Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Nitric Oxide Synthetic Pathway in Patients with Microvascular Angina and Its Relations with Oxidative Stress Tue, 22 Apr 2014 08:46:36 +0000 http://www.hindawi.com/journals/omcl/2014/726539/ A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis. Benedetta Porro, Sonia Eligini, Fabrizio Veglia, Alessandro Lualdi, Isabella Squellerio, Susanna Fiorelli, Marta Giovannardi, Elisa Chiorino, Alessia Dalla Cia, Mauro Crisci, José Pablo Werba, Elena Tremoli, and Viviana Cavalca Copyright © 2014 Benedetta Porro et al. All rights reserved. Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction Tue, 22 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/283180/ Nitric oxide (NO) deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR) rats, controls treated with melatonin (0.01% in drinking water), and CR rats treated with melatonin (CR + M). The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor), decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR), and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes. You-Lin Tain, Li-Tung Huang, Chien-Ning Hsu, and Chien-Te Lee Copyright © 2014 You-Lin Tain et al. All rights reserved. Physical Exercise Combined with Whole-Body Cryotherapy in Evaluating the Level of Lipid Peroxidation Products and Other Oxidant Stress Indicators in Kayakers Thu, 17 Apr 2014 06:08:16 +0000 http://www.hindawi.com/journals/omcl/2014/402631/ The influence of exercise combined with whole-body cryotherapy (WBC) on the oxidant/antioxidant balance in healthy men was assessed. The study included 16 kayakers of the Polish National Team, aged 22.7 ± 2.6, subjected to WBC (−120°C–−145°C; 3 min) twice a day for the first 10 days of a 19-day physical training cycle: pre exercise morning stimulation and post exercise afternoon recovery. Blood samples were taken on Day 0 (baseline) and on Days 5, 11 and 19. The serum concentration of malondialdehyde (MDA), conjugated dienes (CD), thiobarbituric acid reactive substances (TBARS), protein carbonyls, vitamin E, urea, cortisol, and testosterone were determined, along with the glutathione peroxidase (GPx) activity, the total antioxidant capacity (TAC), and morphological blood parameters. On 5th day of exercise/WBC, the baseline GPx activity decreased by 15.1% (), while on 19th day, it increased by 19.7% () versus Day 5. On Day 19 TBARS concentration decreased versus baseline and Day 5 (by 15.9% and 17.4%, resp.; ). On 19 Day urea concentration also decreased versus 11 Day; however, on 5th and 11th days the level was higher versus baseline. Combining exercise during longer training cycles with WBC may be advantageous. Paweł Sutkowy, Beata Augustyńska, Alina Woźniak, and Andrzej Rakowski Copyright © 2014 Paweł Sutkowy et al. All rights reserved. Effect of Centella asiatica on Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models Wed, 16 Apr 2014 10:59:36 +0000 http://www.hindawi.com/journals/omcl/2014/154295/ Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) of Centella asiatica had a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction of Centella asiatica has antioxidant and hypolipidemic properties. Yun Zhao, Ping Shu, Youzhi Zhang, Limin Lin, Haihong Zhou, Zhentian Xu, Daqin Suo, Anzhi Xie, and Xin Jin Copyright © 2014 Yun Zhao et al. All rights reserved. New Insights into the Steen Solution Properties: Breakthrough in Antioxidant Effects via NOX2 Downregulation Wed, 16 Apr 2014 08:55:07 +0000 http://www.hindawi.com/journals/omcl/2014/242180/ Ex vivo lung perfusion (EVLP) allows perfusion and reconditioning of retrieved lungs for organ transplantation. The Steen solution is specifically designed for this procedure but the mechanism through which it elicits its activity is still to be fully clarified. We speculated that Steen solution may encompass antioxidant properties allowing a reestablishment of pulmonary tissue homeostasis. Blood samples from 10 healthy volunteers were recruited. Platelets and white cells were incubated with Steen solution or buffer solution as control and stimulated with suitable agonists. Reactive oxidant species (ROS), soluble NOX2 (sNOX2-derived peptide), a marker of NADPH oxidase activation, translocation to cell membrane and isoprostanes production, as marker of oxidative stress, and nitric oxide (NO), a powerful vasodilator and antioxidant molecule, were measured upon cell