Metformin Protects against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression

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

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Journal: Advanced Pharmaceutical Bulletin Year:2018 | Volume:8 | Issue:4 Page(s): 697-704

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Title

Metformin Protects against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression

Author(s)

Keywords

Radiation

Metformin

Inflammation

Fibrosis

DUOX1

DUOX2

Abstract

Purpose: Lung tissue is one of the most sensitive organs to ionizing Radiation (IR). Early and late side effects of exposure to IR can limit the Radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and Fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and Fibrosis. Metformin is a potent anti-Fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of Metformin in these cytokines and genes, as well as histopathological changes in rat’ s lung tissues. Methods: 20 rats were divided into 4 groups: control; Metformin treated; Radiation + Metformin; and Radiation. IrRadiation was performed with a 60Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Results: IrRadiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, Fibrosis, as well as vascular and alveolar damages. Treatment with Metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Conclusion: Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and DUOX2, while that of IL-13 decreased. Treatment with Metformin showed ability to attenuate upregulation of IL-4– DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.

Cites

Selenium-L-methionine modulates radiation injury and Duox1 and Duox2 upregulation in rat’ s heart tissues

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APA: Copy

Azmoonfar, Rasoul, AMINI, PEYMAN, SAFFAR, HANA, Rezapoor, Saeed, MOTEVASELI, ELAHE, Cheki, Mohsen, Yahyapour, Rasoul, FARHOOD, BAGHER, Nouruzi, Farzad, Khodamoradi, Ehsan, Shabeeb, Dheyauldeen, Musa, Ahmed Eleojo, & NAJAFI, MASOUD. (2018). Metformin Protects against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression. ADVANCED PHARMACEUTICAL BULLETIN, 8(4), 697-704. SID. https://sid.ir/paper/740082/en

Vancouver: Copy

Azmoonfar Rasoul, AMINI PEYMAN, SAFFAR HANA, Rezapoor Saeed, MOTEVASELI ELAHE, Cheki Mohsen, Yahyapour Rasoul, FARHOOD BAGHER, Nouruzi Farzad, Khodamoradi Ehsan, Shabeeb Dheyauldeen, Musa Ahmed Eleojo, NAJAFI MASOUD. Metformin Protects against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression. ADVANCED PHARMACEUTICAL BULLETIN[Internet]. 2018;8(4):697-704. Available from: https://sid.ir/paper/740082/en

IEEE: Copy

Rasoul Azmoonfar, PEYMAN AMINI, HANA SAFFAR, Saeed Rezapoor, ELAHE MOTEVASELI, Mohsen Cheki, Rasoul Yahyapour, BAGHER FARHOOD, Farzad Nouruzi, Ehsan Khodamoradi, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, and MASOUD NAJAFI, “Metformin Protects against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression,” ADVANCED PHARMACEUTICAL BULLETIN, vol. 8, no. 4, pp. 697–704, 2018, [Online]. Available: https://sid.ir/paper/740082/en

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