Assessment Of The Protective Effect Of Amifostine On Radiation Induced Pulmonary Injury

Objects: The protective effect of amifostine and mechanisms of regulating cytokines'activities were assessd on radiation-induced pulmonary injury. Further pathogenesis of radiation-induced pulmonary injury was investigated to give suggests to amifostine's clinical use.Metheods: 50 male Balb/c mice weight 18～20g were randomized into 4 groups, respectively 5 to 10 mouse per group, to receive (1) radiation alone; (2) radiation+amifostine; (3) amifostine alone; (4) sham radiation. Amifostine (200 mg/kg) had been given intraperitoneally 15 minutes before radiation.The total chest was given 12Gy once by 6 MV X-ray. Body weight and breathing rate were recorded weekly or every two weeks. During the posttreatment period ,animals in respiratory distress were sacrificed.Otherwise ,they were sacrificed at half month, first month, third month. Left lungs were used for Masson's trichrome stain of collagen and immunohistologic test of cytokine TGF-β1,TNF-α; the right lungs were used for Annexin V (FITC) /PI for apoptosis detection by flow cytometry.Results: Hair in the radiation field had been lost since 21 days after radiation in group radiation alone, some of which had skin rash,two days ealier than radiation+amifostine group. The width and length in radiation +amifostine group were smaller than radiation alone ,and no rash was found. The absolute value of weight increase was higher in radiation+amifostine group than radiation alone at third month (P＜0.05) ,and no difference was found at other time points .In Masson's trichrome stain, extensive collagen deposition was shown at third month in radiation alone.The alveolar wall lost its normal structure and became more thicker.But at the same time , mild collagen deposited in radiation+amifostine with some red blood cells and inflammatory fluids in the wall. The expression of TGF-β1 and TNF-αincreased after irradiation in comparison to sham radiation mice,demonstrating significant difference between groups of radiation+amifostine and radiation alone at any time points in immunohistological test (P＜0.05) . The early phase apoptosis rate of lung tissues in flow cytometry showed significant difference at early phase of pulmonary injury between radiation alone and radiation+amifostine (P＜0.05) ,but at other time points it revealed no difference. Apoptosis rate was lower in sham radiation than radiation alone(P＜0.05).Conclusions : Amifostine can protect the skin in the radiation field ,delay radiation lung fibrosis's happening and ameliorate the degree of ingury.Besides, it can cut down the expreesion of cytokine TNF-αand TGF-β1 in lung tissues after irradiation. The apoptosis rate decreased only during the early phase after the using of amifostine before irradiation. The predominant localization of TGF-β1and TNF-αin areas of inflammatory cell infiltrates and fibrosis suggests involvement of these cytokines in the pathogenesis of radiation-induced pulmonary injury.