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- Volume 20, Issue 37, 2013
Current Medicinal Chemistry - Volume 20, Issue 37, 2013
Volume 20, Issue 37, 2013
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Oxidative Stress and Amyloid Beta Toxicity in Alzheimer’s Disease: Intervention in a Complex Relationship by Antioxidants
Authors: S. Chakrabarti, M. Sinha, I. G. Thakurta, P. Banerjee and M. ChattopadhyayThe elucidation of the intriguing relationship between oxidative stress and Alzheimer’s disease is crucial to understand the pathogenesis of the disease as also to design a suitable drug trial with antioxidants against this condition. We begin by reviewing the basic facts about Alzheimer’s disease and the chemistry and biology of oxygen free radicals with particular reference to the cellular adaptive response through redox-signalling pathways. The post-mortem evidence of oxidative damage in the brain of Alzheimer’s disease patients is overwhelming which is also supported by the similar changes in transgenic mice models of this disease. However, the causal relationship of oxidative stress with amyloid beta pathology or the genesis of Alzheimer’s disease is not clear. Considering the available evidence the review suggests that the oxidative stress could be an early event in the disease process and may trigger various adaptive responses such as the alterations of amyloid beta metabolism and the activation of stress responsive kinases which can subsequently lead to neuronal degeneration and AD pathology. Further, we have presented a large body of evidence from various studies to highlight the beneficial effects of antioxidants against amyloid beta toxicity or AD pathology in animal or cell based models of AD. The failure of clinical trials with antioxidants against AD has been mentioned and the possible causes of such failures have been analysed.
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Interaction of Anthocyanins with Drug-metabolizing and Antioxidant Enzymes
Authors: H. Bartikova, L. Skalova, J. Drsata and I. BousovaAnthocyanins are generally considered to be the largest and the most important group of water-soluble pigments in plants. They are widely consumed by humans as natural compounds of vegetables, fruits, and red wine. Anthocyanins as well as other flavonoids show protective qualities against variety of pathologies, including cardiovascular diseases, cancer, diabetes mellitus, neurodegeneration, inflammation, viral infections, and obesity. Many healthy properties of anthocyanins are related to their antioxidant potency. Broad evidence of beneficial effects of anthocyanins on human health has led to their increasing popularity in the form of food supplements and nutraceuticals. As the nutraceuticals contain concentrated bioactive agents, consumed doses exceed those that could be obtained from food. Therefore, apart from anticipated improvement of human health it is essential to have in mind possible unexpected effects of anthocyanins. Interaction of these compounds with drug-metabolizing enzymes and transporters may affect the fate of co-administered drugs and thus exert pharmacological consequences. On the other hand, the modulation of certain drug-metabolizing and antioxidant enzymes by anthocyanins can contribute to chemoprotection and antioxidant defense of organisms. The present review summarizes anthocyanin properties with emphasis on the antioxidant capacity and deals with the potential of anthocyanins to modulate phase I and II drug-metabolizing enzymes, transporters and antioxidant enzymes. The undesirable and/or beneficial outcomes of possible interactions of anthocyanins with drugs or industrial pollutants are also discussed.
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Potential Impact of Genetic Variants in Nrf2 Regulated Antioxidant Genes and Risk Prediction of Diabetes and Associated Cardiac Complications
Authors: T. Ramprasath and G. S. SelvamThe prevalence, incidence and mortality of all cardiovascular disorders (CVD) are two- to eightfold higher in persons with diabetes than in those without diabetes. Predicting and understanding the causes of CVD still represents an enormous challenge for clinical and basic cardiovascular science. Similarly, the fundamental mechanism by which diabetic patients are more prone to heart failure is unclear and prevention of such cardiac risk remains a major challenge for which new strategies are needed. Imbalance between free radicals and anti-oxidant defenses is associated with cellular dysfunctions leading to the pathophysiology of various diseases. Evidence suggests that diabetes is associated with a reduced overall antioxidant defense system and the increased oxidative stress. This may contribute to the pathogenesis of the diabetic complications, notably the emergence of premature atherosclerosis. The transcription factor NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) regulates the expression of many detoxifying genes such as catalase, superoxide dismutase, UDP-glucuronosyltransferase, c-glutamylcysteine synthetase, NAD(P)H quinone oxidoreductase 1, glutathione- S-transferase, glutathione peroxidase-1 and heme oxygenase-1. Polymorphic effects of these antioxidant genes and their regulatory regions have higher relevancy to the susceptibility to clinical conditions such as diabetes, obesity and cardiovascular diseases. Thus, the present review aims to explore the relationship between free radicals, diabetes and its associated complications with respect to the genetic makeup of Nrf2/ARE regulated genes in an effort to expand treatment options.
