Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Impact of Antioxidants on Cardiolipin Oxidation in Liposomes: Why Mitochondrial Cardiolipin Serves as an Apoptotic Signal? Thu, 26 May 2016 10:42:37 +0000 http://www.hindawi.com/journals/omcl/2016/8679469/ Molecules of mitochondrial cardiolipin (CL) get selectively oxidized upon oxidative stress, which triggers the intrinsic apoptotic pathway. In a chemical model most closely resembling the mitochondrial membrane—liposomes of pure bovine heart CL—we compared ubiquinol-10, ubiquinol-6, and alpha-tocopherol, the most widespread naturally occurring antioxidants, with man-made, quinol-based amphiphilic antioxidants. Lipid peroxidation was induced by addition of an azo initiator in the absence and presence of diverse antioxidants, respectively. The kinetics of CL oxidation was monitored via formation of conjugated dienes at 234 nm. We found that natural ubiquinols and ubiquinol-based amphiphilic antioxidants were equally efficient in protecting CL liposomes from peroxidation; the chromanol-based antioxidants, including alpha-tocopherol, were 2-3 times less efficient. Amphiphilic antioxidants, but not natural ubiquinols and alpha-tocopherol, were able, additionally, to protect the CL bilayer from oxidation by acting from the water phase. We suggest that the previously reported therapeutic efficiency of mitochondrially targeted amphiphilic antioxidants is owing to their ability to protect those CL molecules that are inaccessible to natural hydrophobic antioxidants, being trapped within respiratory supercomplexes. The high susceptibility of such occluded CL molecules to oxidation may have prompted their recruitment as apoptotic signaling molecules by nature. Alexey V. Lokhmatikov, Natalia Voskoboynikova, Dmitry A. Cherepanov, Maxim V. Skulachev, Heinz-Jürgen Steinhoff, Vladimir P. Skulachev, and Armen Y. Mulkidjanian Copyright © 2016 Alexey V. Lokhmatikov et al. All rights reserved. Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye Thu, 26 May 2016 07:26:59 +0000 http://www.hindawi.com/journals/omcl/2016/4727415/ Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (). Conclusions. Topical application of 0.1% medicinal plant extracts improved clinical signs, decreased inflammation, and ameliorated oxidative stress marker and ROS production on the ocular surface of the EDE model mice. Won Choi, Jee Bum Lee, Lian Cui, Ying Li, Zhengri Li, Ji Suk Choi, Hyo Seok Lee, and Kyung Chul Yoon Copyright © 2016 Won Choi et al. All rights reserved. Resveratrol: A Potential Hippocampal Plasticity Enhancer Wed, 25 May 2016 11:45:42 +0000 http://www.hindawi.com/journals/omcl/2016/9651236/ The search for molecules capable of restoring altered hippocampal plasticity in psychiatric and neurological conditions is one of the most important tasks of modern neuroscience. It is well established that neural plasticity, such as the ability of the postnatal hippocampus to continuously generate newly functional neurons throughout life, a process called adult hippocampal neurogenesis (AHN), can be modulated not only by pharmacological agents, physical exercise, and environmental enrichment, but also by “nutraceutical” agents. In this review we focus on resveratrol, a phenol and phytoalexin found in the skin of grapes and red berries, as well as in nuts. Resveratrol has been reported to have antioxidant and antitumor properties, but its effects as a neural plasticity inducer are still debated. The current review examines recent evidence implicating resveratrol in regulating hippocampal neural plasticity and in mitigating the effects of various disorders and diseases on this important brain structure. Overall, findings show that resveratrol can improve cognition and mood and enhance hippocampal plasticity and AHN; however, some studies report opposite effects, with resveratrol inhibiting aspects of AHN. Therefore, further investigation is needed to resolve these controversies before resveratrol can be established as a safe coadjuvant in preventing and treating neuropsychiatric conditions. Gisele Pereira