Radiation-induced lung toxicity is the principal dose limiting factor in the delivery of adequate levels of radiation to eradicate primary and metastatic lesions of the thorax and chest wall. This injury not only leads to significant sequelae but
also
increases the risk of late complication often causing the radiotherapist to limit the total dose delivered. Therefore, to prevent or decrease the risk of radiation-indeced lung injury, many trials had been performed. Of these trials,
pentoxifylline
as a
pharmacological agent that improves blood flow through small capillaries has generate widespread interest in the oncologic community based on its reported potential ability to ameliorate radiation and chemotherpay-induced toxicities. As an
extension of
those researches, this study was designed to evaluate the therapeutic effectiveness of PTX on the acute and late radiation-induced pulmonary injury in mice.
One hundred and twenty ICR mice of about 20-25g in the body weight were divided into three study groups : control, radiation alone, and radiation-pentoxifylline. Each group was subdivided into 12 subgroups: 1, 3, 6, and 10 days and 2, 3, 4, 6, 8,
12,
16, 20 weeks by observation period after irradiation. The total 1500cGy of radiation was delivered in a single fraction through a single anterior protal encompassing the entire thorax. The pentoxifylline was injected subcutaneously daily 50mg/Kg
to
the
back of the mice from the first day of irradiation throughout the observation period. The mice of each groups after a certain observation period wer sacrificed and were measured with white blood cell count and sectioned for evaluation by
histopathologic
changes using light- and electron microscopies. At 1-10 days there were swelling of endothelial cells, capillary congestion and periarterial infiltration of inflammatory cells, suggesting typical posirradiation pulmonary damage. The findings of
acute
pneumonitis appeared at 4-6 weeks : diffuse endothelial cell swelling and degeneration and proleferation of foamy macrophages, severe infiltration of inflammatory cells and swelling in the alveolar septa, changes of lamellar body and
proliferation
of
the type II pneumocytes. At 12-20 weeks, appearance of fibroblast, thickening of alveolar septa, diffuse deposition of dense collagen, and thickening of basal lamina were observed. the entire process of pathologic changes of
radiation-pentoxifylline
group was similar to those of radiation alone group but the severity of injury was much milder in both acute and late stages of pulmonary toxicity and damaging process was delayed compared with radiation alone group. Also it was noted that the
findings
of acute stage was relatively rapidly resolved compared with those of radiation alone group.
In conclusion, pentoxifyllne can effectively reduce the acute pulmonary injury as well as late stage of radiation-induced pulmonary injury and it also delays the entire process of pulmonary changes.
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