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Current Drug Research Reviews

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ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

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Research Article

Protective Effect of Metformin, Resveratrol and Alpha-lipoic Acid on Radiation- Induced Pneumonitis and Fibrosis: A Histopathological Study

Author(s): Rasoul Yahyapour, Peyman Amini, Hana Saffar, Elahe Motevaseli, Bagher Farhood, Vahid Pooladvand, Dheyauldeen Shabeeb, Ahmed Eleojo Musa and Masoud Najafi*

Volume 11, Issue 2, 2019

Page: [111 - 117] Pages: 7

DOI: 10.2174/2589977511666191018180758

Abstract

Background: Radiation-induced pneumonitis and fibrosis are the most common side effects of chest radiotherapy. They result from massive and chronic production of Reactive Oxygen Species (ROS), inhibition of antioxidant enzymes as well as the release of several inflammatory mediators. In this study, we aimed to detect the radioprotective effects of metformin (as inhibitor of mitochondrial ROS), resveratrol (as stimulator of antioxidant defense enzymes) and alpha-lipoic acid (as direct antioxidant) for alleviating radiation-induced pneumonitis and fibrosis.

Methods: 80 Male Mice were randomly allotted to eight groups which include G1: control; G2: resveratrol; G3: alpha-lipoic acid; G4: metformin; G5: radiation; G6: radiation plus resveratrol; G7: radiation plus alpha-lipoic acid; G8: radiation plus metformin. Drugs’ doses were as follows: 100 mg/kg metformin, 200 mg/kg resveratrol and 200 mg/kg alpha-lipoic acid. Irradiation with a single radiation dose of 18 Gy was performed using a cobalt-60 (60Co) gamma-ray source. After 80 days, all mice were sacrificed and their lung tissues evaluated for morphological changes using histopathological markers.

Results: Irradiation led to acute pneumonitis including infiltration of inflammatory cells and damages to alveolar and vascular, as well as mild fibrosis. Metformin, alpha-lipoic acid and resveratrol were able to reduce pneumonitis and overcome radiation-induced fibrosis.

Conclusion: All agents could protect against radiation-induced lung injury moderately. It is possible that administering higher doses of these drugs over a long period of time could give better radioprotection of the lung.

Keywords: Radiation, lung, fibrosis, metformin, alpha-lipoic acid, resveratrol.

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