Dias, Graham Cocks, Mário Cesar do Nascimento Bevilaqua, Antonio Egidio Nardi, and Sandrine Thuret Copyright © 2016 Gisele Pereira Dias et al. All rights reserved. RAGE Expression and ROS Generation in Neurons: Differentiation versus Damage Wed, 25 May 2016 07:02:27 +0000 http://www.hindawi.com/journals/omcl/2016/9348651/ RAGE is a multiligand receptor able to bind advanced glycation end-products (AGEs), amphoterin, calgranulins, and amyloid-beta peptides, identified in many tissues and cells, including neurons. RAGE stimulation induces the generation of reactive oxygen species (ROS) mainly through the activity of NADPH oxidases. In neuronal cells, RAGE-induced ROS generation is able to favor cell survival and differentiation or to induce death through the imbalance of redox state. The dual nature of RAGE signaling in neurons depends not only on the intensity of RAGE activation but also on the ability of RAGE-bearing cells to adapt to ROS generation. In this review we highlight these aspects of RAGE signaling regulation in neuronal cells. S. Piras, A. L. Furfaro, C. Domenicotti, N. Traverso, U. M. Marinari, M. A. Pronzato, and M. Nitti Copyright © 2016 S. Piras et al. All rights reserved. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited Wed, 25 May 2016 06:31:48 +0000 http://www.hindawi.com/journals/omcl/2016/1656450/ Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions. Gino A. Kurian, Rashmi Rajagopal, Srinivasan Vedantham, and Mohanraj Rajesh Copyright © 2016 Gino A. Kurian et al. All rights reserved. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarker Wed, 25 May 2016 06:18:29 +0000 http://www.hindawi.com/journals/omcl/2016/3592042/ Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients’ burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker’s potential to predict clinical outcomes. Nicole Schupp, Helga Stopper, and August Heidland Copyright © 2016 Nicole Schupp et al. All rights reserved. Quantitative Assessment of the Effects of Oxidants on Antigen-Antibody Binding In Vitro Tue, 24 May 2016 12:17:47 +0000 http://www.hindawi.com/journals/omcl/2016/1480463/ Objective. We quantitatively assessed the influence of oxidants on antigen-antibody-binding activity. Methods. We used several immunological detection methods, including precipitation reactions, agglutination reactions, and enzyme immunoassays, to determine antibody activity. The oxidation-reduction potential was measured in order to determine total serum antioxidant capacity. Results. Certain concentrations of oxidants resulted in significant inhibition of antibody activity but had little influence on total serum antioxidant capacity. Conclusions. Oxidants had a significant influence on interactions between antigen and antibody, but minimal effect on the peptide of the antibody molecule. Shuang Han, Guanyu Wang, Naijin Xu, and Hui Liu Copyright © 2016 Shuang Han et al. All rights reserved. Corrigendum to “Glucose Oxidase Induces Cellular Senescence in Immortal Renal Cells through ILK by Downregulating Klotho Gene Expression” Tue, 24 May 2016 11:27:51 +0000 http://www.hindawi.com/journals/omcl/2016/8392708/ Nuria Troyano-Suárez, María del Nogal-Avila, Inés Mora, Patricia Sosa, Susana López-Ongil, Diego Rodriguez-Puyol, Gemma Olmos, and María Piedad Ruíz-Torres Copyright © 2016 Nuria Troyano-Suárez et al. All rights reserved. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury Tue, 24 May 2016 06:26:56 +0000 http://www.hindawi.com/journals/omcl/2016/2950503/ Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury. Aleksandra Kezic, Ivan Spasojevic, Visnja Lezaic, and Milica Bajcetic Copyright © 2016 Aleksandra Kezic et al. All rights reserved. Endothelial Microparticle-Derived Reactive Oxygen Species: Role in Endothelial Signaling and Vascular Function Mon, 23 May 2016 09:10:51 +0000 http://www.hindawi.com/journals/omcl/2016/5047954/ Endothelial microparticles are effectors of endothelial damage; however mechanisms involved are unclear. We examined the effects of eMPs on cultured endothelial cells (ECs) and isolated vessels and investigated the