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Poulios A, Papanikolaou K, Draganidis D, Tsimeas P, Chatzinikolaou A, Tsiokanos A, Jamurtas AZ, Fatouros IG. The Effects of Antioxidant Supplementation on Soccer Performance and Recovery: A Critical Review of the Available Evidence. Nutrients 2024; 16:3803. [PMID: 39599590 PMCID: PMC11597853 DOI: 10.3390/nu16223803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
Background Soccer is linked to an acute inflammatory response and the release of reactive oxygen species (ROS). Antioxidant supplements have shown promising effects in reducing muscle damage and oxidative stress and enhancing the recovery process after eccentric exercise. This critical review highlights the influence of antioxidant supplements on performance and recovery following soccer-related activity, training, or competition. Methods: English-language publications from the main databases that examine how antioxidant-based nutrition and supplements affect the recovery process before, during, and after soccer practice or competition were used. Results:Coenzyme Q10 (CoQ10), astaxanthin (Asx), red orange juice (ROJS), L-carnitine (LC), N-acetyl cysteine (NAC), beetroot (BET), turmeric root, and tangeretin reduce muscle damage (creatine kinase, myoglobin, cortisol, lactate dehudrogenase, muscle soreness). Tangeretin, docosahexaenoic acid (DHA), turmeric root, and aronia melanocarpa restrict inflammation (leukocytes, prostalagdin E2, C-reactive protein, IL-6 and 10). Q10, DHA, Asx, tangeretin, lippia citriodora, quercetin, allopurinol, turmeric root, ROJS, aronia melanocarpa, vitamins C-E, green tea (GTE), and sour tea (STE) reduce oxidative stress (malondialdehude, glutathione, total antioxidant capacity, superoxide dismutases, protein carbonyls, ascorbate, glutathione peroxidase, and paraoxonase 1). BET and NAC reinforce performance (endurance, jump, speed, strength). Conclusions: Further research is needed to determine the main mechanism and the acute and long-term impacts of antioxidant supplements in soccer.
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Affiliation(s)
- Athanasios Poulios
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
| | - Konstantinos Papanikolaou
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
| | - Dimitrios Draganidis
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
| | - Panagiotis Tsimeas
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
| | - Athanasios Chatzinikolaou
- Department of Physical Education and Sport Science, Democritus University of Thrace, 691 00 Komotini, Greece;
| | - Athanasios Tsiokanos
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
| | - Athanasios Z. Jamurtas
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
| | - Ioannis G. Fatouros
- Department of Physical Education and Sport Science, University of Thessaly, Karies, 382 21 Trikala, Greece; (A.P.); (K.P.); (D.D.)
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Andrés CMC, Pérez de la Lastra JM, Juan CA, Plou FJ, Pérez-Lebeña E. Myeloid-Derived Suppressor Cells in Cancer and COVID-19 as Associated with Oxidative Stress. Vaccines (Basel) 2023; 11:218. [PMID: 36851096 PMCID: PMC9966263 DOI: 10.3390/vaccines11020218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/14/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host. Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure. In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS. We here review the origin of MDSCs, their expansion mechanisms, and their suppressive functions in the context of cancer and COVID-19 associated with the presence of superoxide anion •O2- and reactive oxygen species ROS.
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Affiliation(s)
| | - José Manuel Pérez de la Lastra
- Cinquima Institute and Department of Organic Chemistry, Faculty of Sciences, Valladolid University, Paseo de Belén 7, 47011 Valladolid, Spain
| | - Celia Andrés Juan
- Institute of Natural Products and Agrobiology, CSIC-Spanish Research Council, Avda. Astrofísico Fco. Sánchez, 3, 38206 La Laguna, Spain
| | - Francisco J. Plou
- Institute of Catalysis and Petrochemistry, CSIC-Spanish Research Council, 28049 Madrid, Spain
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Altered Urinary Metabolomics in Hereditary Angioedema. Metabolites 2022; 12:metabo12111140. [PMID: 36422280 PMCID: PMC9696332 DOI: 10.3390/metabo12111140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/08/2022] [Accepted: 11/12/2022] [Indexed: 11/22/2022] Open
Abstract
Hereditary angioedema (HAE) is a rare and potentially life-threatening disease with heterogeneous clinical symptoms. The metabolomic profile of HAE remains unknown. Uncovering the metabolic signatures of HAE may provide inspiration for a comprehensive understanding of HAE pathogenesis and may help explore potential new metabolic biomarkers. We performed a comprehensive metabolic analysis using high-performance liquid chromatography−tandem mass spectrometry (HPLC-MS/MS). Urine samples from 34 HAE patients and 82 healthy controls (HCs) were collected to characterize the metabolic signatures associated with HAE. The metabolomes of HAE patients carrying different mutation types were also compared. A total of 795 metabolites were accurately detected and quantified. We considered 73 metabolites as differential metabolites in HAE patients (with an importance in projection (VIP) value > 1.0, q-value < 0.05, and fold change (FC) ≥ 1.2 or FC ≤ 0.8). Several metabolites associated with riboflavin metabolism, the citrate cycle, oxidative stress, and inflammation, including xanthine, oxypurinol, vitamin B2, and isocitrate, were significantly altered in HAE patients. No significantly different metabolites were found in HAE patients carrying different mutation types. The present study highlights that metabolic disturbances in the purine metabolism, riboflavin metabolism, and TCA cycle may be involved in the pathogenesis of HAE. Although biochemical significance requires further experimental verification, these findings may help to identify novel candidate metabolite biomarkers associated with HAE.
