Radyasyona bağlı akut pulmoner toksisitede Dimetil Sülfoksit'in koruyucu etkisinin 99mTc--dietilentriaminpentaasetik asit transalveoler klirens sintigrafisi ve histopatoloji ile araştırılması
Yükleniyor...
Dosyalar
Tarih
2009
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Toraks bölgesine uygulanan radyoterapide akciğerin radyosensitvitesi doz kısıtlayıcıdır. Radyasyonun akciğerde oluşturduğu hasarın erken dönemde tanınması, hastanın normal doku sensitivite profiline göre tedavi rejiminin kişiselleştirilmesini sağlar. Radyasyona bağlı akciğer hasarının gelişiminde serbest oksijen radikalleri başrolü oynar. Bu radikalleri bağlayarak ortamdan çeken radyoprotektör özellikli farmakolojik ajanlardan dimetil sülfoksit literatürde ilgi çekici araştırma konulardandır. Çalışmamızda tavşanlarda dimetil sülfoksitin erken dönem radyasyona bağlı akciğer hasarında koruyucu etkisinin değerlendirilmesi amaçlanmıştır. Denekler kontrol, radyoterapi, dimetil sülfoksit ardından radyoterapi ve yalnızca dimetil sülfoksit şeklinde gruplandırılmıştır. Radyoterapi planlanan gruplarda sağ hemitoraksa tek fraksiyonda 20 Gy radyoterapi uygulanmıştır. Dimetil sülfoksit ve dimetil sülfoksit ardından radyoterapi grubuna, ışınlamadan 30 dk önce 4.5 gr/kg %99 dimetil sülfoksit, intraperitoneal yoldan verilmiştir. Ondört günlük izlem sonunda 99mTeknesyum dietilentriaminpentaasetik asit klirens sintigrafileri çekilmiş, sakrifikasyon sonrası histopatolojik inceleme yapılmıştır. Sintigrafik incelemede ışınlama öncesi dimetil sülfoksit uygulanması, radyoterapi grubuna göre klirens yarılanma zamanında istatistiksel olarak anlamlı uzamaya neden olmuştur (p<0.026). Histopatolojik incelemede ışınlamadan önce dimetil sülfoksit uygulanmasıyla, radyoterapi grubuna göre radyasyona bağlı hasar bulgularında, azalma tespit edilmiş olup, alveoler eksuda da istatistiksel olarak anlamlı, peribronşiyal inflamasyonda ise eğilim gözlenmiştir. Yapılan terminal dUTP yapışkan uç işaretleme yöntemi testinde dimetil sülfksit uygulanmasının ışınlama ile aktive olan apoptozu belirgin olarak azalttığı ve bu azalmanın istatistiksel olarak anlamlı olduğu saptanmıştır (p=0018). Radyoterapi öncesi dimetil sülfoksit uygulanmasının radyoterapiye bağlı akciğer hasarında koruyucu etkisinin olabileceği ve bu konuda yeni çalışmaların yapılması gerekliliği sonucuna varılmıştır.
Abstract
The radiosensitivity of the lung is a dose-limiting factor in thoracic irradiation. Early prediction of radiation-induced lung injury is important to customize treatment regimen for each individual according to patient?s normal tissue sensitivity profile. Radical oxygen species have a pivotal role in radiation-induced lung injury. Radioprotective agent dimethyl sulfoxide, which scavenges these species, is an interesting issue in the literature. The aim of this study is to evaluate the radioprotective effect of dimethyl sulfoxide in acute phase of radiation-induced lung injury on an animal model. The rabbits were grouped as control, radiation-alone, dimethyl sulfoxide plus radiation, and dimethyl sulfoxide-alone. Right hemithoraxes of radiation-alone and dimethyl sulfoxide plus radiation groups were irradiated by single dose of 20Gy gamma radiation. Thiry minutes prior to irradiation, 99% dimethyl sulfoxide was applied to dimethyl sulfoxide plus radiation and dimethyl sulfoxide-alone groups at a dose of 4.5gr/kg, ip. After 14 days follow-up, 99mTechnetium diethyleneaminepentaacetic acid lung clearance scintigraphy was performed. Following sacrification, tissue specimens were assessed histopathologically. On scintigraphic assessment, dimethyl sulfoxide application prior to irradiation prolonged the diethyleneaminepentaacetic acid clearance time in dimethyl sulfoxide plus radiation group when compared to radiation-alone group at a statistically significant level (p<0.026). Histopathologic evaluation revealed a decrease in the severity of radiation-induced lung injury. In dimethyl sulfoxide plus radiation group, when compared to radiation-alone group. The decrease in alveolar edema was statistically significant, and there was a trend in peribronchial inflammatory cell infiltration. Terminal dUTP nick end labeling index showed a markedly decrease in dimethyl sulfoxide plus irradiation group, when compared to radiation-alone group and this decrease was found to be statistically significant (p=0.018). The results of our study suggest that dimethyl sulfoxide appears to be a protective agent against radiation-induced lung injury. Additional work is needed to better identify the effectiveness of dimethyl sulfoxide as radioprotective agent in radiation associated lung injury.
Abstract
The radiosensitivity of the lung is a dose-limiting factor in thoracic irradiation. Early prediction of radiation-induced lung injury is important to customize treatment regimen for each individual according to patient?s normal tissue sensitivity profile. Radical oxygen species have a pivotal role in radiation-induced lung injury. Radioprotective agent dimethyl sulfoxide, which scavenges these species, is an interesting issue in the literature. The aim of this study is to evaluate the radioprotective effect of dimethyl sulfoxide in acute phase of radiation-induced lung injury on an animal model. The rabbits were grouped as control, radiation-alone, dimethyl sulfoxide plus radiation, and dimethyl sulfoxide-alone. Right hemithoraxes of radiation-alone and dimethyl sulfoxide plus radiation groups were irradiated by single dose of 20Gy gamma radiation. Thiry minutes prior to irradiation, 99% dimethyl sulfoxide was applied to dimethyl sulfoxide plus radiation and dimethyl sulfoxide-alone groups at a dose of 4.5gr/kg, ip. After 14 days follow-up, 99mTechnetium diethyleneaminepentaacetic acid lung clearance scintigraphy was performed. Following sacrification, tissue specimens were assessed histopathologically. On scintigraphic assessment, dimethyl sulfoxide application prior to irradiation prolonged the diethyleneaminepentaacetic acid clearance time in dimethyl sulfoxide plus radiation group when compared to radiation-alone group at a statistically significant level (p<0.026). Histopathologic evaluation revealed a decrease in the severity of radiation-induced lung injury. In dimethyl sulfoxide plus radiation group, when compared to radiation-alone group. The decrease in alveolar edema was statistically significant, and there was a trend in peribronchial inflammatory cell infiltration. Terminal dUTP nick end labeling index showed a markedly decrease in dimethyl sulfoxide plus irradiation group, when compared to radiation-alone group and this decrease was found to be statistically significant (p=0.018). The results of our study suggest that dimethyl sulfoxide appears to be a protective agent against radiation-induced lung injury. Additional work is needed to better identify the effectiveness of dimethyl sulfoxide as radioprotective agent in radiation associated lung injury.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
Dimetil Sülfoksit, Radyoprotektif Ajan, Radyasyona Bağlı Akut Akciğer Hasarı, Dimethyl Sulfoxide, Radioprotective Agent, Radiation-Induced Lung Injury