stimulation. The Steen solution significantly inhibited translocation and NOX2 activation in platelets and white cells. Consistent with this finding was the reduction of oxidative stress as documented by a significantly lowered formation of ROS and isoprostanes by both platelets and white cells. Finally, cell incubation with Steen solution resulted in enhanced generation of NO. Herewith, we provide the first evidence that Steen solution possesses antioxidant properties via downregulation of NADPH oxidase activity and enhanced production of NO. Roberto Carnevale, Giuseppe Biondi-Zoccai, Mariangela Peruzzi, Elena De Falco, Isotta Chimenti, Federico Venuta, Marco Anile, Daniele Diso, Elena Cavarretta, Antonino G. M. Marullo, Patrizio Sartini, Pasquale Pignatelli, Francesco Violi, and Giacomo Frati Copyright © 2014 Roberto Carnevale et al. All rights reserved. Leptin Level and Oxidative Stress Contribute to Obesity-Induced Low Testosterone in Murine Testicular Tissue Mon, 14 Apr 2014 07:27:00 +0000 http://www.hindawi.com/journals/omcl/2014/190945/ Objective. This study evaluated the effects of obesity on the function of reproductive organs in male mice and the possible mechanism of male secondary hypogonadism (SH) in obesity. Methods. Ninety-six mice were randomly assigned to three groups: the control group, diet-induced obesity group, and diet-induced obesity resistant group for 8 weeks and 19 weeks. The effects of short- and long-term high-fat diet on the reproductive organs were determined by measuring sperm count and motility, relative testis weight, testosterone level, pathological changes and apoptosis of Leydig cells. Oxidative stress was evaluated by determining malondialdehyde, H2O2, NO levels, and GSH in testis tissues. CAT, SOD, GSH-Px and Nrf2 mRNA were measured by real-time PCR. Results. Short- and long-term high-fat diet decreased sperm count and motility, relative testis weight, testosterone level; decreased CAT, SOD, GSH-Px and Nrf2 mRNA expression; increased MDA, H2O2, NO and leptin levels; inhibited the activity of CAT and GSH-Px enzymes. Pathological injury and apoptosis of Leydig cells were found in testis tissue. Conclusions. Pathological damage of Leydig cells, oxidative stress in testis tissue, and high level of leptin may provide some evidence to clarify the mechanisms of male SH in obesity. Jian Zhao, Lingling Zhai, Zheng Liu, Shuang Wu, and Liping Xu Copyright © 2014 Jian Zhao et al. All rights reserved. Endogenous Ceramide Contributes to the Transcytosis of oxLDL across Endothelial Cells and Promotes Its Subendothelial Retention in Vascular Wall Thu, 10 Apr 2014 14:10:56 +0000 http://www.hindawi.com/journals/omcl/2014/823071/ Oxidized low density of lipoprotein (oxLDL) is the major lipid found in atherosclerotic lesion and elevated plasma oxLDL is recognized to be a risk factor of atherosclerosis. Whether plasma oxLDL could be transported across endothelial cells and initiate atherosclerotic changes remains unknown. In an established in vitro cellular transcytosis model, the present study found that oxLDL could traffic across vascular endothelial cells and further that the regulation of endogenous ceramide production by ceramide metabolizing enzyme inhibitors significantly altered the transcytosis of oxLDL across endothelial cells. It was found that acid sphingomyelinase inhibitor, desipramine (DES), and de novo ceramide synthesis inhibitor, myriocin (MYR), both decreasing the endogenous ceramide production, significantly inhibited the transcytosis of oxLDL. Ceramidase inhibitor, N-oleoylethanolamine (NOE), and sphingomyelin synthase inhibitor, O-Tricyclo[5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt (D609), both increasing the endogenous ceramide production, significantly upregulated the transcytosis of oxLDL. In vivo, injection of fluorescence labeled oxLDL into mice body also predisposed to the subendothelial retention of these oxidized lipids. The observations provided in the present study demonstrate that endogenous ceramide contributes to the transcytosis of oxLDL across endothelial cells and promotes the initiating step of atherosclerosis—the subendothelial retention of lipids in vascular wall. Wenjing Li, Xiaoyan Yang, Shasha Xing, Fang Bian, Wanjing Yao, Xiangli Bai, Tao Zheng, Guangjie Wu, and Si Jin Copyright © 2014 Wenjing Li et al. All rights reserved. Antioxidant Strategies and Respiratory