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Zhang Z, Dalan R, Hu Z, Wang JW, Chew NW, Poh KK, Tan RS, Soong TW, Dai Y, Ye L, Chen X. Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2202169. [PMID: 35470476 DOI: 10.1002/adma.202202169] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/08/2022] [Indexed: 06/14/2023]
Abstract
Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial-based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule-targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS-scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.
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Affiliation(s)
- Zhan Zhang
- Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China
| | - Rinkoo Dalan
- Department of Endocrinology, Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 408433, Singapore
| | - Zhenyu Hu
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
| | - Jiong-Wei Wang
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Department of Diagnostic Radiology and Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
| | - Nicholas Ws Chew
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, 119074, Singapore
| | - Kian-Keong Poh
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, 119074, Singapore
| | - Ru-San Tan
- Department of Cardiology, National Heart Centre Singapore, Singapore, 119609, Singapore
| | - Tuck Wah Soong
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
| | - Yunlu Dai
- Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China
- MoE Frontiers Science Center for Precision Oncology, University of Macao, Taipa, Macau SAR, 999078, China
| | - Lei Ye
- Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35294, USA
| | - Xiaoyuan Chen
- Department of Diagnostic Radiology and Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
- Department of Chemical and Biomolecular Engineering and Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, 117597, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore
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Foote CA, Soares RN, Ramirez-Perez FI, Ghiarone T, Aroor A, Manrique-Acevedo C, Padilla J, Martinez-Lemus LA. Endothelial Glycocalyx. Compr Physiol 2022; 12:3781-3811. [PMID: 35997082 PMCID: PMC10214841 DOI: 10.1002/cphy.c210029] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
The glycocalyx is a polysaccharide structure that protrudes from the body of a cell. It is primarily conformed of glycoproteins and proteoglycans, which provide communication, electrostatic charge, ionic buffering, permeability, and mechanosensation-mechanotransduction capabilities to cells. In blood vessels, the endothelial glycocalyx that projects into the vascular lumen separates the vascular wall from the circulating blood. Such a physical location allows a number of its components, including sialic acid, glypican-1, heparan sulfate, and hyaluronan, to participate in the mechanosensation-mechanotransduction of blood flow-dependent shear stress, which results in the synthesis of nitric oxide and flow-mediated vasodilation. The endothelial glycocalyx also participates in the regulation of vascular permeability and the modulation of inflammatory responses, including the processes of leukocyte rolling and extravasation. Its structural architecture and negative charge work to prevent macromolecules greater than approximately 70 kDa and cationic molecules from binding and flowing out of the vasculature. This also prevents the extravasation of pathogens such as bacteria and virus, as well as that of tumor cells. Due to its constant exposure to shear and circulating enzymes such as neuraminidase, heparanase, hyaluronidase, and matrix metalloproteinases, the endothelial glycocalyx is in a continuous process of degradation and renovation. A balance favoring degradation is associated with a variety of pathologies including atherosclerosis, hypertension, vascular aging, metastatic cancer, and diabetic vasculopathies. Consequently, ongoing research efforts are focused on deciphering the mechanisms that promote glycocalyx degradation or limit its syntheses, as well as on therapeutic approaches to improve glycocalyx integrity with the goal of reducing vascular disease. © 2022 American Physiological Society. Compr Physiol 12: 1-31, 2022.
