Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Dual Stimulus-Dependent Effect of Oenothera paradoxa Extract on the Respiratory Burst in Human Leukocytes: Suppressing for Escherichia coli and Phorbol Myristate Acetate and Stimulating for Formyl-Methionyl-Leucyl-Phenylalanine Sun, 14 Sep 2014 09:00:29 +0000 http://www.hindawi.com/journals/omcl/2014/764367/ Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans. Izabela Burzynska-Pedziwiatr, Malgorzata Bukowiecka-Matusiak, Marzena Wojcik, Waldemar Machala, Malgorzata Bienkiewicz, Grzegorz Spolnik, Witold Danikiewicz, and Lucyna Alicja Wozniak Copyright © 2014 Izabela Burzynska-Pedziwiatr et al. All rights reserved. Lipid Peroxidation Products in Human Health and Disease 2014 Sun, 14 Sep 2014 06:07:03 +0000 http://www.hindawi.com/journals/omcl/2014/162414/ Kota V. Ramana, Sanjay Srivastava, and Sharad S. Singhal Copyright © 2014 Kota V. Ramana et al. All rights reserved. Withania coagulans Fruit Extract Reduces Oxidative Stress and Inflammation in Kidneys of Streptozotocin-Induced Diabetic Rats Sun, 14 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/201436/ The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat’s kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1β, IL-6, and TNF-α) and immunoregulatory cytokines (IL-4 and IFN-γ) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10 mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies. Shreesh Ojha, Juma Alkaabi, Naheed Amir, Azimullah Sheikh, Ahmad Agil, Mohamed Abdelmonem Fahim, and Abdu Adem Copyright © 2014 Shreesh Ojha et al. All rights reserved. Effect of the French Oak Wood Extract Robuvit on Markers of Oxidative Stress and Activity of Antioxidant Enzymes in Healthy Volunteers: A Pilot Study Sun, 31 Aug 2014 08:09:47 +0000 http://www.hindawi.com/journals/omcl/2014/639868/ We examined in vitro antioxidant capacity of polyphenolic extract obtained from the wood of oak Quercus robur (QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found an in vitro antioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasma in vivo. Martina Horvathova, Zuzana Orszaghova, Lucia Laubertova, Magdalena Vavakova, Peter Sabaka, Peter Rohdewald, Zdenka Durackova, and Jana Muchova Copyright © 2014 Martina Horvathova et al. All rights reserved. Effect of the Antihypertensive Drug Enalapril on Oxidative Stress Markers and Antioxidant Enzymes in Kidney of Spontaneously Hypertensive Rat Thu, 28 Aug 2014 13:00:40 +0000 http://www.hindawi.com/journals/omcl/2014/608512/ Oxidative stress has been suggested to play a role in hypertension and hypertension induced organ damage. This study examined the effect of enalapril, an antihypertensive drug, on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat (SHR) and Nω -nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups (SHR, SHR+enalapril, SHR+L-NAME, and SHR+enalapril+L-NAME). Enalapril (30 mg kg−1 day−1) was administered from week 4 to week 28 and L-NAME (25 mg kg−1 day−1) was administered from week 16 to week 28 in drinking water. Systolic blood pressure (SBP) was measured during the experimental period. At the end of experimental periods, rats were sacrificed; urine, blood, and kidneys were collected for the assessment of creatinine clearance, total protein, total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and catalase (CAT), as well as histopathological examination. Enalapril treatment significantly enhanced the renal TAS level () and SOD activity (), reduced the TBARS levels (), and also prevented the renal dysfunction and histopathological changes. The results indicate that, besides its hypotensive and renoprotective effects, enalapril treatment also diminishes oxidative stress in the kidneys of both the SHR and SHR+L-NAME groups. G. Chandran, K. N. S. Sirajudeen, Nik Syamimi Nik Yusoff, M. Swamy, and Mutum S. Samarendra Copyright © 2014 G. Chandran et al. All rights reserved. Positive Relationship between Total Antioxidant Status and Chemokines Observed in Adults Thu, 28 Aug 2014 12:08:43 +0000 