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The Use of Flavonoids in Central Nervous System Disorders
Authors: C. Grosso, P. Valentao, F. Ferreres and P. B. AndradeNeurodegenerative, neurological and psychiatric diseases are a group of pathologies with huge social and economic impacts. Since brain disorders continue to be pathological conditions for which corrective surgery cannot be widely used, treatments are based on drugs that only alleviate the symptoms. Despite all efforts in finding more efficient therapeutic agents, the requirement for neuroprotective drugs able to cross the blood-brain barrier (BBB) has been a hard challenge to overcome. Flavonoids are known by their antioxidant activities thus preventing oxidative stress, which is believe to be one of the causes of disorders affecting the central nervous system. Moreover, they can also modulate both enzymes and receptors activities, being regarded as multi-target botanical therapeutics or drugs. This review will give emphasis to the benefits of flavonoids found in the diet in the treatment of Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, and schizophrenia. The antioxidant effect of several flavonoids, as well as their effects not related with antioxidant activity, in the above mentioned diseases will be reviewed. Aspects concerning structure-activity relationships, but also the bioavailability of these compounds in the brain will be referred.
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Advances in Antioxidative Therapy of Multiple Sclerosis
Authors: E. Miller, B. Wachowicz and I. MajsterekMultiple sclerosis (MS) is a chronic, multifactorial disease of the central nervous system (CNS), typified by repetitive relapses and/or progression. The conventional treatment options in MS are limited. However, recently several new drugs have been introduced. Oxidative stress is a crucial factor in MS pathogenesis by ameliorating leukocyte migration, contributing to oligodendrocyte damage and axonal injury. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are created in CNS of MS patients mainly by activated macrophages and microglia structures responsible for demyelinisation and axons disruption. Activated microglia secretes different inflammatory and oxidative stress mediators such as cytokines (TNF and IL- 1b and IL- 6) and chemokines (macrophage inflammatory protein MIP- 1a, monocyte chemoattractant protein, MCP- 1 and interferon (IFN) inducible protein IP- 10). The inflammatory state is promoted by that. MS in chronic stages is dominated by neurogenerative processes involving axon and neuron loss probably resulting from oxidative stress and excitotoxicity. Therefore, consideration of the treatment engaging antioxidants and diet supplementation is needed. The present review describes the antioxidative system in CNS and possible antioxidative therapies in MS. Although some exogenous compounds have been proposed as such approach to MS treatment, there is a strong need for further research in this field. Such investigation is required for better understanding of the potential of protective effects of antioxidants in cellular immunology of MS neurodegeneration. Not only would that increase our knowledge about the disease mechanisms but also could help to establish new goals for innovative treatment methods and provide real therapeutic benefits in MS.
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Electron Spin Resonance as a Powerful Tool for Studying Antioxidants and Radicals
Authors: G. Barriga-Gonzalez, B. Aguilera-Venegas, C. Folch-Cano, F. Perez-Cruz and C. Olea-AzarThe study of antioxidants and radicals has always been a complex task due to the special characteristics of these species such as reactions at low concentrations and short half–lives. Current techniques do not always produce good results and in some cases they can only be applied in chemical models. From this point of view, the development of electron spin resonance (ESR) has allowed the study of the antioxidant capacity of a wide variety of compounds and the detection of radicals in the reactions in which they are involved. The DPPH technique allows only the study of antioxidants in pure chemical models. The ORAC–ESR assay, based on the spin trapping technique, emerges as an interesting tool for identifying and quantifying the antioxidant capacity of different samples. Furthermore, the spin trapping technique allows us to characterize radicals in in vivo/ex vivo models. The present review discusses the current available techniques associated with ESR for the study of antioxidants and radical species.
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Drug-Delivery Systems of Green Tea Catechins for Improved Stability and Bioavailability
Authors: C. F. Rodrigues, K. Ascencao, F. A.M. Silva, B. Sarmento, M. B.P.P. Oliveira and J. C. AndradeNumerous studies in humans, animal models and cell lines have suggested the potential benefits from the consumption of green tea polyphenols, including prevention of cancer and heart diseases. However these potential effects have been strongly limited by green tea catechins low bioavailability, which hinders the development of therapeutic applications. In this review formulations that are being proposed for delivery of green tea catechins are discussed. New delivery systems are presented as valid alternatives to overcome the limitations such as green tea catechins poor stability or intestinal absorption.
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An Up-date of Olive Oil Phenols in Inflammation and Cancer: Molecular Mechanisms and Clinical Implications
Authors: A. Cardeno, M. Sanchez-Hidalgo and C. Alarcon-de-la-LastraOlive oil (OO), the main fatty component of the Mediterranean diet, exhibits numerous biological functions which are beneficial for the state of health. In addition to monounsaturated fatty acid (MUFA) evidences have accumulated on the favorable properties of its minor though highly bioactive components, particularly the phenolic compounds, which have shown a broad spectrum of bioactive properties, including antioxidant and anti-inflammatory effects both associated with the origin of the main chronic diseases. Additional studies have demonstrated that the health effects of olive oil polyphenols have been also associated with their, neuroprotective, antiaging and antiatherogenic effects. On the other hand, because of their ability to modulate cell death, olive polyphenols have been proposed as chemopreventive and therapeutic agents. Thus, the purpose of this article is to review the chemistry, bioavailability and pharmacokinetic characteristics of OO polyphenols, in addition to provide the reader an up-date of their putative antioxidant, anti-inflammatory and anti-cancer activities as well as the plausible action mechanisms involved.
