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

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 Baslik: Radyasyon Kaynakli Proktitte Amifostinin Koruyucu Etkinligi: Sistemik Ile Topikal Uygulamalarin Karsilastirilmasi Anahtar Kelimeler: Amifostin, proktit, isinlama, radyoproteksiyon Amac: Bu calismanin amaci isinlama ile olusturulan proktitte amifostinin radyoprotektif etkinliginin intrarektal ve intraperitoneal uygulama yapilarak karsilastirilmasidir. Hastalar ve Yontemler: Otuz iki Sprague-Dawley sican randomize olarak 4 gruba ayrildi: Kontrol (CONT), sadece isinlama (RT), intraperitoneal amifostin ve isinlama (IPAMI) ile intrarektal amifostin ve isinlama (IRAMI). RT, IPAMI ve IRAMI gruplarindaki sicanlarin her birinin pelvis bolgesi tek fraksiyonda 17,5 Gy isinlandi. Amifostin isinlamadan once intraperitoneal (200 mg/kg) veya intrarektal (2000 mg/kg) yoldan uygulandi. Rektumun histopatolojik incelemesi isinlamadan 14 gun sonra yapildi. Bulgular: Butun histopatolojik parametrelerde isinlamanin istatistiksel olarak anlamli hasar olusturdugu ve bu hasarin amifostin uygulamasi ile azaldigi gozlendi. Isinlamadan once IPAMI uygulamasi lamina propria inflamasyonunu (p=0.021), kriptiti (p=0.002), kript absesini (p=0.015) anlamli olarak azaltti. Buna karsin IRAMI ile koruyucu etki eozinofil lokosit sayisi (p=0.02), kript distorsiyonu (p=0.013) ve rejeneratif/reperatif atipi (p=0.013) dahil tum parametreler icin anlamli oldu ve anlamliliklari IPAMI'ya gore esit veya daha yuksekti. Sonuc: Amifostinin yuksek doz intrarektal topikal uygulamasi isinlamanin olusturdugu proktitin onlenmesinde intraperitoneal sistemik uygulamasina gore daha etkindir. Anahtar sozcukler: Amifostin, proktit, isinlama, radyoproteksiyon.