The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

Abstract

Objective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration. Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT), irradiation alone (RT), intraperitoneal amifostine plus irradiation (IPAMI), and intrarectal amifostine plus irradiation (IRAMI). The rats in the RT, IPAMI and IRAMI groups were irradiated individually with a single dose of 17.5 Gy to the pelvis. Amifostine was administered by the intraperitoneal (200 mg/kg) or intrarectal (2000 mg/kg) route before irradiation. Histopathologic analysis of the rectum was performed 14 days after irradiation. Results: Significant radiation damage appeared in all histopathologic parameters and was reduced by amifostine. Pretreatment with IPAMI significantly reduced the inflammatory infiltrate in the lamina propria (p=0.021), cryptitis (p=0.002) and crypt abscess (p=0.015). However, the protective effect of IRAMI was significant for all parameters with equal or higher significance than IPAMI, including the eosinophil leucocytes count (p=0.02), and distortion of the crypts (p=0.008), and was also significant for regenerative/reparative atypia (p=0.013). Conclusion: Intrarectal high dose topical administration of amifostine is more effective in the prevention of radiation-induced proctitis compared to its intraperitoneal systemic administration. Turkish Başlık: Radyasyon Kaynaklı Proktitte Amifostinin Koruyucu Etkinliği: Sistemik İle Topikal Uygulamaların Karşılaştırılması Anahtar Kelimeler: Amifostin, proktit, ışınlama, radyoproteksiyon Amaç: Bu çalışmanın amacı ışınlama ile oluşturulan proktitte amifostinin radyoprotektif etkinliğinin intrarektal ve intraperitoneal uygulama yapılarak karşılaştırılmasıdır. Hastalar ve Yöntemler: Otuz iki Sprague-Dawley sıçan randomize olarak 4 gruba ayrıldı: Kontrol (CONT), sadece ışınlama (RT), intraperitoneal amifostin ve ışınlama (IPAMI) ile intrarektal amifostin ve ışınlama (IRAMI). RT, IPAMI ve IRAMI gruplarındaki sıçanların her birinin pelvis bölgesi tek fraksiyonda 17,5 Gy ışınlandı. Amifostin ışınlamadan önce intraperitoneal (200 mg/kg) veya intrarektal (2000 mg/kg) yoldan uygulandı. Rektumun histopatolojik incelemesi ışınlamadan 14 gün sonra yapıldı. Bulgular: Bütün histopatolojik parametrelerde ışınlamanın istatistiksel olarak anlamlı hasar oluşturduğu ve bu hasarın amifostin uygulaması ile azaldığı gözlendi. Işınlamadan önce IPAMI uygulaması lamina propria inflamasyonunu (p=0.021), kriptiti (p=0.002), kript absesini (p=0.015) anlamlı olarak azalttı. Buna karşın IRAMI ile koruyucu etki eozinofil lökosit sayısı (p=0.02), kript distorsiyonu (p=0.013) ve rejeneratif/reperatif atipi (p=0.013) dahil tüm parametreler için anlamlı oldu ve anlamlılıkları IPAMI'ya göre eşit veya daha yüksekti. Sonuç: Amifostinin yüksek doz intrarektal topikal uygulaması ışınlamanın oluşturduğu proktitin önlenmesinde intraperitoneal sistemik uygulamasına göre daha etkindir. Anahtar sözcükler: Amifostin, proktit, ışınlama, radyoproteksiyon.

Keywords

• Amifostine, proctitis, irradiation, radioprotection

The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

Öz

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