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Affiliation(s)
- Christopher A. Foote
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA
| | - Rogerio N. Soares
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
| | | | - Thaysa Ghiarone
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
| | - Annayya Aroor
- Department of Medicine, University of Missouri, Columbia, MO, USA
- Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, USA
| | - Camila Manrique-Acevedo
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
- Department of Medicine, University of Missouri, Columbia, MO, USA
- Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, USA
| | - Jaume Padilla
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA
| | - Luis A. Martinez-Lemus
- Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA
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Vedder D, Gerritsen M, Nurmohamed MT, van Vollenhoven RF, Lood C. A neutrophil signature is strongly associated with increased cardiovascular risk in gout. Rheumatology (Oxford) 2021; 60:2783-2790. [PMID: 33188698 PMCID: PMC8213432 DOI: 10.1093/rheumatology/keaa712] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 10/07/2020] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To investigate the association between neutrophil activation and cardiovascular risk in gout patients. We hypothesize that neutrophil activation mediates inflammation and therefore takes part in atherogenesis in gout patients. METHOD Patient data were collected from 75 consecutive gout patients participating in the Reade gout cohort Amsterdam. Levels of neutrophil extracellular traps (NETs) and neutrophil activation (calprotectin and peroxidase activity) were analysed by ELISA and fluorimetry in plasma and compared with healthy controls. Markers of neutrophil activation were related to clinical markers of cardiovascular risk, including BMI, smoking, blood pressure, lipid profile and 10 year risk of cardiovascular mortality (EU-SCORE). RESULTS Increased levels of NETs were found in gout patients, although increased levels were not associated with cardiovascular risk. However, markers of neutrophil activation, including peroxidase activity correlated with waist:hip ratio (β = 0.33, P < 0.001), cholesterol ratio (β = 0.46, P < 0.005) and triglycerides (β = 0.60, P < 0.001) as well as the 10 year risk of cardiovascular mortality (β = 0.44, P = 0.001). Calprotectin levels were elevated in hypertension (P = 0.005) and diabetes (P = 0.02). Finally, gout patients with high levels of both peroxidase and calprotectin ('neutrophil activation signature') had a markedly elevated cardiovascular risk score (P = 0.001), with 68% of the patients having high cardiovascular risk (odds ratio 2.9, P = 0.03). CONCLUSION We demonstrated elevated levels of neutrophil activation markers, MPO and calprotectin in gout patients as compared with healthy controls. Of note, neutrophil activation markers were associated with several risk factors for cardiovascular disease, including hyperlipidaemia, hypertension and diabetes. Finally, the presence of a neutrophil activation signature was strongly associated with an increased 10 year risk of cardiovascular mortality. Further studies are needed to determine whether gout-specific factors and/or cardiovascular risk factors contribute to the elevated neutrophil activation observed in these patients.
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Affiliation(s)
- Daisy Vedder
- Amsterdam Rheumatology and Immunology Center Reade, Amsterdam, The Netherlands.,Vrije Universiteit, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Martijn Gerritsen
- Amsterdam Rheumatology and Immunology Center Reade, Amsterdam, The Netherlands
| | - Michael T Nurmohamed
- Amsterdam Rheumatology and Immunology Center Reade, Amsterdam, The Netherlands.,Vrije Universiteit, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.,Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Ronald F van Vollenhoven
- Amsterdam Rheumatology and Immunology Center Reade, Amsterdam, The Netherlands.,Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Christian Lood
- Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA
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Martorell M, Lucas X, Alarcón-Zapata P, Capó X, Quetglas-Llabrés MM, Tejada S, Sureda A. Targeting Xanthine Oxidase by Natural Products as a Therapeutic Approach for Mental Disorders. Curr Pharm Des 2021; 27:367-382. [PMID: 32564744 DOI: 10.2174/1381612826666200621165839] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/08/2020] [Indexed: 11/22/2022]
Abstract
Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.
