Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Exercise Training Preserves Ischemic Preconditioning in Aged Rat Hearts by Restoring the Myocardial Polyamine Pool Thu, 23 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2014/457429/ Background. Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool. Methods. Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol. Results. IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor, α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunction in vitro. Conclusion. Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus. Weiwei Wang, Hao Zhang, Guo Xue, Li Zhang, Weihua Zhang, Lina Wang, Fanghao Lu, Hongzhu Li, Shuzhi Bai, Yan Lin, Yu Lou, Changqing Xu, and Yajun Zhao Copyright © 2014 Weiwei Wang et al. All rights reserved. Reduced Oxidative Stress Contributes to the Lipid Lowering Effects of Isoquercitrin in Free Fatty Acids Induced Hepatocytes Wed, 22 Oct 2014 09:10:58 +0000 http://www.hindawi.com/journals/omcl/2014/313602/ Oxidative stress interferes with hepatic lipid metabolism at various levels ranging from benign lipid storage to so-called second hit of inflammation activation. Isoquercitrin (IQ) is widely present flavonoid but its effects on hepatic lipid metabolism remain unknown. We used free fatty acids (FFA) induced lipid overload and oxidative stress model in two types of liver cells and measured cell viability, intracellular lipids, and reactive oxygen species (ROS) within hepatocytes. In addition, Intracellular triglycerides (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) were examined. A novel in vitro model was used to evaluate correlation between lipid lowering and antioxidative activities. Furthermore, 34 major cytokines and corresponding ROS levels were analyzed in FFA/LPS induced coculture model between hepatocytes and Kupffer cells. At molecular level AMPK pathway was elucidated. We showed that IQ attenuated FFA induced lipid overload and ROS within hepatocytes. Further, IQ reversed FFA induced increase in intracellular TG SOD and MDA. It was shown that antioxidative activity of IQ correlates with its lipid lowering potentials. IQ reversed major proinflammatory cytokines and oxidative stress in FFA/LPS induced coculture model. Finally, AMPK pathway was found responsible for metabolic benefits at molecular level. IQ strikingly manifests antioxidative and related lipid lowering activities in hepatocytes. Waseem Hassan, Gao Rongyin, Abdelkader Daoud, Lin Ding, Lulu Wang, Jun Liu, and Jing Shang Copyright © 2014 Waseem Hassan et al. All rights reserved. Magnolin Protects against Contrast-Induced Nephropathy in Rats via Antioxidation and Antiapoptosis Tue, 21 Oct 2014 10:00:25 +0000 http://www.hindawi.com/journals/omcl/2014/203458/ Background. Magnolin is the major active ingredient of the herb Magnolia fargesii which has anti-inflammatory and antioxidative effects. Oxidative stress and apoptosis are involved in the pathogenesis of contrast-induced nephropathy (CIN). We hypothesize that Magnolin could protect against CIN through antioxidative and antiapoptotic properties. Methods. To test whether Magnolin could attenuate CIN, oxidative stress and apoptosis, in vivo and in vitro, we utilized a rat model of ioversol-induced CIN and a cell model of oxidative stress in which HK2 cells were treated with H2O2. Rats were assigned to 4 groups ( per group): control group, ioversol group (ioversol-induced CIN), vehicle group (CIN rats pretreated with vehicle), and Magnolin group (CIN rats pretreated with 1 mg/kg Magnolin). Results. The results showed that magnolin ameliorated the renal tubular necrosis, apoptosis, and the deterioration of renal function (). Furthermore, Magnolin reduced the renal oxidative stress, suppressed caspase-3 activity, and increased Bcl-2 expression in vivo and in vitro. Conclusion. Magnolin might protect CIN in rats through antioxidation and antiapoptosis. Feng Wang, Guangyuan Zhang, Yang Zhou, Dingkun Gui, Junhui Li, Tao Xing, and Niansong Wang Copyright © 2014 Feng Wang et al. All rights reserved. Astragalus