The protective effect of sildenafil on liver sinusoidal obstructive syndrome after oxaliplatin-based chemotherapy: An experimental animal study

Abstract

Aim: Sinusoidal obstructive syndrome (SOS) that develops due to oxaliplatin-based chemotherapy influences morbidity and mortality following surgical treatment of colorectal liver metastases. The aim of this study was to evaluate the protective effect of sildenafil on liver damage (sinusoidal obstructive syndrome (SOS)) that develops due to oxaliplatin-based chemotherapy.
Methods: An experimental animal study was conducted and a total of 42 rats were randomly separated into 4 groups as Sham, intraperitoneal chemotherapy (ipCT), ipCT+low-dose sildenafil treatment, and ipCT +high-dose sildenafil treatment. The ipCT was applied once a week for 5 weeks. Histochemical analysis was made in the livers removed from rats.
Results: Parenchymal, stromal, and vascular changes were examined, and no statistically significant difference was determined between the groups with respect to the severity of sinusoidal dilatation (P=0.243). The groups significantly differed with regards to centrilobular, peliotic changes and hepatocellular changes (P<0.001).
Conclusion: Sildenafil has a protective effect against liver damage that develops due to oxaliplatin-based chemotherapy and prevents the development of SOS during chemotherapy in colorectal cancer patients. Therefore, it could be considered as a treatment strategy.

Keywords

• Oxaliplatin
• Sinusoidal obstructive syndrome
• Sildenafil
• Colorectal cancer
• Liver metastasis

Sildenafil'in oksaliplatin esaslı kemoterapi sonrası karaciğerde gelişen sinüsoidal obstruktif sendrom üzerine koruyucu etkisi: Deneysel bir hayvan çalışması

Öz

Amaç: Oksaliplatin bazlı kemoterapinin karaciğer metastazlı kolon kanserli hastalarda kullanımı karaciğer hasarına (sinüsoidal obstruktif sendrom (SOS)) neden olarak; metastaz rezeksiyonu sonrasında mortalite ve morbiditeyi arttırır. Bu çalışmamızda; sildenafilin kolorektal kanserlerin karaciğer metastazları için oksaliplatin bazlı kemoterapi sonucunda gelişen karaciğer hasarı, (SOS) üzerindeki koruyucu etkisini değerlendirmeyi amaçladık.
Yöntemler: Deneysel bir hayvan çalışması yürütüldü ve toplam 42 rat rastgele Sham, intraperitoneal kemoterapi (ipCT), ipCT + düşük doz sildenafil tedavisi ve ipCT +yüksek doz sildenafil tedavi grupları olarak 4 gruba ayrıldı. İpCT, 5 haftalık bir süre boyunca haftada birkez uygulandı. Ratlardan çıkarılan karaciğerlerde histopatolojik analiz yapıldı.
Bulgular: Parankimal, stromal ve vasküler değişiklikler incelendi ve sinüzoidal dilatasyonun şiddeti açısından gruplar arasında istatistiksel olarak anlamlı bir fark bulunmadı (P=0,243). Dört grup arasında sentrolobüler değişiklikler açısından istatistiksel olarak anlamlı fark saptandı (P<0,001). Peliotik ve hepatosellüler değişikliklerin değerlendirilmesinde gruplar arasındaki fark istatistiksel olarak anlamlı bulundu (P<0,001).
Sonuç: Sildenafil, kolorektal kanser hastalarında kemoterapi sırasında oksaliplatin bazlı kemoterapinin bir sonucu olarak gelişen SOS gelişimini önleyerek karaciğer hasarına karşı koruyucu bir etkiye sahip olması nedeniyle, kemoterapi esnasında tedaviye eklenmelidir.

Anahtar Kelimeler

• Oxaliplatin
• Sinüsoidal obstrüktif sendrom
• Sildenafil
• Kolorektal kanser
• Karaciğer metastaz

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