Disease of the Preterm Newborn: An Update Mon, 07 Apr 2014 13:38:45 +0000 http://www.hindawi.com/journals/omcl/2014/721043/ Preterm newborns are challenged by an excessive oxidative burden, as a result of several perinatal stimuli, as intrauterine infections, resuscitation, mechanical ventilation, and postnatal complications, in the presence of immature antioxidant capacities. “Oxygen radical disease of neonatology” comprises a wide range of conditions sharing a common pathway of pathogenesis and includes bronchopulmonary dysplasia (BPD) and other main complications of prematurity. Antioxidant strategies may be beneficial in the prevention and treatment of oxidative stress- (OS-) related lung disease of the preterm newborn. Endotracheal supplementation or lung-targeted overexpression of superoxide dismutase was proved to reduce lung damage in several models; however, the supplementation in preterm newborn failed to reduce the risk of BPD, although long-term respiratory outcomes were improved. Also melatonin administration to small cohorts of preterm newborns suggested beneficial effects on lung OS. The possibility to identify single nucleotide polymorphism affecting the risk of BPD may help to identify specific populations with particularly high risk of OS-related diseases and may pose the basis for individually targeted treatments. Finally, surfactant replacement may lead to local anti-inflammatory and antioxidant effects, thanks to specific enzymatic and nonenzymatic antioxidants naturally present in animal surfactants. Chiara Poggi and Carlo Dani Copyright © 2014 Chiara Poggi and Carlo Dani. All rights reserved. Olive (Olea europaea) Leaf Extract Induces Apoptosis and Monocyte/Macrophage Differentiation in Human Chronic Myelogenous Leukemia K562 Cells: Insight into the Underlying Mechanism Sun, 06 Apr 2014 13:36:54 +0000 http://www.hindawi.com/journals/omcl/2014/927619/ Differentiation therapy is an attractive approach aiming at reversing malignancy and reactivating endogenous differentiation programs in cancer cells. Olive leaf extract, known for its antioxidant activity, has been demonstrated to induce apoptosis in several cancer cells. However, its differentiation inducing properties and the mechanisms involved are still poorly understood. In this study, we investigated the effect of Chemlali Olive Leaf Extract (COLE) for its potential differentiation inducing effect on multipotent leukemia K562 cells. Results showed that COLE inhibits K562 cells proliferation and arrests the cell cycle at G0/G1, and then at G2/M phase over treatment time. Further analysis revealed that COLE induces apoptosis and differentiation of K562 cells toward the monocyte lineage. Microarray analysis was conducted to investigate the underlying mechanism of COLE differentiation inducing effect. The differentially expressed genes such as IFI16, EGR1, NFYA, FOXP1, CXCL2, CXCL3, and CXCL8 confirmed the commitment of K562 cells to the monocyte/macrophage lineage. Thus our results provide evidence that, in addition to apoptosis, induction of differentiation is one of the possible therapeutic effects of olive leaf in cancer cells. Imen Samet, Junkyu Han, Lobna Jlaiel, Sami Sayadi, and Hiroko Isoda Copyright © 2014 Imen Samet et al. All rights reserved. The Production of Nitric Oxide, IL-6, and TNF-Alpha in Palmitate-Stimulated PBMNCs Is Enhanced through Hyperglycemia in Diabetes Sun, 06 Apr 2014 13:21:17 +0000 http://www.hindawi.com/journals/omcl/2014/479587/ We examined nitric oxide (NO), IL-6, and TNF- secretion from cultured palmitate-stimulated PBMNCs or in the plasma from type 2 diabetes mellitus (T2MD) patients or nondiabetic (ND) controls. Free fatty acids (FFA) have been suggested to induce chronic low-grade inflammation, activate the innate immune system, and cause deleterious effects on vascular cells and other tissues through inflammatory processes. The levels of NO, IL-6, TNF-, and MDA were higher in supernatant of palmitate stimulated blood cells (PBMNC) or from plasma from patients. The results obtained in the present study demonstrated that hyperglycemia in diabetes exacerbates in vitro inflammatory responses in PBMNCs stimulated with high levels of SFA (palmitate). These results suggest that hyperglycemia primes PBMNCs for NO, IL-6, and TNF-alpha secretion under in vitro FFA stimulation are associated with the secretion of inflammatory