Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Antioxidant Capacity of “Mexican Arnica” Heterotheca inuloides Cass Natural Products and Some Derivatives: Their Anti-Inflammatory Evaluation and Effect on C. elegans Life Span Mon, 02 Mar 2015 10:03:08 +0000 http://www.hindawi.com/journals/omcl/2015/843237/ It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as 1O2, , H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm. José Luis Rodríguez-Chávez, Elvia Coballase-Urrutia, Antonio Nieto-Camacho, and Guillermo Delgado-Lamas Copyright © 2015 José Luis Rodríguez-Chávez et al. All rights reserved. P2X7 Receptor as a Key Player in Oxidative Stress-Driven Cell Fate in Nonalcoholic Steatohepatitis Sun, 01 Mar 2015 12:36:56 +0000 http://www.hindawi.com/journals/omcl/2015/172493/ Incidences of nonalcoholic fatty liver disease parallels increase in the global obesity epidemic. NAFLD has been shown to be associated with risks of cardiometabolic disorders and kidney disturbances. It is accompanied by insulin and leptin resistance that complicate the diagnosis and treatment of this public health menace. Though significant research is underway for understanding the molecular mechanisms of NAFLD and its subsequent inflammatory and fibrotic manifestations like nonalcoholic steatohepatitis, the role of purinergic receptors has been unclear. It is increasingly being recognized that damage associated molecular patterns like NAD and ATP that are released from injured cells via hepatocellular injury either by oxidative stress or lipotoxicity from steatosis activate the purinergic receptor. Based on evidence from inflammatory responses in the airways and vasculature and autoimmune complications in humans and rodents, it is beyond doubt that hepatocellular inflammation such as that seen in NASH can result from the activation of purinergic receptors. This event can result in the formation of inflammasomes and can be an important pathway for the progression of NASH. The present review evaluates the current knowledge of the role of oxidative stress and its signaling via P2X7 receptors in hepatocellular injury that might contribute to the NASH pathophysiology. Saurabh Chatterjee and Suvarthi Das Copyright © 2015 Saurabh Chatterjee and Suvarthi Das. All rights reserved. Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds Sun, 01 Mar 2015 09:05:18 +0000 http://www.hindawi.com/journals/omcl/2015/343706/ Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury. Yasuhiro Ishihara, Takuya Takemoto, Atsuhiko Ishida, and Takeshi Yamazaki Copyright © 2015 Yasuhiro Ishihara et al. All rights reserved. Association of Age-Related Macular Degeneration with Erythrocyte Antioxidant Enzymes Activity and Serum Total Antioxidant Status Sat, 28 Feb 2015 12:46:07 +0000 http://www.hindawi.com/journals/omcl/2015/804054/ The aim was to estimate association of the oxidative stress with the occurrence of age-related macular degeneration (AMD). The activities of erythrocyte antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and additionally serum total antioxidant status (TAS) were used as indicators of the oxidative stress level. 57 AMD patients (32 early and 25 late AMD) and 50 healthy, age and gender matched controls were included. GPx activity () and serum TAS () were significantly lower in AMD patients. The difference was not significant for SOD or CAT activities. Significant interaction between GPx and SOD was detected (). At high levels of SOD activity (over 75th percentile), one standard deviation decrease in GPx increases the odds for AMD for six times (OR = 6.22; ). ROC analysis revealed that combined values of GPx activity and TAS are significant determinants of AMD status. Accuracy, sensitivity, specificity, and positive and negative predictive values were 75%, 95%, 52%, 69%, and 90%, respectively. The study showed that low GPx activity and TAS are associated with AMD. SOD modulates the association of GPx and AMD. The results suggest that erythrocyte antioxidant enzymes activity and serum TAS could be promising markers for the prediction of AMD. Ivna Plestina-Borjan, Damir Katusic, Maria Medvidovic-Grubisic, Daniela Supe-Domic, Kajo Bucan, Leida Tandara, and Veljko Rogosic Copyright © 2015 Ivna Plestina-Borjan et al. All rights reserved. Diabetes and Alzheimer Disease, Two Overlapping Pathologies with the