Inhaled amifostine for the prevention of radiation-induced lung injury

Abstract

ObjectiveTo alleviate radiation-induced lung injury and prevent the related pneumonitis and pulmonary fibrosis by inhaled amifostine (AMI). Methods15 ​Gy 60Co γ-ray irradiation was performed on the thoracic area of rats once to establish the radiation injury model. AMI was intraperitoneally (i.p.) injected or intratracheally (i.t.) administered to the rats 30 ​min pre-irradiation. The protective effects of the two AMI administration manners were compared in the aspects of hematopoietic system, lung edema, and histopathological examination, and the mechanisms were explored. ResultsCompared to i.p. AMI, i.t. AMI remarkably alleviated radiation-induced lung injury and prevented consequent pneumonitis or pulmonary fibrosis. Specifically, i.t. AMI notably protected white blood cells and platelets, reduced the lung wet/dry weight ratio, and decreased collagen volume fractions compared to the model group (P ​< ​0.05), while i.p. AMI showed no significant difference with the model group (P ​> ​0.05). The high therapeutic efficiency of i.t. AMI was related to its high antioxidation and anti-inflammation effects with downregulation of pro-inflammatory cytokines, the enhanced superoxide dismutase activity, the low levels of malondialdehyde and total proteins. ConclusionInhaled AMI is a promising medicine for preventing radiation-induced lung injury, including pneumonitis and pulmonary fibrosis.