The role of Sildenafil and Bacillus clausii for the Prevention of Methotrexate Induced Mucositis: A Preclinical Study

Abstract

Objective: Methotrexate (MTX) is a commonly used chemotherapeutic agent in clinical oncology practice and in treatment of autoimmune diseases. The major side effect during treatment is mucositis. Recently published studies reported that this effect may be due to direct intestinal epithelial injury and disturbance of intestinal microbiota. In this study, we aimed to characterize the intestinal histological changes caused by MTX and to investigate the effects and safety of Sildenafil and probiotic Bacillus clausii on intestinal mucositis in a rat model. Materials and Methods: The rats were divided in 4 groups; Group1(n=8) received MTX + B. clausii, Group 2 (n=8) received only MTX, Group3 (n=8) received MTX + Sildenafil and Group 4 (n=7) was served as control (received no treatment). Results: The rate of villus atrophy, villous fusion and erosion in the MTX + B. clausii group were found to be statistically significantly lower than in the MTX group and the MTX + Sildenafil group. Conclusion: The study demonstrated the effect of B. clausii on repairing of intestinal mucosa after MTX-treatment. The better understanding of the effects of probiotics on intestinal mucosal protection may lead to new therapeutic approaches in chemotherapy-induced mucositis.

Keywords

• Bacillus clausii
• methotrexate
• probiotic
• rat
• sildenafil

Sildenafil ve Bacillus Clausii’nin Metotreksat Bağlı Mukozitin Önlenmesindeki Rolü: Preklinik Çalışma

Öz

Amaç: Metotreksat (MTX), klinik onkoloji pratiğinde ve otoimmün hastalıkların tedavisinde yaygın olarak kullanılan bir kemoterapötik ajanıdır. Tedavi sırasındaki ana yan etkisi mukozittir. Son zamanlarda yayınlanan çalışmalar, bu etkinin doğrudan bağırsak epiteli hasarına ve bağırsak mikrobiyotasının bozulmasına bağlı olabileceğini bildirmiştir. Bu çalışmada, MTX'ın neden olduğu bağırsak histolojik değişikliklerini karakterize etmeyi ve bir sıçan modelinde Sildenafil’ in ve probiyotik Bacillus clausii’ nin bağırsak mukozit üzerindeki etkilerini ve güvenliğini araştırmayı hedefledik. Materyal ve Metot: Sıçanlar 4 gruba ayrıldı; Grup 1 (n=8) MTX + B. clausii aldı, Grup 2 (n=8) sadece MTX aldı, Grup 3 (n=8) MTX + Sildenafil aldı ve Grup 4 (n=7) kontrol olarak kullanıldı (tedavi almadı). Bulgular: MTX + B.clausii grubunda villüs atrofisi, villöz füzyon ve erozyon oranı, MTX grubu ve MTX + Sildenafil grubuna göre istatistiksel olarak anlamlı derecede düşük bulundu. Sonuç: Çalışma, MTX tedavisinden sonra B. clausii ‘nin bağırsak mukozasının onarımı üzerindeki etkisini gösterdi. Probiyotiklerin intestinal mukozal koruma üzerindeki etkilerinin daha iyi anlaşılması, kemoterapiye bağlı mukozitte yeni terapötik yaklaşımlara yol açabilir.

Anahtar Kelimeler

• Bacillus clausii
• metotreksat
• probiyotik
• sıçan
• sildenafil

Kaynakça

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