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Affiliation(s)
- Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepcion, 4070386 Concepcion, Chile
| | - Xavier Lucas
- Roche Pharma Research and Early Development, Roche Innovation Center, Basel CH-4070, Switzerland
| | - Pedro Alarcón-Zapata
- Clinical Biochemistry and Immunology Department, Faculty of Pharmacy, University of Concepcion, 4070386 Concepcion, Chile
| | - Xavier Capó
- Research Group in Community Nutrition and Oxidative Stress, University of Balearic Islands & Health Research Institute of the Balearic Islands (IdISBa), E-07122, Palma, Balearic Islands, Spain
| | - Maria Magdalena Quetglas-Llabrés
- Laboratory of Neurophysiology, Department of Biology, University of Balearic Islands & Health Research Institute of the Balearic Islands (IdISBa), E-07122, Palma, Balearic Islands, Spain
| | - Silvia Tejada
- Laboratory of Neurophysiology, Department of Biology, University of Balearic Islands & Health Research Institute of the Balearic Islands (IdISBa), E-07122, Palma, Balearic Islands, Spain
| | - Antoni Sureda
- Research Group in Community Nutrition and Oxidative Stress, University of Balearic Islands & Health Research Institute of the Balearic Islands (IdISBa), E-07122, Palma, Balearic Islands, Spain
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Functions of ROS in Macrophages and Antimicrobial Immunity. Antioxidants (Basel) 2021; 10:antiox10020313. [PMID: 33669824 PMCID: PMC7923022 DOI: 10.3390/antiox10020313] [Citation(s) in RCA: 312] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 02/07/2023] Open
Abstract
Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors.
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Singh JA, Cleveland JD. Gout and the risk of age-related macular degeneration in the elderly. PLoS One 2018; 13:e0199562. [PMID: 30001351 PMCID: PMC6042699 DOI: 10.1371/journal.pone.0199562] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 06/08/2018] [Indexed: 02/07/2023] Open
Abstract
Objective To assess whether gout is associated with incident age-related macular degeneration (AMD) Methods We used the 5% Medicare claims data from 2006–12 for all beneficiaries who were enrolled in Medicare fee-for-service (Parts A, B) and not enrolled in a Medicare Advantage Plan, and resided in the U.S. People were censored at the occurrence of new diagnosis of AMD, death or the end of study (12/31/2012), whichever occurred first. We used multivariable-adjusted Cox regression analyses to assess the association of gout with incident AMD, adjusted for demographics, comorbidity, and use of medications for cardiovascular disease and gout. Hazard ratios and 95% confidence intervals were calculated. Results In this observational cohort study, of the 1,684,314 eligible people, 116,097 developed incident AMD (6.9%). Incidence rates of AMD per 1,000 person-years were 20.1 for people with gout and 11.7 for people without gout. In multivariable-adjusted analyses, a diagnosis of gout was significantly associated with a higher risk of incident AMD with a hazard ratio of 1.39 (95% CI, 1.35, 1.43). This association was confirmed in sensitivity analyses that substituted Charlson-Romano comorbidity index continuous score with either a categorical Charlson-Romano comorbidity index score or individual Charlson-Romano index comorbidities plus hypertension, hyperlipidemia and coronary artery disease. Other covariates significantly associated with higher hazards of incident AMD were older age, female gender, White race/ethnicity, and higher Charlson-Romano comorbidity index score. Conclusions We noted a novel association of gout with AMD in the elderly. Future studies should investigate the pathways that mediate this association.
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Affiliation(s)
- Jasvinder A Singh
- Medicine Service, VA Medical Center, Birmingham, Alabama, United States of America.,Department of Medicine at the School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, United States of America.,Department of Epidemiology at the UAB School of Public Health, Birmingham, Alabama, United States of America
| | - John D Cleveland
- Department of Medicine at the School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, United States of America
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Klisic A, Kocic G, Kavaric N, Jovanovic M, Stanisic V, Ninic A. Xanthine oxidase and uric acid as independent predictors of albuminuria in patients with diabetes mellitus type 2. Clin Exp Med 2017; 18:283-290. [PMID: 29214397 DOI: 10.1007/s10238-017-0483-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2017] [Accepted: 12/04/2017] [Indexed: 02/07/2023]
Abstract
Xanthine oxidase (XO) is an important enzyme responsible for conversion of purine bases to uric acid and represents the major source of reactive oxygen species (ROS) production in circulation. Since pathophysiological mechanism of the relationship between XO activity and urinary albumin excretion (UAE) rate is not well elucidated, we aimed to investigate this association in patients with diabetes mellitus type 2 (DM2). In addition, we wanted to examine whether uric acid itself plays an independent role in albuminuria onset and progression, or it is only mediated through XO activity. A total of 83 patients with DM2 (of them 56.6% females) were included in this cross-sectional study. Anthropometric, biochemical parameters and blood pressure were obtained. Multivariate logistic regression analysis showed that uric acid and XO were the independent predictors for albuminuria onset in patients with DM2 [odds ratio (OR) 1.015, 95% CI (1.008-1.028), p = 0.026 and OR 1.015, 95% CI (1.006-1.026), p = 0.040, respectively]. Rise in uric acid for 1 µmol/L enhanced the probability for albuminuria by 1.5%. Also, elevation in XO activity for 1 U/L increased the probability for albuminuria for 1.5%. A total of 66.7% of variation in UAE could be explained with this Model. Both XO and uric acid are independently associated with albuminuria in diabetes. Better understanding of pathophysiological relationship between oxidative stress and albuminuria could lead to discoveries of best pharmacological treatment of XO- and/or uric acid-induced ROS, in order to prevent albuminuria onset and progression.