biomarkers in diabetes. A combined therapy targeting signaling pathways activated by hyperglycemia in conjunction with simultaneous control of hyperglycemia and hypertriglyceridemia would be suggested for controlling the progress of diabetic complications. Caroline Maria Oliveira Volpe, Luana Farnese Machado Abreu, Pollyanna Stephanie Gomes, Raquel Miranda Gonzaga, Clara Araújo Veloso, and José Augusto Nogueira-Machado Copyright © 2014 Caroline Maria Oliveira Volpe et al. All rights reserved. Oxidative Stress in Aging Sun, 06 Apr 2014 06:32:43 +0000 http://www.hindawi.com/journals/omcl/2014/876834/ Mohammad Abdollahi, Majid Y. Moridani, Okezie I. Aruoma, and Sara Mostafalou Copyright © 2014 Mohammad Abdollahi et al. All rights reserved. BL153 Partially Prevents High-Fat Diet Induced Liver Damage Probably via Inhibition of Lipid Accumulation, Inflammation, and Oxidative Stress Thu, 03 Apr 2014 16:32:30 +0000 http://www.hindawi.com/journals/omcl/2014/674690/ The present study was to investigate whether a magnolia extract, named BL153, can prevent obesity-induced liver damage and identify the possible protective mechanism. To this end, obese mice were induced by feeding with high fat diet (HFD, 60% kcal as fat) and the age-matched control mice were fed with control diet (10% kcal as fat) for 6 months. Simultaneously these mice were treated with or without BL153 daily at 3 dose levels (2.5, 5, and 10 mg/kg) by gavage. HFD feeding significantly increased the body weight and the liver weight. Administration of BL153 significantly reduced the liver weight but without effects on body weight. As a critical step of the development of NAFLD, hepatic fibrosis was induced in the mice fed with HFD, shown by upregulating the expression of connective tissue growth factor and transforming growth factor beta 1, which were significantly attenuated by BL153 in a dose-dependent manner. Mechanism study revealed that BL153 significantly suppressed HFD induced hepatic lipid accumulation and oxidative stress and slightly prevented liver inflammation. These results suggest that HFD induced fibrosis in the liver can be prevented partially by BL153, probably due to reduction of hepatic lipid accumulation, inflammation and oxidative stress. Jian Wang, Chi Zhang, Zhiguo Zhang, Qiang Chen, Xuemian Lu, Minglong Shao, Liangmiao Chen, Hong Yang, Fangfang Zhang, Peng Cheng, Yi Tan, Ki-Soo Kim, Ki Ho Kim, Bochu Wang, and Young Heui Kim Copyright © 2014 Jian Wang et al. All rights reserved. Psoralea corylifolia L. Seed Extract Ameliorates Streptozotocin-Induced Diabetes in Mice by Inhibition of Oxidative Stress Thu, 03 Apr 2014 13:39:31 +0000 http://www.hindawi.com/journals/omcl/2014/897296/ Pancreatic beta-cell death is known to be the cause of deficient insulin production in diabetes mellitus. Oxidative stress is one of the major causes of beta-cell death. In this study, we investigated the effects of Psoralea corylifolia L. seed (PCS) extract on beta-cell death. Oral administration of PCS extract resulted in a significant improvement of hyperglycemia in streptozotocin-induced diabetic mice. PCS extract treatment improved glucose tolerance and increased serum insulin levels. To study the mechanisms involved, we investigated the effects of PCS extract on H2O2-induced apoptosis in INS-1 cells. Treatment with PCS extract inhibited cell death. PCS extract treatment decreased reactive oxygen species level and activated antioxidative enzymes. Among the major components of PCS extract, psoralen and isopsoralen (coumarins), but not bakuchiol, showed preventive effects against H2O2-induced beta-cell death. These findings indicate that PCS extract may be a potential pharmacological agent to protect against pancreatic beta-cell damage caused by oxidative stress associated with diabetes. Eunhui Seo, Eun-Kyu Lee, Cheol Soon Lee, Kwang-Hoon Chun, Mi-Young Lee, and Hee-Sook Jun Copyright © 2014 Eunhui Seo et al. All rights reserved. Antioxidant Bioactivity of Samsum Ant (Pachycondyla sennaarensis) Venom Protects against CCL4-Induced Nephrotoxicity in Mice Thu, 03 Apr 2014 12:49:31 +0000 http://www.hindawi.com/journals/omcl/2014/763061/ To assess whether SAV could influence the effects of carbon tetrachloride (CCL4) exposure, mice were treated with SAV in doses of 100, 200, 300 and 400 μg/kg body weight and the effects on oxidative status and kidney function were studied. Serum