http://www.hindawi.com/journals/omcl/2014/693680/ Objective. Human evidence is limited regarding the interaction between oxidative stress biomarkers and chemokines, especially in a population of adults without overt clinical disease. The current study aims to examine the possible relationships of antioxidant and lipid peroxidation markers with several chemokines in adults. Methods. We assessed cross-sectional associations of total antioxidant status (TAS) and two lipid peroxidation markers malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) with a suite of serum chemokines, including CXCL-1 (GRO-), CXCL-8 (IL-8), CXCL-10 (IP-10), CCL-2 (MCP-1), CCL-5 (RANTES), CCL-8 (MCP-2), CCL-11 (Eotaxin-1), and CCL-17 (TARC), among 104 Chinese adults without serious preexisting clinical conditions in Beijing before 2008 Olympics. Results. TAS showed significantly positive correlations with MCP-1 (, ), MCP-2 (, ), Eotaxin-1 (, ), and TARC (, ). The positive correlations remained unchanged after controlling for age, sex, body mass index, smoking, and alcohol drinking status. No associations were found between any of the chemokines measured in this study and MDA or TBARS. Similar patterns were observed when the analyses were limited to nonsmokers. Conclusion. Total antioxidant status is positively associated with several chemokines in this adult population. Yanli Li, Richard W. Browne, Matthew R. Bonner, Furong Deng, Lili Tian, and Lina Mu Copyright © 2014 Yanli Li et al. All rights reserved. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats Wed, 27 Aug 2014 06:17:33 +0000 http://www.hindawi.com/journals/omcl/2014/961326/ Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes. Abraham Said Arellano-Buendía, Fernando Enrique García-Arroyo, Magdalena Cristóbal-García, María Lilia Loredo-Mendoza, Edilia Tapia-Rodríguez, Laura Gabriela Sánchez-Lozada, and Horacio Osorio-Alonso Copyright © 2014 Abraham Said Arellano-Buendía et al. All rights reserved. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes Wed, 27 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/654198/ Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. Quan He, Nicole Harris, Jun Ren, and Xianlin Han Copyright © 2014 Quan He et al. All rights reserved. Human AP Endonuclease 1: A Potential Marker for the Prediction of Environmental Carcinogenesis Risk Tue, 26 Aug 2014 06:22:02 +0000 http://www.hindawi.com/journals/omcl/2014/730301/ Human apurinic/apyrimidinic endonuclease 1 (APE1) functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individual’s genetic make-up with environmental factors (gene-environment interaction) is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke) and physical carcinogens (ultraviolet and ionizing radiation) is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk. Jae Sung Park, Hye Lim Kim, Yeo Jin Kim, Jong-Il Weon, Mi-Kyung Sung, Hai Won Chung, and Young Rok Seo Copyright © 2014 Jae Sung Park et al. All rights reserved. Diabetes and the Brain: Oxidative Stress, Inflammation, and Autophagy Sun, 24 Aug 2014 11:09:27 +0000 http://www.hindawi.com/journals/omcl/2014/102158/ Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB), a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation. María Muriach, Miguel Flores-Bellver, Francisco J. Romero, and Jorge M. Barcia Copyright © 2014 María Muriach et al. All rights reserved. Cardioprotection against Ischemia/Reperfusion by Licochalcone B in Isolated Rat Hearts Thu, 21 Aug 2014 08:42:14 +0000 http://www.hindawi.com/journals/omcl/2014/134862/ The generation of reactive oxygen species (ROS) is a major cause of heart injury induced by ischemia-reperfusion. The left ventricular developed pressure (LVDP) and the maximum up/down rate of left ventricular pressure () were documented by a physiological recorder. Myocardial infarct size was estimated macroscopically using 2,3,5-triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. The levels of C-reactive protein (CRP), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were analyzed to determine the inflammation