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Affiliation(s)
- Aleksandra Klisic
- Center for Laboratory Diagnostics, Primary Health Care Center, Trg Nikole Kovacevica 6, 81000, Podgorica, Montenegro.
| | - Gordana Kocic
- Department of Medical Biochemistry, University of Nis - School of Medicine, Nis, Serbia
| | - Nebojsa Kavaric
- Center for Laboratory Diagnostics, Primary Health Care Center, Trg Nikole Kovacevica 6, 81000, Podgorica, Montenegro
| | - Milovan Jovanovic
- Center for Laboratory Diagnostics, Primary Health Care Center, Trg Nikole Kovacevica 6, 81000, Podgorica, Montenegro
| | | | - Ana Ninic
- Department of Medical Biochemistry, University of Belgrade - Faculty of Pharmacy, Belgrade, Serbia
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Ahmad KA, Yuan Yuan D, Nawaz W, Ze H, Zhuo CX, Talal B, Taleb A, Mais E, Qilong D. Antioxidant therapy for management of oxidative stress induced hypertension. Free Radic Res 2017; 51:428-438. [PMID: 28427291 DOI: 10.1080/10715762.2017.1322205] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hypertension is considered as the most common risk factor for cardiovascular diseases, also is regarded as a leading cause of the mortality and morbidity worldwide. The mechanisms underlying the pathological process of hypertension are not completely explained. However, there is growing evidence that increased oxidative stress plays an important role in the pathophysiology of hypertension. Several preclinical studies and clinical trials have indicated that antioxidant therapy is important for management of hypertension, using antioxidants compounds such as alpha tocopherol (Vit E) and ascorbic acid (Vit C), polyphenols with others and some antihypertensive drugs that are now in clinical use (e.g. ACEIs, ARBs, novel B-blockers, dihydropyridine CCBs) which have antioxidative pleiotropic effects. The purpose of this review is to highlight the importance of antioxidant therapy for management of oxidative stress induced hypertension. Furthermore, we review the current knowledge in the oxidative stress and its significance in hypertension.
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Affiliation(s)
- Khalil Ali Ahmad
- a Department of Pharmacology, School of Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Dai Yuan Yuan
- a Department of Pharmacology, School of Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Waqas Nawaz
- b School of Basic Medicine and Clinical Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Hong Ze
- a Department of Pharmacology, School of Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Chen Xue Zhuo
- a Department of Pharmacology, School of Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Bashar Talal
- c Department of Pharmacy Practice, JSS College of Pharmacy , JSS University , Mysuru , India
| | - Abdoh Taleb
- a Department of Pharmacology, School of Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Enos Mais
- d Department of Pharmacognosy, School of Pharmacy , China Pharmaceutical University , Nanjing , China
| | - Ding Qilong
- a Department of Pharmacology, School of Pharmacy , China Pharmaceutical University , Nanjing , China
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Electrophilic Nitro-Fatty Acids: Nitric Oxide and Nitrite-Derived Metabolic and Inflammatory Signaling Mediators. Nitric Oxide 2017. [DOI: 10.1016/b978-0-12-804273-1.00016-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Interplay between oxidant species and energy metabolism. Redox Biol 2015; 8:28-42. [PMID: 26741399 PMCID: PMC4710798 DOI: 10.1016/j.redox.2015.11.010] [Citation(s) in RCA: 217] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 11/20/2015] [Accepted: 11/25/2015] [Indexed: 02/07/2023] Open
Abstract
It has long been recognized that energy metabolism is linked to the production of reactive oxygen species (ROS) and critical enzymes allied to metabolic pathways can be affected by redox reactions. This interplay between energy metabolism and ROS becomes most apparent during the aging process and in the onset and progression of many age-related diseases (i.e. diabetes, metabolic syndrome, atherosclerosis, neurodegenerative diseases). As such, the capacity to identify metabolic pathways involved in ROS formation, as well as specific targets and oxidative modifications is crucial to our understanding of the molecular basis of age-related diseases and for the design of novel therapeutic strategies. Herein we review oxidant formation associated with the cell's energetic metabolism, key antioxidants involved in ROS detoxification, and the principal targets of oxidant species in metabolic routes and discuss their relevance in cell signaling and age-related diseases.