levels of creatinine, malondialdehyde (MDA), and blood urea, together with renal and hepatic levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified in order to evaluate antioxidant activity. Results showed that the group injected with CCL4 exhibited significantly higher levels of oxidative stress markers, MDA, and significantly lower concentrations of GSH, SOD and catalase. SAV was found to significantly improve these oxidative markers, occasionally, in a dose-dependent manner. Furthermore, treatment with SAV was associated with the same behaviour in respect to kidney functions which had previously been impaired by CCL4. Histopathological examination demonstrated that SAV, in different groups, improved the renal tissue damage induced by CCL4 and histological scores confirmed that significant improvements were obtained after treatment with SAV, particularly with the lowest dose (100 μg/kg body weight). In conclusion, SAV has the potential capability to restore oxidative stability and to improve kidney functions after CCL4 acute injury. Hossam Ebaid, Jameel Al-Tamimi, Iftekhar Hassan, Ibrahim Alhazza, and Mohamed Al-Khalifa Copyright © 2014 Hossam Ebaid et al. All rights reserved. Oxidative Stress-Mediated Reperfusion Injury: Mechanism and Therapies Thu, 03 Apr 2014 08:44:04 +0000 http://www.hindawi.com/journals/omcl/2014/373081/ Zhengyuan Xia, Yanfang Chen, Qian Fan, and Mengzhou Xue Copyright © 2014 Zhengyuan Xia et al. All rights reserved. Oxidative Modification of Proteins in Pediatric Cystic Fibrosis with Bacterial Infections Thu, 03 Apr 2014 06:33:45 +0000 http://www.hindawi.com/journals/omcl/2014/389629/ Pseudomonas aeruginosa and Staphylococcus aureus cause chronic lung infection in cystic fibrosis (CF) patients, inducing chronic oxidative stress. Several markers of plasma protein oxidative damage and glycoxidation and activities of erythrocyte antioxidant enzymes have been compared in stable CF patients chronically infected with Pseudomonas aeruginosa () and Staphylococcus aureus () in relation to healthy subjects (). Concentration of nitric oxide was also measured in the exhaled air from the lower respiratory tract of patients with CF. Elevated glycophore (4.22 ± 0.91 and 4.19 ± 1.04 versus control 3.18 ± 0.53 fluorescence units (FU)/mg protein; ) and carbonyl group levels (1.9 ± 0.64, 1.87 ± 0.45 versus control 0.94 ± 0.19 nmol/mg protein; ) as well as increased glutathione S-transferase activity (2.51 ± 0.88 and 2.57 ± 0.79 U/g Hb versus 0.77 ± 0.16 U/g Hb; ) were noted in Pseudomonas aeruginosa and Staphylococcus aureus infected CF. Kynurenine level (4.91 ± 1.22 versus 3.89 ± 0.54 FU/mg protein; ) was elevated only in Staphylococcus aureus infected CF. These results confirm oxidative stress in CF and demonstrate the usefulness of the glycophore level and protein carbonyl groups as markers of oxidative modifications of plasma proteins in this disease. Izabela Sadowska-Bartosz, Sabina Galiniak, Grzegorz Bartosz, and Marta Rachel Copyright © 2014 Izabela Sadowska-Bartosz et al. All rights reserved. Global Consequences of Liver Ischemia/Reperfusion Injury Tue, 01 Apr 2014 08:06:53 +0000 http://www.hindawi.com/journals/omcl/2014/906965/ Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ’s post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion. Constantinos Nastos, Konstantinos Kalimeris, Nikolaos Papoutsidakis, Marios-Konstantinos Tasoulis, Panagis M. Lykoudis, Kassiani Theodoraki, Despoina Nastou, Vassilios Smyrniotis, and Nikolaos Arkadopoulos Copyright © 2014 Constantinos Nastos et al. All rights reserved. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS Mon, 31 Mar 2014 15:15:07 +0000 http://www.hindawi.com/journals/omcl/2014/212576/ Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans. Arne Trettin, Anke Böhmer, Maria-Theresia Suchy, Irmelin Probst, Ulrich Staerk, Dirk O. Stichtenoth, Jürgen C. Frölich, and Dimitrios Tsikas Copyright © 2014 Arne Trettin et al. All rights reserved. The Effect of tert-Butyl Hydroperoxide-Induced Oxidative Stress on Lean and Steatotic Rat Hepatocytes In Vitro Mon, 31 Mar 2014 14:05:28 +0000 http://www.hindawi.com/journals/omcl/2014/752506/ Oxidative stress and mitochondrial dysfunction play an important role in the pathogenesis of nonalcoholic fatty liver disease and toxic liver injury. The present study was designed to evaluate the effect of exogenous inducer of oxidative