status of the myocardial tissue. Cardiomyocyte apoptosis analysis was performed using the In Situ Cell Death Detection Kit, POD. Accordingly, licochalcone B pretreatment improved the heart rate (HR), increased LVDP, and decreased CK and LDH levels in coronary flow. SOD level and GSH/GSSG ratio increased, whereas the levels of MDA, TNF-α, and CRP and activities of IL-8 and IL-6 decreased in licochalcone B-treated groups. The infarct size and cell apoptosis in hearts from licochalcone B-treated group were lower than those in hearts from the I/R control group. Therefore, the cardioprotective effects of licochalcone B may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities. Jichun Han, Dong Wang, Bacui Yu, Yanming Wang, Huanhuan Ren, Bo Zhang, Yonghua Wang, and Qiusheng Zheng Copyright © 2014 Jichun Han et al. All rights reserved. The Protective Effects of Curcumin on Experimental Acute Liver Lesion Induced by Intestinal Ischemia-Reperfusion through Inhibiting the Pathway of NF-κB in a Rat Model Wed, 20 Aug 2014 08:33:22 +0000 http://www.hindawi.com/journals/omcl/2014/191624/ Objective. In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R), which induces an acute liver lesion. Methods. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline) was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) expression. Conclusion. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway. Zhe Fan, Huirong Jing, Jihong Yao, Yang Li, Xiaowei Hu, Huizhu Shao, Gang Shen, Jiyong Pan, Fuwen Luo, and Xiaofeng Tian Copyright © 2014 Zhe Fan et al. All rights reserved. Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy Wed, 20 Aug 2014 07:35:33 +0000 http://www.hindawi.com/journals/omcl/2014/780179/ Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid β peptide (Aβ), an important component in Alzheimer’s disease (AD) pathogenesis, and Aβ can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβ import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP) formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed. Pasquale Picone, Domenico Nuzzo, Luca Caruana, Valeria Scafidi, and Marta Di Carlo Copyright © 2014 Pasquale Picone et al. All rights reserved. Oxidative Stress-Mediated Aging during the Fetal and Perinatal Periods Mon, 18 Aug 2014 12:06:41 +0000 http://www.hindawi.com/journals/omcl/2014/358375/ Oxidative stress is worldwide recognized as a fundamental component of the aging, a process that begins before birth. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress is caused by an imbalance between the production of free radicals and the ability of antioxidant system to detoxify them. Oxidative stress can occur early in pregnancy and continue in the postnatal period; this damage is implicated in the pathophysiology of pregnancy-related disorders, including recurrent pregnancy loss, preeclampsia and preterm premature rupture of membranes. Moreover, diseases of the neonatal period such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia are related to free radical damage. The specific contribution of oxidative stress to the pathogenesis and progression of these neonatal diseases is only partially understood. This review summarizes what is known about the role of oxidative stress in pregnancy and in the pathogenesis of common disorders of the newborn, as a component of the early aging process. Lucia Marseglia, Gabriella D’Angelo, Sara Manti, Teresa Arrigo, Ignazio Barberi, Russel J. Reiter, and Eloisa Gitto Copyright © 2014 Lucia Marseglia et al. All rights reserved. Effect of Staurosporine in the Morphology and Viability of Cerebellar Astrocytes: Role of Reactive Oxygen Species and NADPH Oxidase Sun, 17 Aug 2014 11:08:36 +0000 http://www.hindawi.com/journals/omcl/2014/678371/ Cell death implies morphological changes that may contribute to the progression of this process. In astrocytes, the mechanisms involving the cytoskeletal changes during cell death are not well explored. Although NADPH oxidase (NOX) has been described as being a critical factor in the production of ROS, not