Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat’ s Chest Irradiation

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Yahyapour Rasoul; AMINI PEYMAN; SAFFAR HANA; Rezapoor Saeed; MOTEVASELI ELAHE; Cheki Mohsen; FARHOOD BAGHER; Nouruzi Farzad; Shabeeb Dheyauldeen; Eleojo Musa Ahmed; NAJAFI MASOUD

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Journal: International Journal of Molecular and Cellular Medicine Year:2018 | Volume:7 | Issue:3 Page(s): 193-202

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Title

Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat’ s Chest Irradiation

Author(s)

Keywords

Radiation

Metformin

Heart Injury

IL-4

IL-13;DUOX1

DUOX2

Abstract

Radiation-induced heart toxicity is one of the serious side effects after a Radiation disaster or radiotherapy for patients with chest cancers, leading to a reduction in the quality of life of the patients. Evidence has shown that infiltration of inflammatory cells plays a key role in the development of functional damages to the heart via chronic upregulation of some pro-fibrotic and pro-inflammatory cytokines. These changes are associated with continuous free radical production and increased stiffness of heart muscle. IL-4 and IL-13 are two important pro-fibrotic cytokines which contribute to the side effects of ionizing Radiation exposure. Recent studies have proposed that IL-4 through upregulation of DUOX2, and IL-13 via stimulation of DUOX1 gene expression, are involved in the development of Radiation late effects. In the present study, we aimed to detect changes in the expression of these pathways following irRadiation of rat’ s heart. Furthermore, we evaluated the possible protective effect of Metformin on the development of these abnormal changes. 20 male rats were divided into 4 groups (control, Radiation, Metformin treated, Metformin + Radiation). These rats were irradiated with 15 Gy 60Co gamma rays, and sacrificed after 10 weeks for evaluation of the changes in the expression of IL4R1, IL-13R2a, DUOX1 and DUOX2. In addition, the levels of IL-4 and IL-13 cytokines, as well as infiltration of macrophages and lymphocytes were detected. Results showed an upregulation of both DUOX1 and DUOX2 pathways in the presence of Metformin, while the level of IL-13 did not show any significant change. This was associated with infiltration of macrophages and lymphocytes. Also, treatment with Metformin could significantly attenuate accumulation of inflammatory cells, and upregulate these pathways. Therefore, suppression of dual oxidase genes by Metformin may be a contributory factor to its protective effect.

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APA: Copy

Yahyapour, Rasoul, AMINI, PEYMAN, SAFFAR, HANA, Rezapoor, Saeed, MOTEVASELI, ELAHE, Cheki, Mohsen, FARHOOD, BAGHER, Nouruzi, Farzad, Shabeeb, Dheyauldeen, & NAJAFI, MASOUD. (2018). Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat’ s Chest Irradiation. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE, 7(3), 193-202. SID. https://sid.ir/paper/332233/en

Vancouver: Copy

Yahyapour Rasoul, AMINI PEYMAN, SAFFAR HANA, Rezapoor Saeed, MOTEVASELI ELAHE, Cheki Mohsen, FARHOOD BAGHER, Nouruzi Farzad, Shabeeb Dheyauldeen, NAJAFI MASOUD. Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat’ s Chest Irradiation. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE[Internet]. 2018;7(3):193-202. Available from: https://sid.ir/paper/332233/en

IEEE: Copy

Rasoul Yahyapour, PEYMAN AMINI, HANA SAFFAR, Saeed Rezapoor, ELAHE MOTEVASELI, Mohsen Cheki, BAGHER FARHOOD, Farzad Nouruzi, Dheyauldeen Shabeeb, and MASOUD NAJAFI, “Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat’ s Chest Irradiation,” INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE, vol. 7, no. 3, pp. 193–202, 2018, [Online]. Available: https://sid.ir/paper/332233/en

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