role of eMP-derived reactive oxygen species (ROS) and redox signaling in these processes. eMPs were isolated from EC media and their ability to directly produce ROS was assessed by lucigenin and liquid chromatography. Nicotinamide adenine dinucleotide phosphate oxidase (Nox) subunits were probed by Western blot. ECs were treated with eMPs and effects on kinase signaling, superoxide anion () generation, and nitric oxide (NO) production were examined. Acetylcholine-mediated vasorelaxation was assessed by myography in eMP-treated mesenteric arteries. eMPs contained Nox1, Nox2, Nox4, p4, p6, and p2 and they produced ROS which was inhibited by the Nox inhibitor, apocynin. eMPs increased phosphorylation of ERK1/2 and Src, increased production, and decreased A23187-induced NO production in ECs. Pretreatment of eMPs with apocynin diminished eMP-mediated effects on ROS and NO production but had no effect on eMP-mediated kinase activation or impairment in vasorelaxation. Our findings identify a novel mechanism whereby eMP-derived ROS contributes to MP bioactivity. These interactions may be important in conditions associated with vascular injury and increased eMP formation. Dylan Burger, Maddison Turner, Mercedes N. Munkonda, and Rhian M. Touyz Copyright © 2016 Dylan Burger et al. All rights reserved. Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity Mon, 23 May 2016 07:40:40 +0000 http://www.hindawi.com/journals/omcl/2016/5724973/ Doxorubicin (DOX) is a potent and widely used anthracycline antibiotic for the treatment of several malignancies. Unfortunately, the clinical utility of DOX is often restricted due to the elicitation of organ toxicity. Particularly, the increased risk for the development of dilated cardiomyopathy by DOX among the cancer survivors warrants major attention from the physicians as well as researchers to develop adjuvant agents to neutralize the noxious effects of DOX on the healthy myocardium. Despite these pitfalls, the use of traditional cytotoxic drugs continues to be the mainstay treatment for several types of cancer. Recently, phytochemicals have gained attention for their anticancer, chemopreventive, and cardioprotective activities. The ideal cardioprotective agents should not compromise the clinical efficacy of DOX and should be devoid of cumulative or irreversible toxicity on the naïve tissues. Furthermore, adjuvants possessing synergistic anticancer activity and quelling of chemoresistance would significantly enhance the clinical utility in combating DOX-induced cardiotoxicity. The present review renders an overview of cardioprotective effects of plant-derived small molecules and their purported mechanisms against DOX-induced cardiotoxicity. Phytochemicals serve as the reservoirs of pharmacophore which can be utilized as templates for developing safe and potential novel cardioprotective agents in combating DOX-induced cardiotoxicity. Shreesh Ojha, Hasan Al Taee, Sameer Goyal, Umesh B. Mahajan, Chandrgouda R. Patil, D. S. Arya, and Mohanraj Rajesh Copyright © 2016 Shreesh Ojha et al. All rights reserved. S-Propargyl-cysteine Exerts a Novel Protective Effect on Methionine and Choline Deficient Diet-Induced Fatty Liver via Akt/Nrf2/HO-1 Pathway Sun, 22 May 2016 10:03:49 +0000 http://www.hindawi.com/journals/omcl/2016/4690857/ This study investigated the antioxidative effect of S-propargyl-cysteine (SPRC) on nonalcoholic fatty liver (NAFLD) by treating mice fed a methionine and choline deficient (MCD) diet with SPRC for four weeks. We found that SPRC significantly reduced hepatic reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels. Moreover, SPRC also increased the superoxide dismutase (SOD) activity. By Western blot, we found that this protective effect of SPRC was importantly attributed to the regulated hepatic antioxidant-related proteins, including protein kinase B (Akt), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cystathionine γ-lyase (CSE, an enzyme that synthesizes hydrogen sulfide). Next, we examined the detailed molecular mechanism of the SPRC protective effect using oleic