stress (tert-butyl hydroperoxide, tBHP) on nonfatty and steatotic hepatocytes isolated from the liver of rats fed by standard and high-fat diet, respectively. In control steatotic hepatocytes, we found higher generation of ROS, increased lipoperoxidation, an altered redox state of glutathione, and decreased ADP-stimulated respiration using NADH-linked substrates, as compared to intact lean hepatocytes. Fatty hepatocytes exposed to tBHP exert more severe damage, lower reduced glutathione to total glutathione ratio, and higher formation of ROS and production of malondialdehyde and are more susceptible to tBHP-induced decrease in mitochondrial membrane potential. Respiratory control ratio of complex I was significantly reduced by tBHP in both lean and steatotic hepatocytes, but reduction in NADH-dependent state 3 respiration was more severe in fatty cells. In summary, our results collectively indicate that steatotic rat hepatocytes occur under conditions of enhanced oxidative stress and are more sensitive to the exogenous source of oxidative injury. This confirms the hypothesis of steatosis being the first hit sensitizing hepatocytes to further damage. Otto Kučera, René Endlicher, Tomáš Roušar, Halka Lotková, Tomáš Garnol, Zdeněk Drahota, and Zuzana Červinková Copyright © 2014 Otto Kučera et al. All rights reserved. Indices of Paraoxonase and Oxidative Status Do Not Enhance the Prediction of Subclinical Cardiovascular Disease in Mixed-Ancestry South Africans Thu, 27 Mar 2014 08:58:10 +0000 http://www.hindawi.com/journals/omcl/2014/135650/ We evaluated the association of indices of paraoxonase (PON1) and oxidative status with subclinical cardiovascular disease (CVD) in mixed-ancestry South Africans. Participants were 491 adults (126 men) who were stratified by diabetes status and body mass index (BMI). Carotid intima-media thickness (CIMT) was used as a measure of subclinical CVD. Indices of PON1 and oxidative status were determined by measuring levels and activities (paraoxonase and arylesterase) of PON1, antioxidant activity (ferric reducing antioxidant power and trolox equivalent antioxidant capacity), and lipid peroxidation markers (malondialdehyde and oxidized LDL). Diabetic subjects (28.9%) displayed a significant decrease in PON1 status and antioxidant activity as well as increase in oxidized LDL and malondialdehyde. A similar profile was apparent across increasing BMI categories. CIMT was higher in diabetic than nondiabetic subjects but showed no variation across BMI categories. Overall, CIMT correlated negatively with indices of antioxidant activity and positively with measures of lipid oxidation. Sex, age, BMI, and diabetes altogether explained 29.2% of CIMT, with no further improvement from adding PON1 and/or antioxidant status indices. Though indices of PON1 and oxidative status correlate with CIMT, their measurements may not be useful for identifying subjects at high CVD risk in this population. M. Macharia, A. P. Kengne, D. M. Blackhurst, R. T. Erasmus, M. Hoffmann, and T. E. Matsha Copyright © 2014 M. Macharia et al. All rights reserved. The Role of Antioxidants in Skin Cancer Prevention and Treatment Wed, 26 Mar 2014 11:21:20 +0000 http://www.hindawi.com/journals/omcl/2014/860479/ Skin cells are constantly exposed to reactive oxygen species (ROS) and oxidative stress from exogenous and endogenous sources. UV radiation is the most important environmental factor in the development of skin cancer and skin aging. The primary products caused by UV exposure are generally direct DNA oxidation or generation of free radicals which form and decompose extremely quickly but can produce effects that can last for hours, days, or even years. UV-induced generation of ROS in the skin develops oxidative stress when their formation exceeds the antioxidant defense ability. The reduction of oxidative stress can be achieved on two levels: by lowering exposure to UVR and/or by increasing levels of antioxidant defense in order to scavenge ROS. The only endogenous protection of our skin is melanin and enzymatic antioxidants. Melanin, the pigment deposited by melanocytes, is the first line of defense against DNA damage at the surface of the skin, but it cannot totally prevent skin damage. A second category of defense is repair processes, which remove the damaged biomolecules before they can accumulate and before their presence results in