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      Irisin Protects Against Hind Limb Ischemia Reperfusion Injury

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          Abstract

          Aim

          The aim of this study was to evaluate the effects of irisin in a murine model of hind limb ischemia reperfusion (I/R).

          Methods

          The mice were divided into four groups (n = 6 in each group): control, irisin, ischemia reperfusion (I/R), and irisin-ischemia reperfusion (I–I/R). Irisin (0.5 µg.g −1, intraperitoneally [i.p.]) was administered 30 min before the I/R procedure. After 2 h of ischemia and 2.5 h of reperfusion, blood and tissue samples were taken for biochemical and histopathological analysis. The results were analyzed by Kruskal–Wallis and Mann–Whitney U-tests.

          Results

          There was a statistically significant difference in the total antioxidant status (TAS) and total oxidant status (TOS) levels in all the groups. The TAS level in the I/R group was significantly lower than that in the control, irisin, and I–I/R groups, whereas the TOS level was significantly higher in the I/R group as compared with that in the other groups. Caspase-3 activity and caspase-8 activity, indicators of inflammation, were significantly higher in the I/R and I–I/R groups as compared with those in the control and irisin groups.

          Conclusion

          Irisin may have protective effects in skeletal muscle ischemia reperfusion injury.

          Most cited references34

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          A PGC1α-dependent myokine that drives browning of white fat and thermogenesis

          Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be a protein therapeutic for human metabolic disease and other disorders that are improved with exercise.
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            Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.

            Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α, and Pgc1a(-/-) mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Free Radicals in Biology and Medicine

              "This latest edition has been comprehensively rewritten and updated (over 80% of the text is new), whilst 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 ageing 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." "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 medical sciences."--BOOK JACKET.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                04 February 2021
                2021
                : 15
                : 361-368
                Affiliations
                [1 ]Kutahya Health Sciences University , Medical Faculty, Department of Physiology, Kutahya, Turkey
                [2 ]Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital , Department of Cardiovascular Surgery, Istanbul, Turkey
                [3 ]Yildirim Beyazit University , Medical Faculty, Department of Pathology, Ankara, Turkey
                [4 ]Gulhane Medical Faculty, Gulhane Education and Research Hospital , Department of Cardiovascular Surgery, Ankara, Turkey
                [5 ]Atilim University , Medical Faculty, Department of Physiology, Ankara, Turkey
                [6 ]Gazi University , Medical Faculty, Department of Anesthesiology and Reanimation, Ankara, Turkey
                Author notes
                Correspondence: Mustafa Arslan Gazi University, Medical Faculty, Department of Anesthesiology and Reanimation , Ankara, 06510, TurkeyTel +90 312 202 67 39 Email mustarslan@gmail.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-9316-9574
                http://orcid.org/0000-0002-7981-4458
                http://orcid.org/0000-0002-3733-7198
                http://orcid.org/0000-0001-9056-0025
                http://orcid.org/0000-0003-4882-5063
                Article
                279318
                10.2147/DDDT.S279318
                7871175
                566bc4bb-d40c-4259-a800-3086df533a29
                © 2021 Küçük et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 02 September 2020
                : 18 January 2021
                Page count
                Figures: 6, Tables: 2, References: 34, Pages: 8
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                irisin,ischemia reperfusion,caspase-3,caspase-8,mice
                Pharmacology & Pharmaceutical medicine
                irisin, ischemia reperfusion, caspase-3, caspase-8, mice

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