Energy metabolism is both a source and target of oxidant species. Reactive oxygen species are formed in redox reactions in catabolic pathways. Sensitive targets of oxidant species regulate the flux of metabolic pathways. Metabolic pathways and antioxidant systems are regulated coordinately.
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The Effects of Xanthine Oxidoreductase Inhibitors on Oxidative Stress Markers following Global Brain Ischemia Reperfusion Injury in C57BL/6 Mice. PLoS One 2015; 10:e0133980. [PMID: 26230326 PMCID: PMC4521791 DOI: 10.1371/journal.pone.0133980] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 07/05/2015] [Indexed: 02/07/2023] Open
Abstract
We demonstrated that 3-nitrotyrosine and 4-hydroxy-2-nonenal levels in mouse brain were elevated from 1 h until 8 h after global brain ischemia for 14 min induced with the 3-vessel occlusion model; this result indicates that ischemia reperfusion injury generated oxidative stress. Reactive oxygen species production was observed not only in the hippocampal region, but also in the cortical region. We further evaluated the neuroprotective effect of xanthine oxidoreductase inhibitors in the mouse 3-vessel occlusion model by analyzing changes in the expression of genes regulated by the transcription factor nuclear factor-kappa B (including pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 and intercellular adhesion molecules-1). Administration of allopurinol resulted in a statistically significant decrease in IL-1β and TNF-α mRNA expression, whereas febuxostat had no significant effect on expression of these genes; nevertheless, both inhibitors effectively reduced serum uric acid concentration. It is suggested that the neuroprotective effect of allopurinol is derived not from inhibition of reactive oxygen species production by xanthine oxidoreductase, but rather from a direct free-radical-scavenging effect.
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Akimoto T, Morishita Y, Ito C, Iimura O, Tsunematsu S, Watanabe Y, Kusano E, Nagata D. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease. Drug Target Insights 2014; 8:39-43. [PMID: 25210423 PMCID: PMC4134003 DOI: 10.4137/dti.s16524] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Revised: 06/27/2014] [Accepted: 07/01/2014] [Indexed: 02/07/2023] Open
Abstract
Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD.
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Affiliation(s)
- Tetsu Akimoto
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan. ; Green Town Clinic, Tochigi, Japan
| | - Yoshiyuki Morishita
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan. ; Kumakura Clinic, Tochigi, Japan. ; Yuki Clinic, Ibaraki, Japan
| | - Chiharu Ito
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan. ; Kumakura Clinic, Tochigi, Japan. ; Yuki Clinic, Ibaraki, Japan
| | | | | | - Yuko Watanabe
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
| | - Eiji Kusano
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
| | - Daisuke Nagata
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
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González J, Valls N, Brito R, Rodrigo R. Essential hypertension and oxidative stress: New insights. World J Cardiol 2014; 6:353-366. [PMID: 24976907 PMCID: PMC4072825 DOI: 10.4330/wjc.v6.i6.353] [Citation(s) in RCA: 143] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2013] [Revised: 03/01/2014] [Accepted: 05/08/2014] [Indexed: 02/06/2023] Open
Abstract
Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.
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Rodrigo R, González J. Role of Oxidative Stress in Hypertension. ROLE OF OXIDATIVE STRESS IN CHRONIC DISEASES 2014:199-245. [DOI: 10.1201/b16653-14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout. Rheumatol Int 2013; 34:101-9. [PMID: 24026528 DOI: 10.1007/s00296-013-2857-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Accepted: 08/30/2013] [Indexed: 01/19/2023]
Abstract
We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid-femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤ 360 μmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.
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Simão ANC, Lozovoy MAB, Dichi I. The uric acid metabolism pathway as a therapeutic target in hyperuricemia related to metabolic syndrome. Expert Opin Ther Targets 2012; 16:1175-87. [PMID: 23020656 DOI: 10.1517/14728222.2012.723694] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Uric acid (UA) increase is considered an important risk factor for the development of cardiovascular disease (CVD) favoring oxidative stress and endothelial dysfunction and is also involved in metabolic syndrome (MS) pathophysiology. AREAS COVERED Insulin has a physiological action on renal tubules, causing a reduction in UA clearance, what could explain the hyperuricemia found in MS. On the other hand, it was also hypothesized a causal role of UA in fructose-induced MS. Moreover, it has been suggested that higher UA levels predict the development of MS. MS subjects present a redox imbalance and UA participates in this process. UA can contribute to oxidative stress present in MS; however, it has also an important role in the antioxidant defense system. Although UA may have a protective effect due to its antioxidant properties, it is clear that the dominant effect of UA in MS is deleterious. All-cause mortality and CVD have been shown to be increased with higher UA levels. EXPERT OPINION It is extremely important to prescribe drugs which concomitantly decrease hyperuricemia and improve co-morbidities associated with hyperuricemia. Long-term studies to verify the consequences of decreasing UA concentration below current recommendations in asymptomatic patients are needed.