Polysaccharide Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the PI3k/Akt and p38MAPK Pathways Thu, 16 Oct 2014 08:31:12 +0000 http://www.hindawi.com/journals/omcl/2014/674219/ Background. Doxorubicin, a potent chemotherapeutic agent, is associated with acute and chronic cardiotoxicity, which is cumulatively dose-dependent. Astragalus polysaccharide (APS), the extract of Astragalus membranaceus with strong antitumor and antiglomerulonephritis activity, can effectively alleviate inflammation. However, whether APS could ameliorate chemotherapy-induced cardiotoxicity is not understood. Here, we investigated the protective effects of APS on doxorubicin-induced cardiotoxicity and elucidated the underlying mechanisms of the protective effects of APS. Methods. We analyzed myocardial injury in cancer patients who underwent doxorubicin chemotherapy and generated a doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart failure model. Echocardiography, reactive oxygen species (ROS) production, TUNEL, DNA laddering, and Western blotting were performed to observe cell survival, oxidative stress, and inflammatory signal pathways in cardiomyocytes. Results. Treatment of patients with the chemotherapeutic drug doxorubicin led to heart dysfunction. Doxorubicin reduced cardiomyocyte viability and induced C57BL/6J mouse heart failure with concurrent elevated ROS generation and apoptosis, which, however, was attenuated by APS treatment. In addition, there was profound inhibition of p38MAPK and activation of Akt after APS treatment. Conclusions. These results demonstrate that APS could suppress oxidative stress and apoptosis, ameliorating doxorubicin-mediated cardiotoxicity by regulating the PI3k/Akt and p38MAPK pathways. Yuan Cao, Yang Ruan, Tao Shen, Xiuqing Huang, Meng Li, Weiwei Yu, Yuping Zhu, Yong Man, Shu Wang, and Jian Li Copyright © 2014 Yuan Cao et al. All rights reserved. Oxidative Status Imbalance in Patients with Metabolic Syndrome: Role of the Myeloperoxidase/Hydrogen Peroxide Axis Wed, 15 Oct 2014 09:01:50 +0000 http://www.hindawi.com/journals/omcl/2014/898501/ The present study evaluated the cardiometabolic and redox balance profiles in patients with Metabolic Syndrome compared to apparently healthy individuals, and the participation of the myeloperoxidase/hydrogen peroxide axis in systemic lipid peroxidation. Twenty-four patients with Metabolic Syndrome and eighteen controls underwent a full clinical assessment. Venous blood samples were collected for general biochemical dosages, as well as for the oxidative stress analyses (superoxide dismutase, catalase, and arginase activities; and lipid peroxidation, myeloperoxidase activity, nitrite, and hydrogen peroxide concentrations in plasma). Arterial stiffness was assessed by radial artery applanation tonometry. Plasma lipid peroxidation, erythrocyte superoxide dismutase activity, myeloperoxidase activity, and hydrogen peroxide concentrations were shown to be increased in Metabolic Syndrome patients, without significant differences for the other enzymes, plasma nitrite concentrations, and arterial stiffness. Linear regression analysis revealed a positive and significant correlation between lipid peroxidation and myeloperoxidase and also between this enzyme and hydrogen peroxide. In contrast, such correlation was not observed between lipid peroxidation and hydrogen peroxide. In summary, Metabolic Syndrome patients exhibited evident systemic redox imbalance compared to controls, with the possible participation of the myeloperoxidase/hydrogen peroxide axis as a contributor in lipid peroxidation. Lucas José Sá da Fonseca, Valéria Nunes-Souza, Glaucevane da Silva Guedes, Glauber Schettino-Silva, Marco Antônio Mota-Gomes, and Luíza Antas Rabelo Copyright © 2014 Lucas José Sá da Fonseca et al. All rights reserved. Electrochemically Reduced Water Protects Neural Cells from Oxidative Damage Tue, 14 Oct 2014 12:05:40 +0000 http://www.hindawi.com/journals/omcl/2014/869121/ Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2 (50–200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2 