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Counteracting Oxidative Stress in Pregnancy through Modulation of Maternal Micronutrients and Omega-3 Fatty Acids
Authors: V. D'Souza, P. Chavan-Gautam and S. JoshiDuring pregnancy, oxidative stress has been implicated in the pathophysiology of preeclampsia and preterm birth leading to poor birth outcome. Hyperhomocysteinemia caused as a consequence of altered micronutrients like folic acid and vitamin B12 is associated with increased production of reactive oxygen species that generate oxidative stress. These micronutrients are important determinants of methyl donor, s-adenosyl methionine while phospholipids are important methyl acceptors in the one-carbon metabolic cycle. A series of our studies in women during pregnancy have demonstrated altered levels of these micronutrients and the negative association of docosahexaenoic acid with homocysteine. Various strategies to counteract oxidative stress during pregnancy such as antioxidant therapy have been examined and found to be inconsistent. In this review, we focus on the role of oxidative stress in pregnancy and discuss the possibility of ameliorating it through modulation of maternal micronutrients and omega 3 fatty acids especially docosahexaenoic acid. We propose for the first time that manipulation of one-carbon metabolism by maternal diet could be a potential mechanism to counteract oxidative stress through homocysteine lowering effects and help in reducing the risk for adverse pregnancy outcomes.
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Bio-Antioxidants – A Chemical Base of Their Antioxidant Activity and Beneficial Effect on Human Health
Authors: V. D. Kancheva and O. T. KasaikinaThe paradox of aerobic life is that higher eukaryotic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. Autoxidation of organic substances frequently occurs via free radical mechanism which generates different active radicals and peroxides OH•, O2•-, LO2•, HOOH, LOOH, so called reactive oxygen species (ROS), which appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate - or obtain from food - a variety of water- and lipid-soluble antioxidant compounds. Biologically active compounds with antioxidant potential, i.e. bio-antioxidants (natural and their synthetic analogues) have a wide range of applications. They are important drugs, antibiotics, agrochemical substitutes, and food preservatives. Many of the drugs today are synthetic modifications of naturally obtained substances. This review presents information about the chemical base of antioxidant activities and beneficial effects on human health of known and new bio-antioxidants. There is abundant literature on the phenolic antioxidants and tocopherols in particular. In this review the following bio-antioxidants are considered: A) Carotenoids, B) Cathecholamines, C) Phospholipids, D) Chalcones, E) Coumarins, F) Phenolic acids, G) Flavonoids, H) Lignans, and I) Tannins.
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Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis
Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by endothelial dysfunction, and in which innate and adaptive immune responses have a crucial role. Autoimmune reactions against several self molecules and modified self molecules have been identified in patients with atherosclerotic disease. Oxidative stress, increasingly reported in these patients is the major event causing protein structural modifications, thus inducing the appearance of neo/cryptic epitopes. Following intraplaque haemorrhage large amounts of cell-free haemoglobin (Hb) accumulate within atheroma, due to its impaired clearance by the haptoglobin-CD163 scavenging system. The pro-oxidative intraplaque microenvironment may induce Hb structural changes, thus generating neo/cryptic autoantigenic epitopes and rendering the oxidized self molecule as a dangerous signal for both immune and endothelial cells. In this review, we will present the most relevant information on Hb as a candidate self antigen involved in the pathogenesis of atherosclerotic disease and on its ability to trigger signals that drive endothelial dysfunction and immune cell activation. On these grounds, we will also discuss how these new paradigms may lead to novel therapeutic targets for cardiovascular diseases.
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Volumes & issues
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Volume 31 (2024)
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Volume 30 (2023)
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Volume 29 (2022)
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Volume 28 (2021)
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Volume 27 (2020)
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Volume 26 (2019)
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Volume 25 (2018)
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Volume 24 (2017)
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Volume 23 (2016)
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Volume 22 (2015)
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Volume 21 (2014)
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Volume 20 (2013)
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Volume 19 (2012)
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Volume 18 (2011)
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Volume 17 (2010)
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Volume 16 (2009)
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Volume 15 (2008)
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Volume 14 (2007)
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Volume 13 (2006)
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Volume 12 (2005)
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Volume 11 (2004)
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Volume 10 (2003)
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Volume 9 (2002)
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Volume 8 (2001)
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Volume 7 (2000)