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      Oxidative Stress in Malaria

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          Abstract

          Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy.

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          Free Radicals in Biology and Medicine

          Barry Halliwell, John M. C. Gutteridge (2007)
          Free Radicals in Biology and Medicine has become a classic text in the field of free radical and antioxidant research since its first publication in 1985. <br> This latest edition has been comprehensively rewritten and updated (over 80% of the text is new), while maintaining the clarity of its predecessor. There is expanded coverage of isoprostanes and related compounds, mechanisms of oxidative damage to DNA and proteins (and the repair of such damage), the free radical theory of aging and the roles played by reactive species in signal transduction, cell death, human reproduction, and other important biological events. Greater emphasis has also been placed on the methods available to measure reactive species and oxidative damage (and their potential pitfalls), as well as the importance of antioxidants in the human diet. <br> This book is recommended as a comprehensive introduction to the field for students, clinicians and researchers, and an invaluable companion to all those interested in the role of free radicals in the life and biomedical sciences.
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            Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.

            J Beckman, W. Koppenol (1996)
            Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.
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              Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions.

              Katja Becker, Leann Tilley, Jonathan L Vennerstrom … (2004)
              Experimenta naturae, like the glucose-6-phosphate dehydrogenase deficiency, indicate that malaria parasites are highly susceptible to alterations in the redox equilibrium. This offers a great potential for the development of urgently required novel chemotherapeutic strategies. However, the relationship between the redox status of malarial parasites and that of their host is complex. In this review article we summarise the presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development. As delineated below, alterations in redox status contribute to disease manifestation including sequestration, cerebral pathology, anaemia, respiratory distress, and placental malaria. Studying haemoglobinopathies, like thalassemias and sickle cell disease, and other red cell defects that provide protection against malaria allows insights into this fine balance of redox interactions. The host immune response to malaria involves phagocytosis as well as the production of nitric oxide and oxygen radicals that form part of the host defence system and also contribute to the pathology of the disease. Haemoglobin degradation by the malarial parasite produces the redox active by-products, free haem and H(2)O(2), conferring oxidative insult on the host cell. However, the parasite also supplies antioxidant moieties to the host and possesses an efficient enzymatic antioxidant defence system including glutathione- and thioredoxin-dependent proteins. Mechanistic and structural work on these enzymes might provide a basis for targeting the parasite. Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: Molecular Diversity Preservation International (MDPI)
                ISSN (Electronic): 1422-0067
                Publication date Collection: 2012
                Publication date (Electronic): 03 December 2012
                Volume: 13
                Issue: 12
                Pages: 16346-16372
                Affiliations
                [1 ]Oxidative Stress Research Laboratory, Institute of Biological Sciences, Federal University of Para (LAPEO/ICB/UFPA) Av. Augusto Correa, 1, Guama, Belem, Para 66075-110, Brazil; E-Mails: alydan@ 123456hotmail.com (D.R.M.); brunoquadros@ 123456yahoo.com.br (B.A.Q.G.); mferreira@ 123456ufpa.br (M.E.S.F.); acmusa23@ 123456yahoo.com.br (A.C.M.G.); paula.biomedica@ 123456gmail.com (P.S.O.C.L.); tc-vilhena@ 123456hotmail.com (T.C.V.)
                [2 ]Pharmacy Faculty, Institute of Health Sciences, Federal University of Para. Av. Augusto Correa, 1, Guama, Belem, Para 66075-110, Brazil; E-Mail: fani@ 123456ufpa.br
                [3 ]US Centers for Disease Control and Prevention, 1600 Clifton Road NE, mailstop G49, Atlanta, GA 30329, USA; E-Mail: MGreen@ 123456cdc.gov
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: percario@ 123456ufpa.br or s.percario@ 123456bol.com.br ; Tel.: +55-91-8156-2289; Fax: +55-91-3201-7102.
                Article
                Publisher ID: ijms-13-16346
                DOI: 10.3390/ijms131216346
                PMC ID: 3546694
                PubMed ID: 23208374
                SO-VID: d27137af-8415-4931-97ee-d59ac9cd73b5
                Copyright © © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 17 October 2012
                Date revision received : 08 November 2012
                Date accepted : 23 November 2012
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: oxidative stress,malaria,free radicals,antioxidants,agaricus sylvaticus,nitric oxide
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: oxidative stress, malaria, free radicals, antioxidants, agaricus sylvaticus, nitric oxide

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