The Effect Of Amifostine On Radiation-induced Lung Injury And TGFβ1 Level In Mice

Objective To investigate the effect of Amifostine on lung and TGFβ1 level using the mouse model with radiation-induced lung injury.Methods 80 female C57/BL mice were randomly divided into four groups: 32 amifostine plus radiation, 32 radiation alone, 8 amifostine alone and 8 control groups. The whole lung of mice was irradiated by a singe dose of 12Gy. In the first group, Amifostine(200mg/kg) had been given intraperitoneally 30 minutes before irradiation. Two or eight mice of each group were sacrificed respectively on week 4, 8, 12,and 24. TGFβ1 level in serum was obtained, as well as the lung samples of light microscopy and electron microscopy. Hematoxylin and eosin (H&E) stain and Van Gieson stain were performed on the lung tissue slices to observe changes in microstructure.Results 1,RT-induced pneumonitis at early eight weeks was typified by congestion, infiltration of inflammatory cells and thickening of the alveolar septa. Following the acute phase of damage, there were reduction of inflammatory cells and progressive fibrosis of alveolar septa, which were prominent in peribronchial and perivascular areas. Irradiated mice treated with amifostine showed a reduction in the extent of lung damage,with less collagen deposition, as compare to radiation alone. 2,Electron microscopy at 8 and 12 weeks revealed prominent increase of type II pneumocytes and lamellar body, some of which were vague and vacuolated. Type II pneumocytes and lamellar body decrease greatly 24 weeks after RT, with prominent basement membrane thickening and increased collagen deposition. Ultramicrostructural changes of mice treated with amifostine were not notable as compare to radiation alone. 3,The TGFβ1 levels in serum showed an increase after radiation, peaking at 8 weeks in the mice with amifostine and peaking at 12 weeks in those without amifostine. The TGFβ1 levels 4 and 8 weeks after RT were significantly higher in the amifostine plus radiation group(21.6361±6.53517ng/ml and 35.9464±6.35279ng/ml) than in mice given radiation alone (0.4303±0.09438ng/ml and 12.2099± 6.19280ng/ml)(P=0.014 and P=0.018,respectively). TGFβ1 levels were significantly lower at 12 and 24 weeks in mice receiving amifostine plus radiation(0.7184±0.19457ng/ml and 3.1672±2.89109ng/ml)versus those receiving radiation alone(29.7173±11.22294ng/ml and 7.4864±3.70193ng/ml)(P=0.036 and P=0.009, respectively).Conclusion 1,It is a long period in which acute toxicity gradually changes to chronic toxicity. 2,This study confirms the protective effect of amifostine in reducing radiation-induced pulmonary toxicity. 3,The increase of TGFβ1 levels in the mice with amifostine appear earlier than those without amifostine, and then decrease rapidly. Further observation and discussion are needed.