Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Abstract

Radiation-induced lung injury (RILI) is commonly observed in patients receiving radiotherapy, and clinical prevention and treatment remain difficult. We investigated the effect and mechanism of nicaraven for mitigating RILI. C57BL/6 N mice (12-week-old) were treated daily with 6 Gy X-ray thoracic radiation for 5 days in sequences (cumulative dose of 30 Gy), and nicaraven (50 mg/kg) or placebo was injected intraperitoneally in 10 min after each radiation exposure. Mice were sacrificed and lung tissues were collected for experimental assessments at the next day (acute phase) or 100 days (chronic phase) after the last radiation exposure. Of the acute phase, immunohistochemical analysis of lung tissues showed that radiation significantly induced DNA damage of the lung cells, increased the number of Sca-1+ stem cells, and induced the recruitment of CD11c+, F4/80+ and CD206+ inflammatory cells. However, all these changes in the irradiated lungs were effectively mitigated by nicaraven administration. Western blot analysis showed that nicaraven administration effectively attenuated the radiation-induced upregulation of NF-κB, TGF-β, and pSmad2 in lungs. Of the chronic phase, nicaraven administration effectively attenuated the radiation-induced enhancement of α-SMA expression and collagen deposition in lungs. In conclusion we find that nicaraven can effectively mitigate RILI by downregulating NF-κB and TGF-β/pSmad2 pathways to suppress the inflammatory response in the irradiated lungs.