much information is available about the participation of NOX-derived ROS in the cell death of astrocytes and their role in the alterations of the cytoskeleton during the death of astrocytes. In this study, we have evaluated the participation of ROS in the death of cultured cerebellar astrocytes using staurosporine (St) as death inductor. We found that astrocytes express NOX1, NOX2, and NOX4. Also, St induced an early ROS production and NOX activation that participate in the death of astrocytes. These findings suggest that ROS produced by St is generated through NOX1 and NOX4. Finally, we showed that the reorganization of tubulin and actin induced by St is ROS independent and that St did not change the level of expression of these cytoskeletal proteins. We conclude that ROS produced by a NOX is required for cell death in astrocytes, but not for the morphological alterations induced by St. Mauricio Olguín-Albuerne, Guadalupe Domínguez, and Julio Morán Copyright © 2014 Mauricio Olguín-Albuerne et al. All rights reserved. Short-Term Diet and Moderate Exercise in Young Overweight Men Modulate Cardiocyte and Hepatocarcinoma Survival by Oxidative Stress Wed, 13 Aug 2014 10:53:11 +0000 http://www.hindawi.com/journals/omcl/2014/131024/ The present study was designed to evaluate the effects of diet lifestyle on extending lifespan and reducing liver cancer risk. Young overweight men , without metabolic syndrome, were placed in a 3-week residential program on a low-fat diet and moderate aerobic exercise. In each subject, pre- and postintervention fasting blood were collected for evaluating levels of serum lipids, and oxidative stress markers. Using subject sera and cardiomyocyte (H9C2) culture systems, we measured heat shock protein 27 and 90 expression, lipid accumulation, and oxidative stress marker levels. After 3-weeks of diet, significant reductions in body mass index, serum lipids and lipid ratios, and oxidative markers were recorded. In vitro, we observed that the addition of postintervention sera increased H9C2 cell number and reduced HSP27 and 90 expression, mitochondrial superoxide anion, and lipid accumulation with a parallel increase in nitric oxide (NO) production (all ). At the same time, postintervention sera decreased human liver hepatocellular carcinoma cell line (HepG-2) proliferation, lipid accumulation, oxidative stress, and extracellular-signal-regulated kinases (ERK1/2) activity. Lifestyle modification in young overweight men, without metabolic syndrome, could ameliorate cardiocyte survival and reduce hepatocellular carcinoma cell proliferation. Marcellino Monda, Giovanni Messina, Ilaria Scognamiglio, Angela Lombardi, Giuseppe A. Martin, Pasquale Sperlongano, Marina Porcelli, Michele Caraglia, and Paola Stiuso Copyright © 2014 Marcellino Monda et al. All rights reserved. Anticonvulsant and Antioxidant Effects of Tilia americana var. mexicana and Flavonoids Constituents in the Pentylenetetrazole-Induced Seizures Wed, 13 Aug 2014 05:11:47 +0000 http://www.hindawi.com/journals/omcl/2014/329172/ Tilia genus is commonly used around the world for its central nervous system properties; it is prepared as tea and used as tranquilizing, anticonvulsant, and analgesic. In this study, anticonvulsant activity of the Tilia americana var. mexicana inflorescences and leaves was investigated by evaluating organic and aqueous extracts (100, 300, and 600 mg/kg, i.p.) and some flavonoids in the pentylenetetrazole-induced seizures in mice. Moreover, antioxidant effect of these extracts and flavonoids was examined in an in vitro study by using spectrophotometric technique. Significant activity was observed in the methanol extract from inflorescences. An HPLC analysis of the methanol extract from inflorescences and leaves of Tilia allowed demonstrating the respective presence of some partial responsible flavonoid constituents: quercetin (20.09 ± 1.20 μg/mg and 3.39 ± 0.10 μg/mg), rutin (3.52 ± 0.21 μg/mg and 8.94 ± 0.45 μg/mg), and isoquercitrin (1.74 ± 0.01 μg/mg and 1.24 ± 0.13 μg/mg). In addition, significant but different antioxidant properties were obtained among the flavonoids and the extracts investigated. Our results provide evidence of the anticonvulsant activity of Tilia reinforcing its utility for central nervous system diseases whose mechanism of action might involve partial antioxidant effects due to the presence of flavonoids. Noemí Cárdenas-Rodríguez, María Eva González-Trujano, Eva Aguirre-Hernández, Matilde Ruíz-García, Aristides Sampieri III, Elvia Coballase-Urrutia, and Liliana Carmona-Aparicio Copyright © 2014 Noemí Cárdenas-Rodríguez et al. All rights reserved. Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation Tue, 12 Aug 2014 11:44:59 +0000 http://www.hindawi.com/journals/omcl/2014/302528/ The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis () treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score). Lenka Borska, Ctirad Andrys, Jan Krejsek, Vladimir Palicka, Marcela Chmelarova, Kvetoslava Hamakova, Jan Kremlacek, and Zdenek Fiala Copyright © 2014 Lenka Borska et al. All rights reserved. Propofol Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-Alpha Expression and Myocardial Depression through Decreasing the Generation of Superoxide Anion in Cardiomyocytes Mon, 11 Aug 2014 11:21:31 +0000 http://www.hindawi.com/journals/omcl/2014/157376/ TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis. Jing Tang, Ji-Jie Hu, Chun-Hua Lu, Jia-Ni Liang, Jin-Fang Xiao, You-Tan Liu, Chun-Shui Lin, and Zai-Sheng Qin Copyright © 2014 Jing Tang et al. All rights reserved. Oxidative Stress: Implications for the Development of Diabetic Retinopathy and Antioxidant Therapeutic Perspectives Sun, 10 Aug 2014 12:11:17 +0000 http://www.hindawi.com/journals/omcl/2014/752387/ In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR. Ying Wu, Luosheng Tang, and Baihua Chen Copyright © 2014 Ying Wu et al. All rights reserved. Monoterpenoid Terpinen-4-ol Exhibits Anticonvulsant Activity in Behavioural and Electrophysiological Studies Sun, 10 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/703848/ Terpinen-4-ol (4TRP) is a monoterpenoid alcoholic component of essential oils obtained from several aromatic plants. We investigated the psychopharmacological and electrophysiological activities of 4TRP in male Swiss mice and Wistar rats. 4TRP was administered intraperitoneally (i.p.) at doses of 25 to 200 mg/kg and intracerebroventricularly (i.c.v.) at concentrations of 10, 20, and 40 ng/2 μL. For in vitro experiments, 4TRP concentrations were 0.1 mM and 1.0 mM. 4TRP (i.p.) inhibited pentylenetetrazol- (PTZ-) induced seizures, indicating anticonvulsant effects. Electroencephalographic recordings showed that 4TRP (i.c.v.) protected against PTZ-induced seizures, corroborating the behavioural results. To determine whether 4TRP exerts anticonvulsant effects via regulation of GABAergic neurotransmission, we measured convulsions induced by 3-mercapto-propionic acid (3-MP). The obtained results showed involvement of the GABAergic system in the anticonvulsant action exerted by 4TRP, but flumazenil, a selective antagonist of the benzodiazepine site of the receptor, did not reverse the anticonvulsant effect, demonstrating that 4TRP does not bind to the benzodiazepine-binding site. Furthermore, 4TRP decreased the sodium current through voltage-dependent sodium channels, and thus its anticonvulsant effect may be related to changes in neuronal excitability because of modulation of these channels. Franklin F. F. Nóbrega, Mirian G. S. S. Salvadori, Cintia J. Masson, Carlos F. Mello, Tiago S. Nascimento, José H. Leal-Cardoso, Damião P. de Sousa, and Reinaldo N. Almeida Copyright © 2014 Franklin F. F. Nóbrega et al. All rights reserved. Epicatechin and Catechin Modulate Endothelial Activation Induced by Platelets of Patients with Peripheral Artery Disease Thu, 07 Aug 2014 07:18:16 +0000 http://www.hindawi.com/journals/omcl/2014/691015/ Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that epicatechin plus catechin reduces endothelial activation induced by activated