Amifostine Protects Small Bowel Against Radiation-induced Apopitosis by Reducing Caspase-3

Abstract

Objective: The aim of the study was to investigate the protective effect of amifostine against radiotherapy-induced small bowel injury.

Materials and Methods: Forty rats were divided equally into four groups as control, irradiation (IR), IR + Amifostine, IR+N-acetyl cysteine (NAC) groups. Caspase-3 expression, villus lengths, and microscopic tissue injury were evaluated histopathologically. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) and malondialdehyde (MDA) were measured biochemically in jejunum tissue. Pre- and post-radiation weights of the rats were recorded.

Results: Caspase-3 was at the highest level in the IR group, at the lowest level in the control and weak in the Amifostine+IR group. The lowest microscopic score was determined in the IR group and the difference between the groups was statistically significant. CAT decreases after IR. However, Amifostine and NAC prevented radiation-induced catalase decline. In Amifostine+IR group, the villus length was significantly longer than that of the IR group. Amifostine was observed to protect against weight loss.

Conclusion: The results obtained from this study demonstrate that the administration of Amifostine can substantially reduce apopitosis and support the repair of the structure and function of intestinal tissues which have been damaged by exposure to radiation. These results also suggest that it may be a promising therapeutic agent.

Keywords

• Amifostine; Apoptosis; Caspase-3; Oxidative stress; Radiotherapy.

Amifostin İnce Bağırsakları Kaspaz-3’ü Azaltarak Radyasyonun İndüklediği Apopitozise Karşı Korur

Abstract

Amaç: Bu çalışmanın amacı, amifostinin radyoterapiye bağlı ince bağırsak hasarına karşı koruyucu etkisini araştırmaktır.

Materyal ve Metod: Kırk rat, kontrol, radyasyon (IR), IR + Amifostin, IR + N-asetil sistein (NAC) grupları olmak üzere dört gruba eşit olarak ayrıldı. Kaspaz-3 ekspresyonu, villus uzunlukları ve mikroskobik doku hasarı histopatolojik olarak değerlendirildi. Jejunum dokusunda süperoksit dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GPx), miyeloperoksidaz (MPO) ve malondialdehid (MDA) biyokimyasal olarak ölçüldü. Ratların radyasyon öncesi ve sonrası ağırlıkları kaydedildi.

Bulgular: Kaspaz-3, IR grubunda en yüksek düzeyde, kontrol grubunda en düşük düzeyde ve Amifostin + IR grubunda zayıftı. En düşük mikroskopik skor IR grubunda belirlendi ve gruplar arasındaki fark istatistiksel olarak anlamlıydı. CAT, IR'den sonra azalmıştı. Bununla birlikte, Amifostin ve NAC radyasyon kaynaklı katalaz düşüşünü önledi. Amifostin + IR grubunda, villus uzunluğu, IR grubundan anlamlı derecede daha uzundu. Amifostinin kilo kaybına karşı korunduğu gözlendi.

Sonuç: Bu çalışmadan elde edilen sonuçlar, Amifostin uygulamasının apopitozu büyük ölçüde azaltabildiğini ve radyasyona maruziyetten zarar gören bağırsak dokularının yapısını ve işlevini onardığını desteklemektedir. Bu sonuçlar Amifostinin ümit verici bir terapötik ajan olabileceğini düşündürmektedir.

Keywords

• Amifostin; Apopitoz; Kaspaz-3; Oksidatif stress; Radyoterapi

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