The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats

Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.