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Affiliation(s)
- Andréa Name Colado Simão
- Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Rua Robert Koch n. 60 Bairro Cervejaria, CEP: 86038-440, Brazil
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Murata M, Fukushima K, Takao T, Seki H, Takeda S, Wake N. Oxidative stress produced by xanthine oxidase induces apoptosis in human extravillous trophoblast cells. J Reprod Dev 2012; 59:7-13. [PMID: 22986926 PMCID: PMC3943235 DOI: 10.1262/jrd.2012-053] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Oxidative stress has been recognized as an important factor in the pathophysiology of
preeclampsia. It has been reported that the expression of xanthine oxidase (XO) in the
cytotrophoblast and plasma hydrogen peroxide (H2O2) level are
significantly higher in preeclamptics than in control women. The aim of this study was to
clarify the biological influence of reactive oxygen species (ROS) produced by XO on
extravillous trophoblast (EVT) cells. TCL1 cells, a human immortalized EVT cell line, were
incubated with xanthine and XO (X/XO). We then measured the cell number, urate level of
the culture media and the apoptotic cell ratio. Similar experiments were performed with
additional administration of allopurinol, catalase, L-NAME or D-NAME, and with
administration of H2O2 in substitution for X/XO. We assessed the
effects of H2O2 on invasion ability, tube-like formation and protein
expression of HIF1A and ITGAV of TCL1. Finally, the apoptotic cell ratio using primary
cultured trophoblasts was measured following exposure to H2O2. X/XO
decreased the relative cell number and increased the urate level and apoptotic cell ratio
significantly. Elevation of the urate level and apoptotic cell ratio was attenuated by
allopurinol and catalase, respectively. L-NAME and D-NAME had no influence on these
effects. H2O2 also decreased the relative cell number. Pretreatment
with H2O2 significantly inhibited the invasion ability, tube-like
formation and HIF1A and ITGAV of TCL1. H2O2 also induced apoptosis
in primary cultured trophoblasts. In conclusion, ROS produced by XO induced apoptosis and
affected EVT function including invasion and differentiation.
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Affiliation(s)
- Masaharu Murata
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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Chen Q, Park HC, Goligorsky MS, Chander P, Fischer SM, Gross SS. Untargeted plasma metabolite profiling reveals the broad systemic consequences of xanthine oxidoreductase inactivation in mice. PLoS One 2012; 7:e37149. [PMID: 22723833 PMCID: PMC3377762 DOI: 10.1371/journal.pone.0037149] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Accepted: 04/13/2012] [Indexed: 02/07/2023] Open
Abstract
A major challenge in systems biology is integration of molecular findings for individual enzyme activities into a cohesive high-level understanding of cellular metabolism and physiology/pathophysiology. However, meaningful prediction for how a perturbed enzyme activity will globally impact metabolism in a cell, tissue or intact organisms is precluded by multiple unknowns, including in vivo enzymatic rates, subcellular distribution and pathway interactions. To address this challenge, metabolomics offers the potential to simultaneously survey changes in thousands of structurally diverse metabolites within complex biological matrices. The present study assessed the capability of untargeted plasma metabolite profiling to discover systemic changes arising from inactivation of xanthine oxidoreductase (XOR), an enzyme that catalyzes the final steps in purine degradation. Using LC-MS coupled with a multivariate statistical data analysis platform, we confidently surveyed >3,700 plasma metabolites (50-1,000 Da) for differential expression in XOR wildtype vs. mice with inactivated XOR, arising from gene deletion or pharmacological inhibition. Results confirmed the predicted derangements in purine metabolism, but also revealed unanticipated perturbations in metabolism of pyrimidines, nicotinamides, tryptophan, phospholipids, Krebs and urea cycles, and revealed kidney dysfunction biomarkers. Histochemical studies confirmed and characterized kidney failure in xor-nullizygous mice. These findings provide new insight into XOR functions and demonstrate the power of untargeted metabolite profiling for systemic discovery of direct and indirect consequences of gene mutations and drug treatments.
