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
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.