Same Background: Oxidative Stress Thu, 26 Feb 2015 08:53:26 +0000 http://www.hindawi.com/journals/omcl/2015/985845/ There are several oxidative stress-related pathways interconnecting Alzheimer’s disease and type II diabetes, two public health problems worldwide. Coincidences are so compelling that it is attractive to speculate they are the same disorder. However, some pathological mechanisms as observed in diabetes are not necessarily the same mechanisms related to Alzheimer’s or the only ones related to Alzheimer’s pathology. Oxidative stress is inherent to Alzheimer’s and feeds a vicious cycle with other key pathological features, such as inflammation and Ca2+ dysregulation. Alzheimer’s pathology by itself may lead to insulin resistance in brain, insulin resistance being an intervening variable in the neurodegenerative disorder. Hyperglycemia and insulin resistance from diabetes, overlapping with the Alzheimer’s pathology, aggravate the progression of the neurodegenerative processes, indeed. But the same pathophysiological background is behind the consequences, oxidative stress. We emphasize oxidative stress and its detrimental role in some key regulatory enzymes. Sergio Rosales-Corral, Dun-Xian Tan, Lucien Manchester, and Russel J. Reiter Copyright © 2015 Sergio Rosales-Corral et al. All rights reserved. Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a Thu, 26 Feb 2015 06:29:02 +0000 http://www.hindawi.com/journals/omcl/2015/792846/ Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients’ pulmonary function. We also studied the expression profile of circulating messenger RNA (mRNAs) and found that miR23a controlled 17% of the significantly changed mRNA, including PGC1α, which was recently associated with the progression of IPAH. Finally we found that silencing of miR23a resulted in an increase of the expression of PGC1α, as well as in its well-known regulated genes CYC, SOD, NRF2, and HO1. The results point to the utility of circulating miRNA expression as a biomarker of disease progression. Irene Sarrion, Lara Milian, G. Juan, Mercedes Ramon, Idelfonso Furest, Carmen Carda, Julio Cortijo Gimeno, and Manuel Mata Roig Copyright © 2015 Irene Sarrion et al. All rights reserved. Protective Effects of the Flavonoid Chrysin against Methylmercury-Induced Genotoxicity and Alterations of Antioxidant Status, In Vivo Tue, 24 Feb 2015 16:30:32 +0000 http://www.hindawi.com/journals/omcl/2015/602360/ The use of phytochemicals has been widely used as inexpensive approach for prevention of diseases related to oxidative damage due to its antioxidant properties. One of dietary flavonoids is chrysin (CR), found mainly in passion fruit, honey, and propolis. Methylmercury (MeHg) is a toxic metal whose main toxic mechanism is oxidative damage. Thus, the study aimed to evaluate the antioxidant effects of CR against oxidative damage induced by MeHg in Wistar rats. Animals were treated with MeHg (30 µg/kg/bw) in presence and absence of CR (0.10, 1.0, and 10 mg/kg/bw) by gavage for 45 days. Glutathione (GSH) in blood was quantified spectrophotometrically and for monitoring of DNA damage, comet assay was used in leukocytes and hepatocytes. MeHg led to a significant increase in the formation of comets; when the animals were exposed to the metal in the presence of CR, higher concentrations of CR showed protective effects. Moreover, exposure to MeHg decreased the levels of GSH and GSH levels were restored in the animals that received CR plus MeHg. Taken together the findings of the present work indicate that consumption of flavonoids such as CR may protect humans against the adverse health effects caused by MeHg. Eduardo Scandinari Manzolli, Juliana Mara Serpeloni, Denise Grotto, Jairo Kennup Bastos, Lusânia Maria Greggi Antunes, Fernando Barbosa Jr., and Gustavo Rafael Mazzaron Barcelos Copyright © 2015 Eduardo Scandinari Manzolli et al. All rights reserved. The Loss of Cellular Junctions in Epithelial Lung Cells Induced by Cigarette Smoke Is Attenuated by Corilagin Tue, 24 Feb 2015 11:45:16 +0000 http://www.hindawi.com/journals/omcl/2015/631758/ Cigarette smoke (CS) contains over 4700 compounds, many of which can affect cellular redox balance through free radicals production or through the modulation of antioxidant enzymes. The respiratory tract is one of the organs directly exposed to CS and it is known that CS can damage the integrity of lung epithelium by affecting cell junctions and increasing epithelium permeability. In this study, we have used a human lung epithelial cell line, Calu-3, to evaluate the effect of CS on lung epithelial cell junctions levels, with special focus on the expression of two proteins involved in intercellular communication: connexins (Cx) 40 and 43. CS exposure increased Cx40 gene expression but not of Cx43. CS also induced NFκB activation and the formation of 4HNE-Cxs adducts. Since corilagin, a natural polyphenol, is able to inhibit NFκB activation, we have determined whether corilagin could counteract the effect of CS on Cxs expression. Corilagin was able to diminish CS induced Cx40 gene expression, 4HNE-Cx40 adducts formation, and NFκB activation. The results of this study demonstrated that CS induced the loss of cellular junctions in lung epithelium, possibly as a consequence of Cx-4HNE adducts formation, and corilagin seems to be able to abolish these CS induced alterations. Ximena M. Muresan, Franco Cervellati, Claudia Sticozzi, Giuseppe Belmonte, Chung Hin Chui, Ilaria Lampronti, Monica Borgatti, Roberto Gambari, and Giuseppe Valacchi Copyright © 2015 Ximena M. Muresan et al. All rights reserved. CO2 Pneumoperitoneum Preserves β-Arrestin 2 Content and Reduces High Mobility Group Box-1 (HMGB-1) Expression in an Animal Model of Peritonitis Tue, 24 Feb 2015 07:09:10 +0000 http://www.hindawi.com/journals/omcl/2015/160568/ Laparoscopy (LS) has been shown to decrease the inflammatory sequelae of endotoxemia. β-arrestin 2 plays an important function in signal transduction pathway of TLR4. High mobility group box-1 (HMGB-1) is involved in the delayed systemic inflammatory response. We investigated the effects of CO2 insufflation on liver, lung, and kidney expression of both β-arrestin 2 and HMGB-1 during sepsis. Cecal ligation and puncture (CLP) was performed in male rats and 6 h later the animals were randomly assigned to receive a CO2 pneumoperitoneum or laparotomy. Animals were euthanized; liver, lung, and kidney were removed for the evaluation of β-arrestin 2 and HMGB-1 expression. Immunohistochemical detection of myeloperoxidase (MPO) was investigated in lung and liver and bacterial load was determined in the peritoneal fluid. CO2 pneumoperitoneum reduced peritoneal bacterial load, increased the expression of β-arrestin 2, and blunted the expression of the potent proinflammatory HMGB-1 in liver, lung, and kidney compared with laparotomy. Liver and lung MPO was markedly reduced in rats subjected to LS compared with laparotomy. We believe that CO2 exerts an early protective effect by reducing bacterial load and likely toll-like receptor activation which in turn leads to a preserved β-arrestin 2 expression and a reduced HMGB-1 expression. Angela Simona Montalto, Alessandra Bitto, Letteria Minutoli, Pietro Impellizzeri, Gaetano Costa, Natasha Irrera, Gabriele Pizzino, Francesco Squadrito, Domenica Altavilla, and Carmelo Romeo Copyright © 2015 Angela Simona Montalto et al. All rights reserved. Influence of Vitamin C Supplementation on Oxidative Stress and Neutrophil Inflammatory Response in Acute and Regular Exercise Mon, 23 Feb 2015 16:46:14 +0000 http://www.hindawi.com/journals/omcl/2015/295497/ Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO) in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP)) and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA), MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group) and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group. Ljiljana M. Popovic, Nebojsa R. Mitic, Dijana Miric, Boban Bisevac, Mirjana Miric, and Brankica Popovic Copyright © 2015 Ljiljana M. Popovic et al. All rights reserved. Urinary F2-Isoprostanes and Metabolic Markers of Fat Oxidation Mon, 23 Feb 2015 08:57:51 +0000 http://www.hindawi.com/journals/omcl/2015/729191/ Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n = 682). Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index) and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and −0.094, respectively (P < 0.05). For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs) of incident diabetes are calculated from logistic regression models: the ORs (95% CI) are 0.77 (0.60–0.97), 0.79 (0.62–1.01), 1.18 (0.92–1.53), and 0.51 (0.35–0.76) for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12) supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation. Dora Il’yasova, Lynne E. Wagenknecht, Ivan Spasojevic, Steven Watkins, Donald Bowden, Frances Wang, and Ralph B. D’Agostino Jr. Copyright © 2015 Dora Il’yasova et al. All rights reserved. DNA Damage and Inhibition of Akt Pathway in MCF-7 Cells and Ehrlich Tumor in Mice Treated with 1,4-Naphthoquinones in Combination with Ascorbate Sun, 22 Feb 2015 09:58:03 +0000 http://www.hindawi.com/journals/omcl/2015/495305/ The aim of this study was to enhance the understanding of the antitumor mechanism of 1,4-naphthoquinones and ascorbate. Juglone, phenylaminonaphthoquinone-7, and 9 (Q7/Q9) were evaluated for effects on CT-DNA and DNA of cancer cells. Evaluations in MCF-7 cells are DNA damage, ROS levels, viability, and proliferation. Proteins from MCF-7 lysates were immunoblotted for verifying PARP integrity, γH2AX, and pAkt. Antitumor activity was measured in Ehrlich ascites carcinoma-bearing mice. The same markers of molecular toxicity were assessed in vivo. The naphthoquinones intercalate into CT-DNA and caused oxidative cleavage, which is increased in the presence of ascorbate. Treatments caused DNA damage and reduced viability and proliferation of MCF-7 cells. Effects were potentiated by ascorbate. No PARP cleavage was observed. Naphthoquinones, combined with ascorbate, caused phosphorylation of H2AX and inhibited pAkt. ROS were enhanced in MCF-7 cells, particularly by the juglone and Q7 plus ascorbate. Ehrlich carcinoma was inhibited by juglone, Q7, or Q9, but the potentiating effect of ascorbate was reproduced in vivo only in the cases of juglone and Q7, which caused up to 60% inhibition of tumor and the largest extension of survival. Juglone and Q7 plus ascorbate caused enhanced ROS and DNA damage and inhibited pAkt also in Ehrlich carcinoma cells. Fabiana Ourique, Maicon R. Kviecinski, Karina B. Felipe, João Francisco Gomes Correia, Mirelle S. Farias, Luiza S. E. P. W. Castro, Valdelúcia M. A. S. Grinevicius, Jaime Valderrama, David Rios, Julio Benites, Pedro Buc Calderon, and Rozangela Curi Pedrosa Copyright © 2015 Fabiana Ourique et al. All rights reserved. Dry Olive Leaf Extract Counteracts L-Thyroxine-Induced Genotoxicity in Human Peripheral Blood Leukocytes In Vitro Thu, 19 Feb 2015 19:11:34 +0000 http://www.hindawi.com/journals/omcl/2015/762192/ The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger. Dijana Žukovec Topalović, Lada Živković, Andrea Čabarkapa, Ninoslav Djelić, Vladan Bajić, Dragana Dekanski, and Biljana Spremo-Potparević Copyright © 2015 Dijana Žukovec Topalović et al. All rights reserved. Physical Exercise and Redox Balance in Type 2 Diabetics: Effects of Moderate Training on Biomarkers of Oxidative Stress and DNA Damage Evaluated through Comet Assay Thu, 19 Feb 2015 13:05:34 +0000 http://www.hindawi.com/journals/omcl/2015/981242/ Objective. Hyperglycemia leads to increased production of reactive oxygen species (ROS) in type 2 diabetes, which reduces cellular antioxidant defenses and induces DNA lesions. The aim of this study was to investigate the effects on redox homeostasis and DNA oxidative damage of exercise training in patients with type 2 diabetes compared with nondiabetic individuals. Methods and Results. 12 sedentary type 2 diabetic males (62.1 ± 4.3 yrs) and 12 sedentary healthy males (61.7 ± 3.9 yrs) were exposed to 4-month moderate training, 3 times per week, to evaluate the effect on plasma biomarkers of oxidative stress malondialdehyde and antioxidant status (GSSG, GSH/GSSG, and ascorbic acid) as well as basal and H2O2-induced DNA damage trough alkaline comet assay in peripheral blood lymphocytes. After training, glutathione and ascorbic acid levels increased in both groups, but only in diabetics the malondialdehyde as well as the DNA damage decreased. Conclusion. Our study demonstrates for the first time that moderate exercise training is not only effective in improving the redox homeostasis, through an increase of the endogenous antioxidant defences in healthy as well as in diabetic patients, but also, specifically in diabetic patients, effective in lowering the susceptibility to oxidative DNA damage and the lipid peroxidation levels. Monica Pittaluga, Antonio Sgadari, Ivan Dimauro, Barbara Tavazzi, Paolo Parisi, and Daniela Caporossi Copyright © 2015 Monica Pittaluga et al. All rights reserved. Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling Wed, 18 Feb 2015 08:45:29 +0000 http://www.hindawi.com/journals/omcl/2015/867293/ Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling. Dayong Zhang, Bingxi Yan, Shanshan Yu, Chong Zhang, Baoming Wang, Yayan Wang, Junbo Wang, Zhanggen Yuan, Lihuang Zhang, and Jianping Pan Copyright © 2015 Dayong Zhang et al. All rights reserved. Potential Benefits of Berberine in the Management of Perimenopausal Syndrome Tue, 17 Feb 2015 11:32:06 +0000 http://www.hindawi.com/journals/omcl/2015/723093/ Cardiovascular diseases are one of the leading causes of morbidity and mortality in women after menopause and 56% of all causes of death in Western European countries. Nowadays, with increasing life span, women spend approximately one-third of their life-time in postmenopausal state; therefore, the development of new strategies to improve the prevention and treatment of menopause-associated pathologies is important topic in clinical practice. The studies to assess the safety of hormone replacement therapy in women with estrogen deficiency have not been conclusive due to the relative contraindications; therefore, hormone replacement therapy is prescribed only in selected cases and for a limited time. For this reason, today women are encouraged to use naturally available compounds to prevent or to attenuate menopausal symptoms and correlated pathologies, with fewer side effects. Among these compounds, berberine, an isoquinoline alkaloid derived from plants of the generis Berberis, has been recognized as being capable of decreasing oxidative stress, LDL, triglycerides, and insulin resistance and of improving the mood. This review describes the cellular and clinical effects associated with the use of berberine, which suggest that this molecule could be an effective natural supplement to ensure a smooth peri- and postmenopausal transition. Cristiana Caliceti, Paola Rizzo, and Arrigo Francesco Giuseppe Cicero Copyright © 2015 Cristiana Caliceti et al. All rights reserved. Hyperhomocysteinemia and MTHFR Polymorphisms as Antenatal Risk Factors of White Matter Abnormalities in Two Cohorts of Late Preterm and Full Term Newborns Tue, 10 Feb 2015 12:54:08 +0000 http://www.hindawi.com/journals/omcl/2015/543134/ Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born <37 wks, and 126 (73.7%) born ≥37 wks were recruited in the study. cUS detected predominant WMA pattern in 36/171 newborns (21.1%) mainly characterized by abnormal periventricular white matter signal and mild-to-moderate periventricular white matter volume loss with ventricular dilatation (6/36, 16.6%). WMA resulted in being depending on tHcy levels , lower GA , lower Apgar score at 1 minutes and 5 minutes , and 1298AC and 677CT/1298AC genotypes ( and ). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling. Lucia M. Marseglia, Antonio Nicotera, Vincenzo Salpietro, Elisa Giaimo, Giovanna Cardile, Maria Bonsignore, Angela Alibrandi, Daniela Caccamo, Sara Manti, Gabriella D’Angelo, Carmelo Mamì, and Gabriella Di Rosa Copyright © 2015 Lucia M. Marseglia et al. All rights reserved. Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma Mon, 09 Feb 2015 08:13:43 +0000 http://www.hindawi.com/journals/omcl/2015/593658/ Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa. Tatiana I. Ivanova, Ludmila I. Krikunova, Nikolay I. Ryabchenko, Liana S. Mkrtchyan, Vera A. Khorokhorina, and Lyubov E. Salnikova Copyright © 2015 Tatiana I. Ivanova et al. All rights reserved. Blue-Violet Light Irradiation Dose Dependently Decreases Carotenoids in Human Skin, Which Indicates the Generation of Free Radicals Mon, 09 Feb 2015 06:23:15 +0000 http://www.hindawi.com/journals/omcl/2015/579675/ In contrast to ultraviolet and infrared irradiation, which are known to facilitate cutaneous photoaging, immunosuppression, or tumour emergence due to formation of free radicals and reactive oxygen species, potentially similar effects of visible light on the human skin are still poorly characterized. Using a blue-violet light irradiation source and aiming to characterize its potential influence on the antioxidant status of the human skin, the cutaneous carotenoid concentration was measured noninvasively in nine healthy volunteers using resonance Raman spectroscopy following