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Affiliation(s)
- Qiuying Chen
- Department of Pharmacology, Weill Cornell Medical College, New York, New York, United States of America
| | - Hyeong-Cheon Park
- Departments of Medicine, Pathology and Pharmacology, Renal Research Institute, New York Medical College, Valhalla, New York, United States of America
| | - Michael S. Goligorsky
- Departments of Medicine, Pathology and Pharmacology, Renal Research Institute, New York Medical College, Valhalla, New York, United States of America
| | - Praveen Chander
- Departments of Medicine, Pathology and Pharmacology, Renal Research Institute, New York Medical College, Valhalla, New York, United States of America
| | - Steven M. Fischer
- Metabolomics Laboratory, Agilent Technologies, Santa Clara, California, United States of America
| | - Steven S. Gross
- Department of Pharmacology, Weill Cornell Medical College, New York, New York, United States of America
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Resl M, Clodi M, Neuhold S, Kromoser H, Riedl M, Vila G, Prager R, Pacher R, Strunk G, Luger A, Hülsmann M. Serum uric acid is related to cardiovascular events and correlates with N-terminal pro-B-type natriuretic peptide and albuminuria in patients with diabetes mellitus. Diabet Med 2012; 29:721-5. [PMID: 22050532 DOI: 10.1111/j.1464-5491.2011.03515.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes. METHODS In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded. RESULTS The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 μmol/l (range 101.1-743.5 μmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model. CONCLUSION Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.
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Affiliation(s)
- M Resl
- Department of Endocrinology, Medical University of Vienna, Vienna, Austria
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Vitoratos N, Vlahos NF, Economou E, Panoulis K, Creatsas G. Changes in maternal serum thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women. Hypertens Pregnancy 2011; 31:140-6. [PMID: 21250889 DOI: 10.3109/10641955.2010.544800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To investigate changes of maternal plasma thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women. METHODS Ten normotensive women (group A) were compared to 17 women with severe preeclampsia (group B). TRX levels were assessed in maternal plasma, immediately after delivery and 12-16 weeks postpartum. RESULTS There were no differences in plasma TRX levels between the two groups immediately antepartum (p = 0.095). A significant reduction in plasma TRX levels was found immediately following delivery only in normotensive group (117.76 ± 37.19 ng/mL vs. 43.45 ± 21.11 ng/mL, p = 0.002), but not in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 53.82 ± 44.34 ng/mL, p = 0.12). Plasma TRX levels remained unchanged in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 55.37 ± 52.23 ng/mL, p = 0.2) at 12-14 weeks postpartum.
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Affiliation(s)
- Nicolaos Vitoratos
- 2nd Department of Obstetrics and Gynecology, School of Medicine, University of Athens, Aretaieion Hospital, Athens, Greece
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Rodrigo R, González J, Paoletto F. The role of oxidative stress in the pathophysiology of hypertension. Hypertens Res 2011; 34:431-40. [PMID: 21228777 DOI: 10.1038/hr.2010.264] [Citation(s) in RCA: 284] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hypertension is considered to be the most important risk factor in the development of cardiovascular disease. An increasing body of evidence suggests that oxidative stress, which results in an excessive generation of reactive oxygen species (ROS), has a key role in the pathogenesis of hypertension. The modulation of the vasomotor system involves ROS as mediators of vasoconstriction induced by angiotensin II, endothelin-1 and urotensin-II, among others. The bioavailability of nitric oxide (NO), which is a major vasodilator, is highly dependent on the redox status. Under physiological conditions, low concentrations of intracellular ROS have an important role in the normal redox signaling maintaining vascular function and integrity. However, under pathophysiological conditions, increased levels of ROS contribute to vascular dysfunction and remodeling through oxidative damage. In human hypertension, an increase in the production of superoxide anions and hydrogen peroxide, a decrease in NO synthesis and a reduction in antioxidant bioavailability have been observed. In turn, antioxidants are reducing agents that can neutralize these oxidative and otherwise damaging biomolecules. The use of antioxidant vitamins, such as vitamins C and E, has gained considerable interest as protecting agents against vascular endothelial damage. Available data support the role of these vitamins as effective antioxidants that can counteract ROS effects. This review discusses the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of vascular damage in hypertension, and the possible therapeutic strategies that could prevent or treat this disorder.
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Affiliation(s)
- Ramón Rodrigo
- Renal Pathophysiology Laboratory, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
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