altered cell metabolism. Additional UV protection includes avoidance of sun exposure, usage of sunscreens, protective clothes, and antioxidant supplements. Aleksandar Godic, Borut Poljšak, Metka Adamic, and Raja Dahmane Copyright © 2014 Aleksandar Godic et al. All rights reserved. Tai Chi Exercise Increases SOD Activity and Total Antioxidant Status in Saliva and Is Linked to an Improvement of Periodontal Disease in the Elderly Wed, 26 Mar 2014 09:46:21 +0000 http://www.hindawi.com/journals/omcl/2014/603853/ The aim of this study was to determine the effect of Tai Chi on biological markers of oxidative stress in saliva and its relationship with periodontal disease (PD) in older adults. We carried out a quasi-experimental study with a sample of 71 sedentary volunteers with PD who were divided into a control group of 34 subjects and an experimental group of 37 subjects who performed Tai Chi 5 days a week for a period of 6 months. PD status was characterized using the Periodontal Disease Index (PDI). Superoxide dismutase (SOD), total antioxidant status (TAS), and TBARS levels of both groups were measured by spectrophotometric methods. In addition, inflammation markers (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were measured by flow cytometry. We found a statistically significant increase in SOD activity () and TAS concentration (), whereas levels of IL-1β were significantly lower (). Likewise, a statistically significant decrease in the PDI () was observed in subjects who performed Tai Chi during a period of 6 months. Our findings suggest that the practice of Tai Chi has both antioxidant and anti-inflammatory effects that are linked to the improvement of PD in older adults. Víctor Manuel Mendoza-Núñez, Beatriz Hernández-Monjaraz, Edelmiro Santiago-Osorio, José Miguel Betancourt-Rule, and Mirna Ruiz-Ramos Copyright © 2014 Víctor Manuel Mendoza-Núñez et al. All rights reserved. Aging Aggravates Nitrate-Mediated ROS/RNS Changes Sun, 23 Mar 2014 11:19:26 +0000 http://www.hindawi.com/journals/omcl/2014/376515/ Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50 μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress included plasma malondialdehyde (MDA), myeloperoxidase (MPO), and reduced glutathione (GSH). Plasma concentrations of NOx and nitrotyrosine served as markers of RNS. Because of the significant differences in basic clinical characters between adults and the elderly, we designed an additional experiment determining ROS/RNS stress in rat cardiac tissue. Additionally, rat thoracic aortic NOS activity served as a marker indicating endothelial function. Our study demonstrated that nitrate therapy significantly increased in vivo ROS/RNS stress in the elderly compared to adult patients, confirmed by animal data. Decreased NOS activity was observed in old rats. Taken together, the present study’s data suggests a synergism between nitrate treatment and the aging process. Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, and Jing Hua Liu Copyright © 2014 Qian Fan et al. All rights reserved. Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer Sun, 23 Mar 2014 08:32:34 +0000 http://www.hindawi.com/journals/omcl/2014/617351/ Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP), which is characterized by colorectal multiple polyps and carcinoma(s). However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC) is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments. Kazuya Shinmura, Masanori Goto, Hong Tao, Hisami Kato, Rie Suzuki, Satoki Nakamura, Tomonari Matsuda, Guang Yin, Makiko Morita, Suminori Kono, and Haruhiko Sugimura Copyright © 2014 Kazuya Shinmura et al. All rights reserved. Resveratrol Oligomers for the Prevention and Treatment of Cancers Sun, 23 Mar 2014 07:04:43 +0000 http://www.hindawi.com/journals/omcl/2014/765832/ Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers. You-Qiu Xue, Jin-Ming Di, Yun Luo, Ke-Jun Cheng, Xing Wei, and Zhi Shi Copyright © 2014 You-Qiu Xue et al. All rights reserved. Redox Status and Aging Link in Neurodegenerative Diseases Thu, 20 Mar 2014 11:43:04 +0000 http://www.hindawi.com/journals/omcl/2014/270291/ Verónica Pérez de la Cruz, Sathyasaikumar V. Korrapati, and José Pedraza-Chaverrí Copyright © 2014 Verónica Pérez de la Cruz et al. All rights reserved. Promoter Hypermethylation and Suppression of Glutathione Peroxidase 3 Are Associated with Inflammatory Breast