. Then, miRNAs expression was profiled after H2O2 treatment. The results showed that high concentration of H2O2 (600 μM) could decrease cell viability, inhibit cell proliferation, induce cell cycle arrest, and finally promote cell apoptosis. Conversely, no significant effects could be found under treatment with low concentration (30 μM). miRNAs array analysis identified 131 differentially expressed miRNAs (125 were upregulated and 6 were downregulated) and predicted 13504 putative target genes of the deregulated miRNAs. Gene ontology (GO) analysis revealed that the putative target genes were associated with H2O2-induced cell growth arrest and apoptosis. The subsequent bioinformatics analysis indicated that H2O2-response pathways, including MAPK signaling pathway, apoptosis, and pathways in cancer and cell cycle, were significantly affected. Overall, these results provided comprehensive information on the biological function of H2O2 treatment in HepG2 cells. The identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for liver cancer. Yuan Luo, Xinyu Wen, Ling Wang, Jing Gao, Zi Wang, Chunyan Zhang, Pengjun Zhang, Chengrong Lu, Lianning Duan, and Yaping Tian Copyright © 2016 Yuan Luo et al. All rights reserved. Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update Mon, 15 Aug 2016 06:17:17 +0000 http://www.hindawi.com/journals/omcl/2016/7813072/ Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies. Cheng Wan, Hua Su, and Chun Zhang Copyright © 2016 Cheng Wan et al. All rights reserved. Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation Sun, 14 Aug 2016 08:02:43 +0000 http://www.hindawi.com/journals/omcl/2016/8474303/ Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders. Jiayu Tang, Zhiping Hu, Jieqiong Tan, Sonlin Yang, and Liuwang Zeng Copyright © 2016 Jiayu Tang et al. All rights reserved. Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus Thu, 11 Aug 2016 16:18:36 +0000 http://www.hindawi.com/journals/omcl/2016/2526174/ Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. The pathogenic mechanisms that cause SLE remain unclear; however, it is well recognized that the immune balance is disturbed and that this imbalance contributes to the autoimmune symptoms of SLE. Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and the ability of the biological system to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is involved in many diseases, including atherosclerosis, myocardial infarction, and autoimmune diseases. Numerous studies have confirmed that oxidative stress plays an important role in the pathogenesis of SLE. This review mainly focuses on the recent research advances with respect to oxidative stress and regulatory T (Treg)/helper T 17 (Th17) cell dysfunction in the pathogenesis of SLE. Ji Yang, Xue Yang, Hejian Zou, and Ming Li Copyright © 2016 Ji Yang et al. All rights reserved. Hydrogen Sulfide Alleviates Postharvest Senescence of Grape by Modulating the Antioxidant Defenses Wed, 10 Aug 2016 07:28:18 +0000 http://www.hindawi.com/journals/omcl/2016/4715651/ Hydrogen sulfide (H2S) has been identified as an important gaseous signal in plants. Here, we investigated the mechanism of H2S in alleviating postharvest senescence and rotting of Kyoho grape. Exogenous application of H2S released from 1.0 mM NaHS remarkably decreased the rotting and threshing rate of grape berries. H2S application also prevented the weight loss in grape clusters and inhibited the decreases in firmness, soluble solids, and titratable acidity in grape pulp during postharvest storage. The data of chlorophyll and carotenoid content suggested the role of H2S in preventing chlorophyll breakdown and carotenoid accumulation in both grape rachis and pulp. In comparison to water control, exogenous H2S application maintained significantly higher levels of ascorbic acid and flavonoid and total phenolics and reducing sugar and soluble protein in grape pulp. Meanwhile, H2S significantly reduced the accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion () in grape pulp. Further investigations showed that H2S enhanced the activities of antioxidant enzymes ascorbate peroxidase (APX) and catalase (CAT) and decreased those of lipoxygenase (LOX) in both grape peels and pulp. In all, we provided strong evidence that H2S effectively alleviated postharvest senescence and rotting of Kyoho grape by modulating antioxidant enzymes and attenuating lipid peroxidation. Zhi-Jing Ni, Kang-Di Hu, Chang-Bing Song, Run-Hui Ma, Zhi-Rong Li, Ji-Lian Zheng, Liu-Hui Fu, Zhao-Jun Wei, and Hua Zhang Copyright © 2016 Zhi-Jing Ni et al. All rights reserved. Mitochondrial Dysfunction Contributes to Hypertensive Target Organ Damage: Lessons from an Animal Model of Human Disease Tue, 09 Aug 2016 15:37:31 +0000 http://www.hindawi.com/journals/omcl/2016/1067801/ Mechanisms underlying hypertensive target organ damage (TOD) are not completely understood. The pathophysiological role of mitochondrial oxidative stress, resulting from mitochondrial dysfunction, in development of TOD is unclear. The stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable model of human hypertension and of its vascular consequences. Pathogenesis of TOD in SHRSP is multifactorial, being determined by high blood pressure levels, high salt/low potassium diet, and genetic factors. Accumulating evidence points to a key role of mitochondrial dysfunction in increased susceptibility to TOD development of SHRSP. Mitochondrial abnormalities were described in both heart and brain of SHRSP. Pharmacological compounds able to protect mitochondrial function exerted a significant protective effect on TOD development, independently of blood pressure levels. Through our research efforts, we discovered that two genes encoding mitochondrial proteins, one (Ndufc2) involved in OXPHOS complex I assembly and activity and the second one (UCP2) involved in clearance of mitochondrial ROS, are responsible, when dysregulated, for vascular damage in SHRSP. The suitability of SHRSP as a model of human disease represents a promising background for future translation of the experimental findings to human hypertension. Novel therapeutic strategies toward mitochondrial molecular targets may become a valuable tool for prevention and treatment of TOD in human hypertension. Speranza Rubattu, Rosita Stanzione, and Massimo Volpe Copyright © 2016 Speranza Rubattu et al. All rights reserved. An Update of Microsomal Prostaglandin E Synthase-1 and PGE2 Receptors in Cardiovascular Health and Diseases Tue, 09 Aug 2016 13:35:53 +0000 http://www.hindawi.com/journals/omcl/2016/5249086/ Nonsteroidal anti-inflammatory drugs (NSAIDs), especially cyclooxygenase-2 (COX-2) selective inhibitors, are among the most widely used drugs to treat pain and inflammation. However, clinical trials have revealed that these inhibitors predisposed patients to a significantly increased cardiovascular risk, consisting of thrombosis, hypertension, myocardial infarction, heart failure, and sudden cardiac death. Thus, microsomal prostaglandin E (PGE) synthase-1 (mPGES-1), the key terminal enzyme involved in the synthesis of inflammatory prostaglandin E2 (PGE2), and the four PGE2 receptors (EP1–4) have gained much attention as alternative targets for the development of novel analgesics. The cardiovascular consequences of targeting mPGES-1 and the PGE2 receptors are substantially studied. Inhibition of mPGES-1 has displayed a relatively innocuous or preferable cardiovascular profile. The modulation of the four EP receptors in cardiovascular system is diversely reported as well. In this review, we highlight the most recent advances from our and other studies on the regulation of PGE2, particularly mPGES-1 and the four PGE2 receptors, in cardiovascular function, with a particular emphasis on blood pressure regulation, atherosclerosis, thrombosis, and myocardial infarction. This might lead to new avenues to improve cardiovascular disease management strategies and to seek optimized anti-inflammatory therapeutic options. Guangrui Yang and Lihong Chen Copyright © 2016 Guangrui Yang and Lihong Chen. All rights reserved. Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways Tue, 09 Aug 2016 07:16:47 +0000 http://www.hindawi.com/journals/omcl/2016/6967396/ The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways. Kang Li, Luobu Gesang, Zeng Dan, and Lamu Gusang Copyright © 2016 Kang Li et al. All rights reserved. Short-Term Effects of Chlorpromazine on Oxidative Stress in Erythrocyte Functionality: Activation of Metabolism and Membrane Perturbation Mon, 08 Aug 2016 16:35:28 +0000 http://www.hindawi.com/journals/omcl/2016/2394130/ The purpose of this paper is to focus on the short-term effects of chlorpromazine on erythrocytes because it is reported that the drug, unstable in plasma but more stable in erythrocytes, interacts with erythrocyte membranes, membrane lipids, and hemoglobin. There is a rich literature about the side and therapeutic effects or complications due to chlorpromazine, but most of these studies explore the influence of long-term treatment. We think that evaluating the short-term effects of the drug may help to clarify the sequence of chlorpromazine molecular targets from which some long-term effects derive. Our results indicate that although the drug is primarily intercalated in the innermost side of the membrane, it does not influence band 3 anionic flux, lipid peroxidation, and protein carbonylation processes. On the other hand, it destabilizes and increases the autooxidation of haemoglobin, induces activation of caspase 3, and, markedly, influences the ATP and reduced glutathione levels, with subsequent exposure of phosphatidylserine at the erythrocyte surface. Overall our observations on the early stage of chlorpromazine influence on erythrocytes may contribute to better understanding of new and interesting characteristics of this compound improving knowledge of erythrocyte metabolism. Silvana Ficarra, Annamaria Russo, Davide Barreca, Elena Giunta, Antonio Galtieri, and Ester Tellone Copyright © 2016 Silvana Ficarra et al. All rights reserved.