Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study

Abstract

Background and objectives: Pneumonitis and fibrosis are the most common consequences of lung exposure to a high dose of ionizing radiation during an accidental radiological or nuclear event, and may lead to death, after some months to years. So far, some anti-inflammatory and antioxidant agents have been used for mitigation of lung injury. In the present study, we aimed to detect possible mitigatory effects of melatonin and metformin on radiation-induced pneumonitis and lung fibrosis. Materials and methods: 40 male mice were divided into 4 groups (10 mice in each). For control group, mice did not receive radiation or drugs. In group 2, mice were irradiated to chest area with 18 Gy gamma rays. In groups 3 and 4, mice were first irradiated similar to group 2. After 24 h, treatment with melatonin as well as metformin began. Mice were sacrificed after 100 days for determination of mitigation of lung pneumonitis and fibrosis by melatonin or metformin. Results: Results showed that both melatonin and metformin are able to mitigate pneumonitis and fibrosis markers such as infiltration of inflammatory cells, edema, vascular and alveolar thickening, as well as collagen deposition. Conclusion: Melatonin and metformin may have some interesting properties for mitigation of radiation pneumonitis and fibrosis after an accidental radiation event.

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment

“…Besides, melatonin caused a decrease in interstitial tissue percentage volume and an increase in the alveolar space percentage volume [55]. Melatonin attenuated the pneumonitis and lung fibrosis caused by radiation exposure through a decrease in inflammatory cell infiltration, collagen deposition, edema, and vascular and alveolar thickening in the lungs [56]. Idiopathic pulmonary fibrosis causes the progressive loss of pulmonary function due to tissue cicatrization.…”

Attenuation of Radiation-Induced Lung Injury by Hyaluronic Acid Nanoparticles

“…In their study, Johnston et al, (2004) suggested that neutrophils do not participate in RIPI devolvement within the mouse model. Other reports, however, have confirmed the infiltration of neutrophils during early time intervals after irradiation (Österreicher et al, 2004;Abernathy et al, 2015;Farhood et al, 2019). Neutrophils are the innate immune system's effector cells recruited earliest to the site of pathology.…”

Pineal hormone melatonin as an adjuvant treatment for COVID‑19 (Review)

“…Melatonin could act by prohibiting pulmonary fibrosis in a rat animal model, due to minimizing chloride channel activity, which was mediated by protein kinase C ( 42 ). In another study, melatonin modulated pneumonitis and lung fibrosis, caused by exposure to radiation by decreasing inflammatory cell infiltration, collagen deposition and alveolar thickening in the lungs ( 43 ). It is noteworthy, that melatonin and its metabolites could regulate the appropriate pro-fibrogenic and pro-inflammatory signaling pathways, which are involved in the pathophysiology of pulmonary fibrosis, leading to its protective effects on the lungs ( 44 ).…”