platelets. R. Carnevale, L. Loffredo, C. Nocella, S. Bartimoccia, T. Bucci, E. De Falco, M. Peruzzi, I. Chimenti, G. Biondi-Zoccai, P. Pignatelli, F. Violi, and G. Frati Copyright © 2014 R. Carnevale et al. All rights reserved. The Effects of Sesquiterpenes-Rich Extract of Alpinia oxyphylla Miq. on Amyloid-β-Induced Cognitive Impairment and Neuronal Abnormalities in the Cortex and Hippocampus of Mice Thu, 07 Aug 2014 06:57:10 +0000 http://www.hindawi.com/journals/omcl/2014/451802/ As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ1−42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions. Shao-Huai Shi, Xu Zhao, Bing Liu, Huan Li, Ai-Jing Liu, Bo Wu, Kai-Shun Bi, and Ying Jia Copyright © 2014 Shao-Huai Shi et al. All rights reserved. Deletion of Metallothionein Exacerbates Intermittent Hypoxia-Induced Oxidative and Inflammatory Injury in Aorta Wed, 06 Aug 2014 07:27:52 +0000 http://www.hindawi.com/journals/omcl/2014/141053/ The present study was to explore the effect of metallothionein (MT) on intermittent hypoxia (IH) induced aortic pathogenic changes. Markers of oxidative damages, inflammation, and vascular remodeling were observed by immunohistochemical staining after 3 days and 1, 3, and 8 weeks after IH exposures. Endogenous MT was induced after 3 days of IH but was significantly decreased after 8 weeks of IH. Compared with the wild-type mice, MT knock-out mice exhibited earlier and more severe pathogenic changes of oxidative damages, inflammatory responses, and cellular apoptosis, as indicated by the significant accumulation of collagen, increased levels of connective tissue growth factor, transforming growth factor , tumor necrosis factor-alpha, vascular cell adhesion molecule 1,3-nitrotyrosine, and 4-hydroxy-2-nonenal in the aorta. These findings suggested that chronic IH may lead to aortic damages characterized by oxidative stress and inflammation, and MT may play a pivotal role in the above pathogenesis process. Shanshan Zhou, Yonggang Wang, Yi Tan, Xiaohong Cai, Lu Cai, Jun Cai, and Yang Zheng Copyright © 2014 Shanshan Zhou et al. All rights reserved. Nitric Oxide-Related Oxidative Stress and Redox Status in Health and Disease Wed, 23 Jul 2014 10:13:00 +0000 http://www.hindawi.com/journals/omcl/2014/129651/ Darko Modun, Daniela Giustarini, and Dimitrios Tsikas Copyright © 2014 Darko Modun et al. All rights reserved. Subanesthetic Isoflurane Reduces Zymosan-Induced Inflammation in Murine Kupffer Cells by Inhibiting ROS-Activated p38 MAPK/NF-κB Signaling Wed, 23 Jul 2014 07:28:44 +0000 http://www.hindawi.com/journals/omcl/2014/851692/ Volatile anesthetic isoflurane (ISO) has immunomodulatory effects. The fungal component zymosan (ZY) induces inflammation through toll-like receptor 2 or dectin-1 signaling. We investigated the molecular actions of subanesthetic (0.7%) ISO against ZY-induced inflammatory activation in murine Kupffer cells (KCs), which are known as the resident macrophages within the liver. We observed that ISO reduced ZY-induced cyclooxygenase 2 upregulation and prostaglandin E2 release, as determined by western blot and radioimmunoassay, respectively. ISO also reduced the production of tumor necrosis factor-α, interleukin-1β, IL-6, high-mobility group box-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 as assessed by enzyme-linked immunosorbent assays. ISO blocked the ZY-induced nuclear translocation and DNA-binding activity of nuclear factor- (NF)-κB p65. Moreover, ISO attenuated ZY-induced p38 mitogen-activated protein kinase (MAPK) activation partly by scavenging reactive oxygen species (ROS); the interregulation that ROS activated p38 MAPK followed by NF-κB activation was crucial for the ZY-induced inflammatory responses in KCs. An in vivo study by peritoneal injection of ZY into BALB/C mice confirmed the anti-inflammatory properties of 0.7% ISO against ZY in KCs. These results suggest that ISO ameliorates ZY-induced inflammatory responses in murine KCs by inhibiting the interconnected ROS/p38 MAPK/NF-κB signaling pathways. Hui Wang, Lei Wang, Nan-lin