in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca2+ influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW. Taichi Kashiwagi, Hanxu Yan, Takeki Hamasaki, Tomoya Kinjo, Noboru Nakamichi, Kiichiro Teruya, Shigeru Kabayama, and Sanetaka Shirahata Copyright © 2014 Taichi Kashiwagi et al. All rights reserved. The Role of Oxidative Stress and the Effects of Antioxidants on the Incidence of Infectious Complications of Chronic Lymphocytic Leukemia Tue, 14 Oct 2014 09:55:49 +0000 http://www.hindawi.com/journals/omcl/2014/158135/ Chronic lymphocytic leukemia (CLL) is characterized by a predominant humoral immune deficiency predisposing the patients to infections. Oxidative stress leads to an increased immunoglobulin k light chain production in B cells and contributes to the antibodies’ deficiency and hypogammaglobulinemia. Aim of the Study. To evaluate the global oxidative status in patients with CLL and to determine whether the administration of antioxidants decreases complications due to infections. Patients and Method. We studied 84 patients with CLL stratified by Binet staging. Free oxygen radicals and antioxidant status were determined by the FORT and FORD test, respectively, at diagnosis and in the presence of infections. The patients were distributed in two groups: group A, treated only with antileukemic treatment, and group B, treated with antileukemic treatment and antioxidants. Results. By FORD and FORT assay, all patients had at diagnosis a low antioxidant capacity, and high levels of hydroperoxides. Infectious complications were more frequent in group A (B/C stages of disease) than in group B. Administrations of antioxidants stimulated the immune response and decreased infectious complications in CLL. Conclusions. Administrations of antioxidants and a healthy life style may improve the quality of life of patients with CLL and reduce the risk of infectious complications. Amelia Maria Gaman, Ana-Maria Buga, Mihnea-Alexandru Gaman, and Aurel Popa-Wagner Copyright © 2014 Amelia Maria Gaman et al. All rights reserved. PRAK Interacts with DJ-1 and Prevents Oxidative Stress-Induced Cell Death Tue, 14 Oct 2014 09:34:12 +0000 http://www.hindawi.com/journals/omcl/2014/735618/ As a core member of p38 MAPK signal transduction pathway, p38 regulated/activated kinase (PRAK) is activated by cellular stresses. However, the function of PRAK and its downstream interacting partner remain undefined. Using a yeast two-hybrid system, we identified DJ-1 as a potential PRAK interacting protein. We further verified that DJ-1 bound to PRAK in vitro and in vivo and colocalized with PRAK in the nuclei of NIH3T3 cells. Furthermore, following H2O2 stimulation the majority of endogenous DJ-1 in PRAK+/+ cells still remained in the nucleus, whereas most DJ-1 in PRAK−/− cells translocated from the nucleus into the cytoplasm, indicating that PRAK is essential for DJ-1 to localize in the nucleus. In addition, PRAK-associated phosphorylation of DJ-1 was observed in vitro and in vivo of H2O2-challenged PRAK+/+ cells. Cytoplasmic translocation of DJ-1 in H2O2-treated PRAK−/− cells lost its ability to sequester Daxx, a death protein, in the nucleus, and as a result, Daxx gained access to the cytoplasm and triggered cell death. These data highlight that DJ-1 is the downstream interacting target for PRAK, and in response to oxidative stress PRAK may exert a cytoprotective effect by facilitating DJ-1 to sequester Daxx in the nucleus, thus preventing cell death. Jing Tang, Jinghua Liu, Xue Li, Yuyun Zhong, Tianyu Zhong, Yawei Liu, Jiang Huai Wang, and Yong Jiang Copyright © 2014 Jing Tang et al. All rights reserved. PKCδ Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc Mon, 13 Oct 2014 12:10:43 +0000 http://www.hindawi.com/journals/omcl/2014/746531/ Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKCδ and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKCδ, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKCδ during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKCδ was increased in a dose- and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKCδ. Moreover, PKCδ siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKCδ promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient. Panai Song, Shikun Yang, Li Xiao, Xiaoxuan Xu, Chengyuan Tang, Yuyan Yang, Mingming Ma, Jiefu Zhu, Fuyou Liu, and Lin Sun Copyright © 2014 Panai Song et al. All rights reserved. Nonalcoholic Fatty Liver Disease: Pathogenesis and Therapeutics from a Mitochondria-Centric Perspective Mon, 13 Oct 2014 08:12:05 +0000 http://www.hindawi.com/journals/omcl/2014/637027/ Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of disorders characterized by the accumulation of triglycerides within the liver. The global prevalence of NAFLD has been increasing as the obesity epidemic shows no sign of relenting. Mitochondria play a central role in hepatic lipid metabolism and also are affected by upstream signaling pathways involved in hepatic metabolism. This review will focus on the role of mitochondria in the pathophysiology of NAFLD and touch on some of the therapeutic approaches targeting mitochondria as well as metabolically important signaling pathways. Mitochondria are able to adapt to lipid accumulation in hepatocytes by increasing rates of beta-oxidation; however increased substrate delivery to the mitochondrial electron transport chain (ETC) leads to increased reactive oxygen species (ROS) production and eventually ETC dysfunction. Decreased ETC function combined with increased rates of fatty acid beta-oxidation leads to the accumulation of incomplete products of beta-oxidation, which combined with increased levels of ROS contribute to insulin resistance. Several related signaling pathways, nuclear receptors, and transcription factors also regulate hepatic lipid metabolism, many of which are redox sensitive and regulated by ROS. Aaron M. Gusdon, Ke-xiu Song, and Shen Qu Copyright © 2014 Aaron M. Gusdon et al. All rights reserved. Protective Effect of Momordica charantia Fruit Extract on Hyperglycaemia-Induced Cardiac Fibrosis Mon, 13 Oct 2014 08:08:25 +0000 http://www.hindawi.com/journals/omcl/2014/429060/ In diabetes mellitus, cardiac fibrosis is characterized by increase in the deposition of collagen fibers. The present study aimed to observe the effect of Momordica charantia (MC) fruit extract on hyperglycaemia-induced cardiac fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single intravenous injection of streptozotocin (STZ). Following 4 weeks of STZ induction, the rats were subdivided (n = 6) into control group (Ctrl), control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated with MC (DM-MC), and diabetic group treated with 150 mg/kg of metformin (DM-Met). Administration of MC fruit extract (1.5 g/kg body weight) in diabetic rats for 28 days showed significant increase in the body weight and decrease in the fasting blood glucose level. Significant increase in cardiac tissues superoxide dismutase (SOD), glutathione contents (GSH), and catalase (CAT) was observed following MC treatment. Hydroxyproline content was significantly reduced and associated morphological damages reverted to normal. The decreased expression of type III and type IV collagens was observed under immunohistochemical staining. It is concluded that MC fruit extract possesses antihyperglycemic, antioxidative, and cardioprotective properties which may be beneficial in the treatment of diabetic cardiac fibrosis. Razif Abas, Faizah Othman, and Zar Chi Thent Copyright © 2014 Razif Abas et al. All rights reserved. Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury Mon, 13 Oct 2014 07:28:35 +0000 http://www.hindawi.com/journals/omcl/2014/215858/ Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co--photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit. Juliann G. Kiang, Min Zhai, Pei-Jyun Liao, Thomas B. Elliott, and Nikolai V. Gorbunov Copyright © 2014 Juliann G. Kiang et al. All rights reserved. Flutamide-Induced Cytotoxicity and Oxidative Stress in an In Vitro Rat Hepatocyte System Mon, 13 Oct 2014 07:25:40 +0000 http://www.hindawi.com/journals/omcl/2014/398285/ Flutamide (FLU) is a competitive antagonist of the androgen receptor which has been reported to induce severe liver injury in some patients. Several experimental models suggested that an episode of inflammation during drug treatment predisposes animals to tissue injury. The molecular cytotoxic mechanisms of FLU in isolated rat hepatocytes using an in vitro oxidative stress inflammation system were investigated in this study. When a nontoxic hydrogen peroxide (H2O2) generating system (glucose/glucose oxidase) with peroxidase or iron(II) [Fe(II)] (to partly simulate in vivo inflammation) was added to the hepatocytes prior to the addition of FLU, increases in FLU-induced cytotoxicity and lipid peroxidation (LPO) were observed that were decreased by 6-N-propyl-2-thiouracil or deferoxamine, respectively. N-Acetylcysteine decreased FLU-induced cytotoxicity in this system. Potent antioxidants, for example, Trolox ((±)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), resveratrol (3,5,4′-trihydroxy-trans-stilbene), and DPPD (N,N′-diphenyl-1,4-phenylenediamine) also significantly decreased FLU-induced cytotoxicity and LPO and increased mitochondrial membrane potential (MMP) and glutathione (GSH) levels in the H2O2 generating system with peroxidase. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl), a known reactive oxygen species (ROS) scavenger and superoxide dismutase mimetic, also significantly decreased toxicity caused by FLU in this system. These results raise the possibility that the presence or absence of inflammation may be another susceptibility factor for drug-induced hepatotoxicity. Abdullah Al Maruf and Peter O’Brien Copyright © 2014 Abdullah Al Maruf and Peter O’Brien. All rights reserved. A Quantitative Method to Monitor Reactive Oxygen Species Production by Electron Paramagnetic Resonance in Physiological and Pathological Conditions Sun, 12 Oct 2014 10:34:22 +0000 http://www.hindawi.com/journals/omcl/2014/306179/ The growing interest in the role of Reactive Oxygen Species (ROS) and in the assessment of oxidative stress in health and disease clashes with the lack of consensus on reliable quantitative noninvasive methods applicable. The study aimed at demonstrating that a recently developed Electron Paramagnetic Resonance microinvasive method provides direct evidence of the “instantaneous” presence of ROS returning absolute concentration levels that correlate with “a posteriori” assays of ROS-induced damage by means of biomarkers. The reliability of the choice to measure ROS production rate in human capillary blood rather than in plasma was tested (step I). A significant () linear relationship between EPR data collected on capillary blood versus venous blood (), plasma (), and erythrocytes () was found. Then (step II) ROS production changes of various subjects’ categories, young versus old and healthy versus pathological at rest condition, were found significantly different (range 0.0001–0.05 level). The comparison of the results with antioxidant capacity and oxidative damage biomarkers concentrations showed that all changes indicating increased oxidative stress are directly related to ROS production increase. Therefore, the adopted method may be an automated technique for a lot of routine in clinical trials. Simona Mrakic-Sposta, Maristella Gussoni, Michela Montorsi, Simone Porcelli, and Alessandra Vezzoli Copyright © 2014 Simona Mrakic-Sposta et al. All rights reserved. Hemin Attenuates Cisplatin-Induced Acute Renal Injury in Male Rats Mon, 22 Sep 2014 09:08:08 +0000 http://www.hindawi.com/journals/omcl/2014/476430/ Background. The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. Methods. The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. Results. A single intraperitoneal dose of CP (10 mg/kg b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. Conclusion. The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy. Mohamed A. Al-Kahtani, Ashraf M. Abdel-Moneim, Omar M. Elmenshawy, and Mohamed A. El-Kersh Copyright © 2014 Mohamed A. Al-Kahtani et al. 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.