acid- (OA-) induced HepG2 cells. The results showed that SPRC significantly decreased intracellular ROS and MDA levels in OA-induced HepG2 cells by upregulating the phosphorylation of Akt, the expression of HO-1 and CSE, and the translocation of Nrf2. SPRC-induced HO-1 expression and Nrf2 translocation were abolished by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Moreover, the antioxidative effect of SPRC was abolished by CSE inhibitor DL-propargylglycine (PAG) and HO-1 siRNA. Therefore, these results proved that SPRC produced an antioxidative effect on NAFLD through the PI3K/Akt/Nrf2/HO-1 signaling pathway. Wenwen Li, Fenfen Ma, Laiyin Zhang, Yong Huang, Xinghui Li, Aijie Zhang, Cuilan Hou, Yichun Zhu, and YiZhun Zhu Copyright © 2016 Wenwen Li et al. All rights reserved. Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator Thu, 19 May 2016 11:41:46 +0000 http://www.hindawi.com/journals/omcl/2016/5290638/ Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. Louise D. Zheng, Leah E. Linarelli, Joseph Brooke, Cayleen Smith, Sarah S. Wall, Mark H. Greenawald, Richard W. Seidel, Paul A. Estabrooks, Fabio A. Almeida, and Zhiyong Cheng Copyright © 2016 Louise D. Zheng et al. All rights reserved. Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis Wed, 18 May 2016 14:24:05 +0000 http://www.hindawi.com/journals/omcl/2016/8703645/ Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was tested in vivo to prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25–1.25 nmol/kg/day (0.13–0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophils in vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis. Alexander A. Andreev-Andrievskiy, Nataliya G. Kolosova, Natalia A. Stefanova, Maxim V. Lovat, Maxim V. Egorov, Vasily N. Manskikh, Roman A. Zinovkin, Ivan I. Galkin, Anastasia S. Prikhodko, Maxim V. Skulachev, and Alexander N. Lukashev Copyright © 2016 Alexander A. Andreev-Andrievskiy et al. All rights reserved. Neuroprotection of Grape Seed Extract and Pyridoxine against Triton-Induced Neurotoxicity Mon, 16 May 2016 11:07:18 +0000 http://www.hindawi.com/journals/omcl/2016/8679506/ Triton WR-1339 administration causes neurotoxicity. Natural products and herbal extracts can attenuate cerebral injury. In the present study, we investigated the neuroprotective role of grape seed extract and/or vitamin B6 against triton-induced neurotoxicity. Thirty-five adult male albino rats of the Sprague-Dawley strain, weighing 140–145 g, were divided into five groups: control, triton, grape seed extract + triton, grape seed extract + triton + vitamin B6, and vitamin B6 + triton. The hematological and biochemical analyses were carried out. Alteration in iNOS mRNA gene expression was determined using reverse-transcriptase PCR analysis. In addition, qualitative DNA fragmentation was examined using agarose gel electrophoresis. Triton-treatment caused significant disturbances in the hematological parameters, the neurological functions, and the antioxidant profile. Also, triton significantly increased the iNOS mRNA expression and DNA damage. Our results showed that grape seed extract and/or vitamin B6 could attenuate all the examined parameters. These natural substances could exhibit protective effects against triton-induced neurological damage because of their antioxidative and antiapoptotic capacities. Heba M. Abdou and Mayssaa M. Wahby Copyright © 2016 Heba M. Abdou and Mayssaa M. Wahby. All rights reserved. Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective Mon, 16 May 2016 09:00:40 +0000 http://www.hindawi.com/journals/omcl/2016/8215082/ The morbidity and mortality of obstructive sleep apnea-hypopnea syndrome (OSAHS) are regarded as consequences of its adverse effects on the cardiovascular system. Chronic intermittent hypoxia (CIH) induced by OSAHS can result in vascular endothelial injury, thus promoting development of atherosclerosis (AS). Studies have shown that CIH is an independent risk factor for the occurrence and development of AS, but the underlying mechanism remains unclear. Here, we review clinical and fundamental studies