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      Gum Arabic as novel anti-oxidant agent in sickle cell anemia, phase II trial

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          Abstract

          Background

          Sickle cell anemia patients suffer from oxidative stress due to chronic inflammation and self-oxidation of sickle hemoglobin (Hb S). Chronic oxidative stress contributes to endothelial dysfunction, inflammation and multiple organ damage in sickle cell disease (SCD). Thus, antioxidant medication may favorably influence the disease. Gum Arabic (GA), edible, dried, gummy exudates from Acacia Senegal tree, has been claimed to act as an anti-oxidant and cytoprotective agent, protecting against experimental hepatic, renal and cardiac toxicities in rats. We hypothesized that regular intake of GA increases anti-oxidant capacity and reduce oxidative stress.

          Methods

          Forty-seven patients (5–42 years) carrying hemoglobin SS were recruited. Patients received 30 g/day GA for 12 weeks. Total anti-oxidant capacity (TAC), malondialdehyde (MDA) and hydrogen peroxide (H 2O 2) levels were measured by spectrophotometric methods before and after GA intake. Complete blood count was measured by sysmex.

          Results

          Gum Arabic significantly increased TAC level P < 0.001and decreased the oxidative markers MDA ( P < 0.05) and H 2O 2 ( P < 0.005).

          Conclusions

          GA has potent anti- oxidative properties in sickle cell anemia. The anti-oxidant effect of GA may thus favorably influence the clinical condition of this and further diseases characterized by oxidative stress.

          Trial registration

          ClinicalTrials.gov Identifier: NCT02467257. Registered 3rd June 2015. Retrospective registration.

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          Most cited references31

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          Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method.

          K Satoh (1978)
          A new colorimetric method for quantitative analysis of serum lipid peroxide, free of interference from sialic acids, has been developed. We have used the thiobarbituric acid dissolved in sodium sulfate solution and both liberation of lipid peroxide and color reaction have been performed simultaneously by heating serum protein precipitate with this reagent in a weak acid solution. The new method is specific and facilitates the precise measurements of serum lipid peroxide. The average values determined by the new method increased slightly with age in healthy subjects. In patients with sequelae of cerebrovascular disorders, serum lipid peroxide values were higher than in healthy controls. These results may demonstrate the important role of lipid peroxide in aging and cerebrovascular disorders.
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            Role of oxidative stress in the pathogenesis of sickle cell disease.

            Sickle cell disease (SCD) is a class of hemoglobinopathy in humans, which causes a disruption of the normal activities in different systems. Although this disease begins with the polymerization of red blood cells during its deoxygenating phase, it can erupt into a cascade of debilitating conditions such as ischemia-reperfusion injury, inflammation, and painful vaso-occlusion crises. The purpose of this review is to discuss how these phenomena can result in the formation of oxidative stress as well as limit nitric oxide (NO) bioavailability and decrease antioxidant status. The cumulative effects of these traits cause an increase in other forms of reactive oxygen species (ROS), which in turn intensify the symptoms of SCD and generate a vicious circle. Finally, we will discuss antioxidant therapeutic strategies that limit ROS generation and subsequently increase NO bioavailability with respect to endothelial protection in SCD. Copyright © 2011 Wiley Periodicals, Inc.
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              Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease.

              Chronic inflammation has emerged as an important pathogenic mechanism in sickle cell disease (SCD). One component of this inflammatory response is oxidant stress mediated by reactive oxygen species (ROS) generated by leukocytes, endothelial cells, plasma enzymes, and sickle red blood cells (RBC). Sickle RBC ROS generation has been attributed to sickle hemoglobin auto-oxidation and Fenton chemistry reactions catalyzed by denatured heme moieties bound to the RBC membrane. In this study, we demonstrate that a significant part of ROS production in sickle cells is mediated enzymatically by NADPH oxidase, which is regulated by protein kinase C, Rac GTPase, and intracellular Ca(2+) signaling within the sickle RBC. Moreover, plasma from patients with SCD and isolated cytokines, such as transforming growth factor β1 and endothelin-1, enhance RBC NADPH oxidase activity and increase ROS generation. ROS-mediated damage to RBC membrane components is known to contribute to erythrocyte rigidity and fragility in SCD. Erythrocyte ROS generation, hemolysis, vaso-occlusion, and the inflammatory response to tissue damage may therefore act in a positive-feedback loop to drive the pathophysiology of sickle cell disease. These findings suggest a novel pathogenic mechanism in SCD and may offer new therapeutic targets to counteract inflammation and RBC rigidity and fragility in SCD.
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                Author and article information

                Contributors
                +2499129797 , lamiskaddam@hotmail.com
                imad@fadl-elmula.com
                aamheisawi@gmail.com
                habdelhakam1@hotmail.com
                halfa88@uofk.edu
                florian.lang@uni-tuebingen.de
                amalsaeed@yahoo.com
                Journal
                BMC Hematol
                BMC Hematol
                BMC Hematology
                BioMed Central (London )
                2052-1839
                16 March 2017
                16 March 2017
                2017
                : 17
                : 4
                Affiliations
                [1 ]Department of Physiology, Faculty of Medicine, Alneelain University, P.O. Box: 11121, Khartoum, 12702 Sudan
                [2 ]Alneelain Research Centre Faculty of Medicine, Alneelain University, Khartoum, Sudan
                [3 ]Department of Hematology Military Hospital, Khartoum, Sudan
                [4 ]Department of Pediatrics Military Hospital, Khartoum, Sudan
                [5 ]ISNI 0000 0001 0674 6207, GRID grid.9763.b, Department of Biochemistry, Faculty of Medicine, , University of Khartoum, ; Khartoum, Sudan
                [6 ]ISNI 0000 0001 2190 1447, GRID grid.10392.39, Department of Physiology, , University of Tübingen, ; Tübingen, Germany
                [7 ]ISNI 0000 0001 0674 6207, GRID grid.9763.b, Department of Physiology, Faculty of Medicine, , University of Khartoum, ; Khartoum, Sudan
                Author information
                http://orcid.org/0000-0002-1083-4514
                Article
                75
                10.1186/s12878-017-0075-y
                5356407
                28331623
                4d4aab71-08b5-4a0d-a335-c6eba135af80
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 October 2016
                : 7 March 2017
                Funding
                Funded by: Alneelain University
                Funded by: Higher Education and Scientific Research Mi(SD)
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                gum arabic,sickle,anti-oxidant,oxidative stress
                gum arabic, sickle, anti-oxidant, oxidative stress

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