Li, Jun-tang Li, Feng Yu, Ya-li Zhao, Ling Wang, Jun Yi, Ling Wang, Jie-fang Bian, Jiang-hao Chen, Shi-fang Yuan, Ting Wang, Yong-gang Lv, Ning-ning Liu, Xiao-shan Zhu, Rui Ling, and Jun Yun Copyright © 2014 Hui Wang et al. All rights reserved. Decitabine and SAHA-Induced Apoptosis Is Accompanied by Survivin Downregulation and Potentiated by ATRA in p53-Deficient Cells Mon, 21 Jul 2014 11:19:42 +0000 http://www.hindawi.com/journals/omcl/2014/165303/ While p53-dependent apoptosis is triggered by combination of methyltransferase inhibitor decitabine (DAC) and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in leukemic cell line CML-T1, reactive oxygen species (ROS) generation as well as survivin and Bcl-2 deregulation participated in DAC + SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of survivin expression level is accompanied by its delocalization from centromere-related position in mitotic cells suggesting that both antiapoptotic and cell cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of subtoxic concentration of all-trans-retinoic acid (ATRA) increases the efficiency of DAC + SAHA combination on viability, apoptosis induction, and ROS generation in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA combination. Therefore, combination of ATRA with DAC and SAHA represents promising tool for therapy of leukemic disease with nonfunctional p53 signalization. Barbora Brodská, Petra Otevřelová, and Aleš Holoubek Copyright © 2014 Barbora Brodská et al. All rights reserved. The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution Sun, 20 Jul 2014 07:30:20 +0000 http://www.hindawi.com/journals/omcl/2014/671539/ Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example, -carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants. Borut Poljšak and Rok Fink Copyright © 2014 Borut Poljšak and Rok Fink. All rights reserved. Oxidative Stress and Metabolic Pathologies: From an Adipocentric Point of View Sun, 20 Jul 2014 06:10:03 +0000 http://www.hindawi.com/journals/omcl/2014/908539/ Oxidative stress plays a pathological role in the development of various diseases including diabetes, atherosclerosis, or cancer. Systemic oxidative stress results from an imbalance between oxidants derivatives production and antioxidants defenses. Reactive oxygen species (ROS) are generally considered to be detrimental for health. However, evidences have been provided that they can act as second messengers in adaptative responses to stress. Obesity represents a major risk factor for deleterious associated pathologies such as type 2 diabetes, liver, and coronary heart diseases. Many evidences regarding obesity-induced oxidative stress accumulated over the past few years based on established correlations of biomarkers or end-products of free-radical-mediated oxidative stress with body mass index. The hypothesis that oxidative stress plays a significant role in the development of metabolic disorders, especially insulin-resistance state, is supported by several studies where treatments reducing ROS production reverse metabolic alterations, notably through improvement of insulin sensitivity, hyperlipidemia, or hepatic steatosis. In this review, we will develop the mechanistic links between oxidative stress generated by adipose tissue in the context of obesity and its impact on metabolic complications development. We will also attempt to discuss potential therapeutic approaches targeting obesity-associated oxidative stress in order to prevent associated-metabolic complications. Soazig Le Lay, Gilles Simard, Maria Carmen Martinez, and Ramaroson Andriantsitohaina Copyright © 2014 Soazig Le Lay et al. All rights reserved. A Review on Hemeoxygenase-2: Focus on Cellular Protection and Oxygen Response Thu, 17 Jul 2014 12:27:26 +0000 http://www.hindawi.com/journals/omcl/2014/604981/ Hemeoxygenase (HO) system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia. Jorge Muñoz-Sánchez and María Elena Chánez-Cárdenas Copyright © 2014 Jorge Muñoz-Sánchez and María Elena Chánez-Cárdenas. All rights reserved.