reported during the last 10 years on the occurrence and development of AS mediated by CIH, focusing on inflammation, oxidative stress, insulin resistance, cell apoptosis, vascular endothelial injury, platelet activation, and neuroendocrine disorders. This review will offer current evidence and perspective to researchers for the development of effective intervention strategies for OSAHS-related cardiocerebrovascular diseases. Linqin Ma, Jingchun Zhang, and Yue Liu Copyright © 2016 Linqin Ma et al. All rights reserved. Oxidative Stress and Cancer: Advances and Challenges Mon, 16 May 2016 08:27:03 +0000 http://www.hindawi.com/journals/omcl/2016/5010423/ Sahdeo Prasad, Subash C. Gupta, Manoj K. Pandey, Amit K. Tyagi, and Lokesh Deb Copyright © 2016 Sahdeo Prasad et al. All rights reserved. Antioxidants and Polyphenols: Concentrations and Relation to Male Infertility and Treatment Success Thu, 12 May 2016 13:41:59 +0000 http://www.hindawi.com/journals/omcl/2016/9140925/ Oxidative stress is induced by reactive oxygen substances (ROS) that are known to affect male fertility. The aims of this study were to prospectively investigate and characterize total antioxidant and specifically polyphenols concentrations and their relations to sperm quality and fertility treatment success. During their infertility treatment, sixty-seven males were prospectively recruited to this study. After separation of the sperm from the semen sample, the semen fluid samples antioxidants and polyphenols concentrations were determined. Antioxidant concentration was significantly associated with sperm concentration and total motile count. Antioxidants concentration in the group of male with sperm concentration ≥ 15 × 106 was significantly higher than in the group of male with antioxidants concentration < 15 × 106 (830.3 ± 350 μM and 268.3 ± 220 μM, resp., ). Polyphenols concentration did not differ between the groups of sperm concentration above and below 15 × 106 (178.7 ± 121 μM and 161.7 ± 61 μM, resp., -NS). No difference was found between fertilization rates and antioxidants or polyphenols concentrations. This is the first study that reports on polyphenols concentration within semen fluid. More studies are needed in order to investigate polyphenols role in male fertility. Tali Silberstein, Iris Har-Vardi, Avi Harlev, Michael Friger, Batel Hamou, Tamar Barac, Eli Levitas, and Oshra Saphier Copyright © 2016 Tali Silberstein et al. All rights reserved. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy Thu, 12 May 2016 10:54:03 +0000 http://www.hindawi.com/journals/omcl/2016/7425628/ About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis. Khadija Rebbani and Kyoko Tsukiyama-Kohara Copyright © 2016 Khadija Rebbani and Kyoko Tsukiyama-Kohara. All rights reserved. The Injury and Therapy of Reactive Oxygen Species in Intracerebral Hemorrhage Looking at Mitochondria Thu, 12 May 2016 07:58:56 +0000 http://www.hindawi.com/journals/omcl/2016/2592935/ Intracerebral hemorrhage is an emerging major health problem often resulting in death or disability. Reactive oxygen species (ROS) have been identified as one of the major damaging factors in ischemic stroke. However, there is less discussion about ROS in hemorrhage stroke. Metabolic products of hemoglobin, excitatory amino acids, and inflammatory cells are all sources of ROS, and ROS harm the central nervous system through cell death and structural damage, especially disruption of the blood-brain barrier. We have considered the antioxidant system of the CNS itself and the drugs aiming to decrease ROS after ICH, and we find that mitochondria are key players in all of these aspects. Moreover, when the mitochondrial permeability transition pore opens, ROS-induced ROS release, which leads to extensive liberation of ROS and mitochondrial failure, occurs. Therefore, the mitochondrion may be a significant target for elucidating the problem of ROS in ICH; however, additional experimental support is required. Jie Qu, Weixiang Chen, Rong Hu, and Hua Feng Copyright © 2016 Jie Qu et al. All rights reserved. Extracellular Superoxide