Carcinogenesis Thu, 20 Mar 2014 11:20:18 +0000 http://www.hindawi.com/journals/omcl/2014/787195/ Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients’ in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients’ clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression. Mona M. Mohamed, Salwa Sabet, Dun-Fa Peng, M. Akram Nouh, Mohamed El-Shinawi, and Wael El-Rifai Copyright © 2014 Mona M. Mohamed et al. All rights reserved. BMP-2 Overexpression Augments Vascular Smooth Muscle Cell Motility by Upregulating Myosin Va via Erk Signaling Thu, 20 Mar 2014 09:21:36 +0000 http://www.hindawi.com/journals/omcl/2014/294150/ Background. The disruption of physiologic vascular smooth muscle cell (VSMC) migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. Methods. VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2). Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca2+ oscillations were recorded. Results. VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca2+ oscillations, generated largely by a “cytosolic oscillator”. Conclusion. BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca2+ oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy. Ming Zhang, Min Yang, Li-ping Liu, Wayne Bond Lau, Hai Gao, Man-kun Xin, Li-Xiao Su, Jian Wang, Shu-Juan Cheng, Qian Fan, and Jing-Hua Liu Copyright © 2014 Ming Zhang et al. All rights reserved. Involvement of miRNAs in Placental Alterations Mediated by Oxidative Stress Tue, 18 Mar 2014 08:08:57 +0000 http://www.hindawi.com/journals/omcl/2014/103068/ Oxidative stress (OS) is known to be strongly involved in a large number of fetal, neonatal, and adult diseases, including placental disorders, leading to pregnancy loss and stillbirths. A growing body of research links OS to preeclampsia, gestational diabetes, obesity, spontaneous abortion, recurrent pregnancy, preterm labor, and intrauterine growth restriction. While a considerable number of miRNAs have been related to physiological functions and pathological conditions of the placenta, a direct link among these miRNAs, placental functions, and OS is still lacking. This review summarizes data describing the role of miRNAs in placental pathophysiological processes and their possible impact on OS damaging responses. As miRNAs can be found in circulation, improving our understanding on their role in the pathogenesis of pregnancy related disorders could have an important impact on the diagnosis and prognosis of these diseases. Alexander Rudov, Walter Balduini, Silvia Carloni, Serafina Perrone, Giuseppe Buonocore, and Maria Cristina Albertini Copyright © 2014 Alexander Rudov et al. All rights reserved. Omega-3 Fatty Acids and Depression: Scientific Evidence and Biological Mechanisms Tue, 18 Mar 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/313570/ The changing of omega-6/omega-3 polyunsaturated fatty acids (PUFA) in the food supply of Western societies occurred over the last 150 years is thought to promote the pathogenesis of many inflammatory-related diseases, including depressive disorders. Several epidemiological studies reported a significant inverse correlation between intake of oily fish and depression or bipolar disorders. Studies conducted specifically on the association between omega-3 intake and depression reported contrasting results, suggesting that the preventive role of omega-3 PUFA may depend also on other factors, such as overall diet quality and the social environment. Accordingly, tertiary prevention with omega-3 PUFA supplement in depressed patients has reached greater effectiveness during the last recent years, although definitive statements on their use in depression therapy cannot be yet freely asserted. Among the biological properties of omega-3 PUFA, their anti-inflammatory effects and their important role on the structural changing of the brain should be taken into account to better understand the possible pathway through which they can be effective both in preventing or treating depression. However, the problem of how to correct the inadequate supply of omega-3 PUFA in the Westernized countries’ diet is a priority in order to set food and health policies and also dietary recommendations for individuals and population groups. Giuseppe Grosso, Fabio Galvano, Stefano Marventano, Michele Malaguarnera, Claudio Bucolo, Filippo Drago, and Filippo Caraci Copyright © 2014 Giuseppe Grosso et al. All rights reserved.