irradiation. The dose-dependent significant degradation of carotenoids was measured to be 13.5% and 21.2% directly after irradiation at 50 J/cm² and 100 J/cm² (). The irradiation intensity was 100 mW/cm². This is above natural conditions; the achieved doses, though, are acquirable under natural conditions. The corresponding restoration lasted 2 and 24 hours, respectively. The degradation of cutaneous carotenoids indirectly shows the amount of generated free radicals and especially reactive oxygen species in human skin. In all volunteers the cutaneous carotenoid concentration dropped down in a manner similar to that caused by the infrared or ultraviolet irradiations, leading to the conclusion that also blue-violet light at high doses could represent a comparably adverse factor for human skin. Staffan Vandersee, Marc Beyer, Juergen Lademann, and Maxim E. Darvin Copyright © 2015 Staffan Vandersee et al. All rights reserved. A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury Wed, 04 Feb 2015 13:55:38 +0000 http://www.hindawi.com/journals/omcl/2015/607271/ The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1α) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1α/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1α pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1α/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure. Jia Xiao, Yi Lv, Bin Lin, George L. Tipoe, Moussa B. H. Youdim, Feiyue Xing, and Yingxia Liu Copyright © 2015 Jia Xiao et al. All rights reserved. Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression Wed, 04 Feb 2015 13:49:13 +0000 http://www.hindawi.com/journals/omcl/2015/426069/ Ischemic stroke interrupts the flow of blood to the brain and subsequently results in cerebral infarction and neuronal cell death, leading to severe pathophysiology. Glutathione (GSH) is an antioxidant with cellular protective functions, including reactive oxygen species (ROS) scavenging in the brain. In addition, GSH is involved in various cellular survival pathways in response to oxidative stress. In the present study, we examined whether GSH reduces cerebral infarct size after middle cerebral artery occlusion in vivo and the signaling mechanisms involved in the promotion of cell survival after GSH treatment under ischemia/reperfusion conditions in vitro. To determine whether GSH reduces the extent of cerebral infarction, cell death after ischemia, and reperfusion injury, we measured infarct size in ischemic brain tissue and the expression of claudin-5 associated with brain infarct formation. We also examined activation of the PI3K/Akt pathway, inactivation of FOXO3, and expression of Bcl2 to assess the role of GSH in promoting cell survival in response to ischemic injury. Based on our results, we suggest that GSH might improve the pathogenesis of ischemic stroke by attenuating cerebral infarction and cell death. Juhyun Song, Joohyun Park, Yumi Oh, and Jong Eun Lee Copyright © 2015 Juhyun Song et al. All rights reserved. Effects of Concurrent Training on Oxidative Stress and Insulin Resistance in Obese Individuals Wed, 04 Feb 2015 10:46:04 +0000 http://www.hindawi.com/journals/omcl/2015/697181/ Obesity is associated with insulin resistance (IR) and increased oxidative stress. Thus, the present study aimed to evaluate anthropometric parameters, IR, and oxidative stress in obese individuals subjected to two types of concurrent training at the same intensity but differing in frequency. Accordingly, 25 individuals were divided into two groups: concurrent training 1 (CT1) (5 d/wk) and concurrent training 2 (CT2) (3 d/wk), both with moderate intensity. Anthropometric parameters, IR, and oxidative stress were analyzed before and after 26 sessions of training. Both groups had reduced body weight and body mass index (), but only CT1 showed lower body fat percentage and increased basal metabolic rate (). Moreover, CT1 had increased HOMA-IR and decreased protein damage (carbonyl level), and CT2 had decreased HOMA-IR and increased lipid peroxidation (TBARS level) (). On the other hand, both training protocols reduced the GPx activity. It can be concluded that both types of concurrent training could be an alternative for lowering body weight and BMI. Also, it was observed that concurrent training, depending on the frequency, can contribute to reducing body fat, oxidative damage (protein oxidation), and IR but can induce oxidative damage to lipids. More studies are needed to elucidate the mechanisms involved. Niara da Silva Medeiros, Fabiana Guichard de Abreu, Alana Schraiber Colato, Leandro Silva de Lemos, Thiago Rozales Ramis, Gilson Pires Dorneles, Cláudia Funchal, and Caroline Dani Copyright © 2015 Niara da Silva Medeiros et al. All rights reserved. Cardiopulmonary Bypass and Oxidative Stress Wed, 04 Feb 2015 07:01:53 +0000 http://www.hindawi.com/journals/omcl/2015/189863/ The development of the cardiopulmonary bypass (CPB) revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress. Mustafa Zakkar, Gustavo Guida, M-Saadeh Suleiman, and Gianni D. Angelini Copyright © 2015 Mustafa Zakkar et al. All rights reserved. Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy Mon, 02 Feb 2015 13:22:00 +0000 http://www.hindawi.com/journals/omcl/2015/632902/ The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis. Seahyoung Lee, Eunhyun Choi, Min-Ji Cha, and Ki-Chul Hwang Copyright © 2015 Seahyoung Lee et al. All rights reserved. A New Approach to Oxidative Stress and Inflammatory Signaling during Labour in Healthy Mothers and Neonates Sun, 01 Feb 2015 11:43:34 +0000 http://www.hindawi.com/journals/omcl/2015/178536/ The objective of the current study was to investigate for the first time and simultaneously the oxidative stress and inflammatory signaling induced during the delivery in healthy mothers and their neonates. 56 mothers with normal gestational course and spontaneous delivery were selected. Blood samples were taken from mother (before and after delivery) both from vein and artery of umbilical cord. Lower antioxidant enzymes activities were observed in neonates compared with their mothers and lower oxidative stress in umbilical cord artery with respect to vein. There was an overexpression of inflammatory cytokines in the mother, such as IL-6 and TNF-α, and, in addition, PGE2 was also increased. Neonates showed lower levels of IL-6 and TNF-α and higher values of sTNF-RII and PGE2 in comparison with their mothers. Parturition increases oxidative damage in the mother, although the indicators of oxidative damage were lower in umbilical cord artery with respect to umbilical vein. The overexpression of inflammatory cytokines reveals that fetus suffers its own inflammatory process during parturition. Javier Díaz-Castro, Jesus Florido, Naroa Kajarabille, Sonia Prados, Catalina de Paco, Olga Ocon, Mario Pulido-Moran, and Julio J. Ochoa Copyright © 2015 Javier Díaz-Castro et al. All rights reserved. Xanthine Oxidoreductase Reference Values in Platelet-Poor Plasma and Platelets in Healthy Volunteers Tue, 20 Jan 2015 08:48:19 +0000 http://www.hindawi.com/journals/omcl/2015/341926/ Introduction. Xanthine oxidoreductase (XOR) is an enzyme belonging to the class of hydroxylases. XOR is stated, inter alia, in the kidneys, liver, and small intestine as well as in leukocytes and platelets and endothelial cells of capillaries. Its main role is to participate in the conversion of hypoxanthine to xanthine and the uric acid. It occurs in two isoforms: dehydrogenase (XD) and oxidase (XO), which is considered one of the sources of reactive oxygen species. Aim of the Study. Determination of reference values of xanthine oxidoreductase activity in PPP and platelets. Materials and Methods. Study group consisted of 70 healthy volunteers. The isoform activities of xanthine oxidoreductase were determined by kinetic spectrophotometry. Results. A statistically significant difference between the activity of the XOR in PPP and platelets (). The highest activity of XO was found in both PPP and blood platelets. Significant differences between the activity of the various isoforms in PPP () and platelets () were also found. Conclusions. The healthy volunteers showed the highest activity XO (prooxidant) and the lowest XD (antioxidant), which indicates a slight oxidative stress and confirmed physiological effects of XOR. Elżbieta Cecerska-Heryć, Anna Jesionowska, Szupiluk Klaudyna, Siewierska Katarzyna, Mączka Dominika, Pawlak Dominika, Urbańska Marta, and Barbara Dołęgowska Copyright © 2015 Elżbieta Cecerska-Heryć et al. All rights reserved. Naphthoquinone Derivative PPE8 Induces Endoplasmic Reticulum Stress in p53 Null H1299 Cells Sun, 18 Jan 2015 14:22:57 +0000 http://www.hindawi.com/journals/omcl/2015/453679/ Endoplasmic reticulum (ER) plays a key role in synthesizing secretory proteins and sensing signal function in eukaryotic cells. Responding to calcium disturbance, oxidation state change, or pharmacological agents, ER transmembrane protein, inositol-regulating enzyme 1 (IRE1), senses the stress and triggers downstream signals. Glucose-regulated protein 78 (GRP78) dissociates from IRE1 to assist protein folding and guard against cell death. In prolonged ER stress, IRE1 recruits and activates apoptosis signal-regulating kinase 1 (ASK1) as well as downstream JNK for cell death. Naphthoquinones are widespread natural phenolic compounds. Vitamin K3, a derivative of naphthoquinone, inhibits variant tumor cell growth via oxygen uptake and oxygen stress. We synthesized a novel naphthoquinone derivative PPE8 and evaluated capacity to induce ER stress in p53 null H1299 and p53 wild-type A549 cells. In H1299 cells, PPE8 induced ER enlargement, GRP78 expression, and transient IER1 activation. Activated IRE1 recruited ASK1 for downstream JNK phosphorylation. IRE1 knockdown by siRNA attenuated PPE8-induced JNK phosphorylation and cytotoxicity. Prolonged JNK phosphorylation may be involved in PPE8-induced cytotoxicity. Such results did not arise in A549 cells, but p53 knockdown by siRNA restored PPE8-induced GRP78 expression and JNK phosphorylation. We offer a novel compound to induce ER stress and cytotoxicity in p53-deficient cancer cells, presenting an opportunity for treatment. Jin-Cherng Lien, Chien-Chun Huang, Te-Jung Lu, Chih-Hsiang Tseng, Ping-Jyun Sung, Hong-Zin Lee, Bo-Ying Bao, Yueh-Hsiung Kuo, and Te-Ling Lu Copyright © 2015 Jin-Cherng Lien et al. All rights reserved. The Synergistic Effects of Heat Shock Protein 70 and Ginsenoside Rg1 against Tert-Butyl Hydroperoxide Damage Model In Vitro Thu, 15 Jan 2015 11:13:39 +0000 http://www.hindawi.com/journals/omcl/2015/437127/ Neural stem cells (NSCs) transplanted is one of the hottest research to treat Alzheimer’s disease (AD), but cholinergic neurons from stem cells were also susceptible to cell death which Heat shock protein 70 (HSP70) was affirmed to reverse. Related to cognitive impairment, cholinergic nervous cells should be investigated and ginsenoside Rg1 (G-Rg1) was considered to increase them. We chose tert-butyl hydroperoxide (t-BHP) damage model to study in vitro. Functional properties of our recombination plasmid pEGFP-C2-HSP70 were affirmed by SH-SY5Y cells. To opposite the transitory appearance of HSP70, NSCs used as the vectors of HSP70 gene overexpressed HSP70 for at least 7 days in vitro. After transfection for 3 days, G-Rg1 pretreatment for 4 hours, and coculture for 3 days, the expression of acetylcholinesterase (ChAT), synaptophysin, and the ratio of NeuN and GFAP were assessed by western blot; Morphological properties were detected by 3D reconstruction and immunofluorescence. ChAT was markedly improved in the groups contained G-Rg1. In coculture system, the ratio of neurons/astrocytes and the filaments of neurons were increased; apoptosis cells were decreased, compared to monotherapy (). In conclusion, we demonstrated that, as a safe cotreatment affirmed in vitro, overexpression of HSP70 in NSCs plus G-Rg1 promoted nervous cells regeneration from chronic oxidative damage. Dan Lu, Anding Xu, Hongcheng Mai, Jiayi Zhao, Chanjuan Zhang, Renbin Qi, Huadong Wang, Daxiang Lu, and Lihong Zhu Copyright © 2015 Dan Lu et al. All rights reserved. Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain Tue, 13 Jan 2015 09:56:19 +0000 http://www.hindawi.com/journals/omcl/2015/530371/ Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight) and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable. Marco Sifringer, Clarissa von Haefen, Maria Krain, Nadine Paeschke, Ivo Bendix, Christoph Bührer, Claudia D. Spies, and Stefanie Endesfelder Copyright © 2015 Marco Sifringer et al. All rights reserved. Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK/NF-κB-Dependent Mechanism Mon, 12 Jan 2015 14:00:58 +0000 http://www.hindawi.com/journals/omcl/2015/934058/ Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases. Yan Zhao, Si-jia Chen, Jian-cheng Wang, Hong-xin Niu, Qian-qian Jia, Xiao-wen Chen, Xiao-yan Du, Lu Lu, Bo Huang, Quan Zhang, Yue Chen, and Hai-bo Long Copyright © 2015 Yan Zhao et al. All rights reserved.