Dismutase: Growth Promoter or Tumor Suppressor? Thu, 12 May 2016 07:57:53 +0000 http://www.hindawi.com/journals/omcl/2016/3612589/ Extracellular superoxide dismutase (SOD3) gene transfer to tissue damage results in increased healing, increased cell proliferation, decreased apoptosis, and decreased inflammatory cell infiltration. At molecular level, in vivo SOD3 overexpression reduces superoxide anion () concentration and increases mitogen kinase activation suggesting that SOD3 could have life-supporting characteristics. The hypothesis is further strengthened by the observations showing significantly increased mortality in conditional knockout mice. However, in cancer SOD3 has been shown to either increase or decrease cell proliferation and survival depending on the model system used, indicating that SOD3-derived growth mechanisms are not completely understood. In this paper, the author reviews the main discoveries in SOD3-dependent growth regulation and signal transduction. Mikko O. Laukkanen Copyright © 2016 Mikko O. Laukkanen. All rights reserved. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases Tue, 10 May 2016 10:43:25 +0000 http://www.hindawi.com/journals/omcl/2016/3565127/ The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging. Pierpaola Davalli, Tijana Mitic, Andrea Caporali, Angela Lauriola, and Domenico D’Arca Copyright © 2016 Pierpaola Davalli et al. All rights reserved. Antioxidant and Hypolipidemic Activity of the Hydroethanolic Extract of Curatella americana L. Leaves Mon, 09 May 2016 14:59:04 +0000 http://www.hindawi.com/journals/omcl/2016/9681425/ High levels of reactive oxygen species in the body and hyperlipidemia are key factors for the development of cardiovascular diseases such as atherosclerosis. The present study investigated the antioxidant and hypolipidemic activity of hydroethanolic extract of Curatella americana L. leaves (ExC). The antioxidant activity of ExC was assessed by 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging capacity and protection against hemolysis induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), followed by quantification of malondialdehyde (MDA). Wistar rats with hyperlipidemia induced by high-fructose diet (60%) were treated for 60 days with water, simvastatin (30 mg·Kg−1), ciprofibrate (2 mg·Kg−1), and ExC (200 mg·Kg−1). ExC revealed IC50 of  μg·mL−1, an intermediary value among positive controls used in the assay of DPPH scavenging capacity. At all concentrations (50 to 125 μg·mL−1) and times (60 to 240 min) evaluated, ExC protected erythrocytes against AAPH-induced hemolysis, which was confirmed by lower MDA levels. In vivo tests showed a reduction of 34 and 45%, respectively, in serum concentration of cholesterol and triglycerides in hyperlipidemic rats treated with ExC, a similar effect compared to the reference drugs, simvastatin and ciprofibrate, respectively. Together, the results showed the antioxidant activity of ExC and its ability to improve the serum lipid profile in hyperlipidemic rats. Rafael Henrique Oliveira Lopes, Luis Fernando Benitez Macorini, Katia Ávila Antunes, Priscilla Pereira de Toledo Espindola, Tamaeh Monteiro Alfredo, Paola dos Santos da Rocha, Zefa Valdivina Pereira, Edson Lucas dos Santos, and Kely de Picoli Souza Copyright © 2016 Rafael Henrique Oliveira Lopes et al. All rights reserved. (Z)-5-(2,4-Dihydroxybenzylidene)thiazolidine-2,4-dione Prevents UVB-Induced Melanogenesis and Wrinkle Formation through Suppressing Oxidative Stress in HRM-2 Hairless Mice Sun, 08 May 2016 14:28:49 +0000 http://www.hindawi.com/journals/omcl/2016/2761463/ Background. Uncontrolled melanogenesis and wrinkle formation are an indication of photoaging. Our previous studies demonstrated that (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498) inhibited tyrosinase activity and melanogenesis in vitro. Objective. To examine in vivo effects of MHY498 as an antiaging compound on UVB-induced melanogenesis and wrinkle formation, we topically applied MHY498 on dorsal skin of HRM-2 hairless mice. Methods. Using histological analysis, we evaluated effects of MHY498 on melanogenesis and wrinkle formation after UVB exposure. In addition, related molecular signaling pathways were examined using western blotting, fluorometric assay, and enzyme-linked immunosorbent assay. Results. MHY498 suppressed UVB-induced melanogenesis by inhibiting phosphorylation of CREB and translocation of MITF protein into the nucleus, which are key factors for tyrosinase expression. Consistently, tyrosinase protein levels were notably reduced in the dorsal skin of the hairless mice by MHY498 treatment. Furthermore, MHY498 inhibited UVB-induced wrinkle formation and collagen fiber destruction by increasing type 1 procollagen concentration and decreasing protein expression levels of MMPs, which play an essential role in collagen fiber degradation. As a mechanism, MHY498 notably ameliorated UVB-induced oxidative stress and NF-κB activation in the dermal skin of the hairless mice. Conclusion. Our study suggests that MHY498 can be used as a therapeutic or cosmetic agent for preventing uncontrolled melanogenesis and wrinkle formation. Bonggi Lee, Kyoung Mi Moon, Seong Jin Kim, So Hee Kim, Dae Hyun Kim, Hye Jin An, Ji Won Jeong, Ye Ra Kim, Sujin Son, Min Jo Kim, Ki Wung Chung, Eun Kyeong Lee, Pusoon Chun, Young Mi Ha, Min-Sun Kim, Sang Hyun Mo, Hyung Ryong Moon, and Hae Young Chung Copyright © 2016 Bonggi Lee et al. All rights reserved. Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression Thu, 05 May 2016 16:29:40 +0000 http://www.hindawi.com/journals/omcl/2016/1874762/ The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms. Nagla A. El-Shitany and Karema El-Desoky Copyright © 2016 Nagla A. El-Shitany and Karema El-Desoky. All rights reserved. An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia Thu, 05 May 2016 07:45:42 +0000 http://www.hindawi.com/journals/omcl/2016/9162074/ In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers. Mengting Liu, Liying Tang, Xin Liu, Jing Fang, Hao Zhan, Hongwei Wu, and Hongjun Yang Copyright © 2016 Mengting Liu et al. All rights reserved. Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats Wed, 04 May 2016 16:37:46 +0000 http://www.hindawi.com/journals/omcl/2016/9685257/ Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM) in diet-streptozotocin- (STZ-) induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-β-d-glucosaminidase verified CM’s renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3β in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats. Chungang Liu, Jingjing Song, Meiyu Teng, Xiaoyi Zheng, Xiangmei Li, Yue Tian, Minlian Pan, Yuhuan Li, Robert J. Lee, and Di Wang Copyright © 2016 Chungang Liu et al. All rights reserved. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation Wed, 04 May 2016 11:27:18 +0000 http://www.hindawi.com/journals/omcl/2016/4650489/ Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior () was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic. Maximilian Weniger, Leonard Reinelt, Jens Neumann, Lesca Holdt, Matthias Ilmer, Bernhard Renz, Werner Hartwig, Jens Werner, Alexandr V. Bazhin, and Jan G. D’Haese Copyright © 2016 Maximilian Weniger et al. All rights reserved. Association of Nuclear Factor-Erythroid 2-Related Factor 2, Thioredoxin Interacting Protein, and Heme Oxygenase-1 Gene Polymorphisms with Diabetes and Obesity in Mexican Patients Wed, 04 May 2016 07:15:06 +0000 http://www.hindawi.com/journals/omcl/2016/7367641/ The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H:quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, ) and in women (CC versus CT + TT, OR = 0.7, ). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, ). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, ). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients. Angélica Saraí Jiménez-Osorio, Susana González-Reyes, Wylly Ramsés García-Niño, Hortensia Moreno-Macías, Martha Eunice Rodríguez-Arellano, Gilberto Vargas-Alarcón, Joaquín Zúñiga, Rodrigo Barquera, and José Pedraza-Chaverri Copyright © 2016 Angélica Saraí Jiménez-Osorio et al. 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.