Ratlarda Dietilnitrozamin Uygulanarak Oluşturulan Oksidatif ve Nitrozatif Strese Karşı Silimarin’in Karaciğer Koruyucu Etkisi

Karaciğer kanseri dünyada kanserle ilişkili ölümlerde üçüncü sırada yer almaktadır. Hepatoselüler karsinom (HSK) primer karaciğer kanserlerinin %70-85’ini oluşturmaktadır. Bu çalışmada; deneysel karaciğer kanseri modelinde Dietilnitrozamin (DEN)'in rolünü araştırmayı ve silimarinin hepatoprotektif etkisini oksidatif-nitrozatif stres markerlerı kullanarak immunohistokimyasal yöntemlerle ayrıntılı olarak incelemeyi amaçladık. Bu amaçla 50 adet Wistar Albino cinsi erkek rat 10’arlı 5 gruba ayrıldı. DEN grubundaki hayvanlara 50 mg/kg dozunda haftada 1 kez deneme süresince DEN uygulaması yapıldı. DEN+silimarin grubundaki ratlara DEN uygulamasından 1 hafta önce başlayacak şekilde 100 mg/kg dozunda haftada 3 kez deneme süresince intraperitoneal yolla silimarin (propilen glikolde çözdürülmüş) uygulandı. Kontrol grubundaki ratlara deneme süresince pelet yem ve içme suyu verildi. Sham grubundaki hayvanlara % 0.9 NaCl içerisinde çözdürülmüş propilen glikol intraperitoneal yolla haftada 3 kez deneme süresince verildi. Silimarin grubundaki ratlara 100 mg/kg dozunda deneme süresince intraperitoneal yolla haftada 3 kez silimarin uygulandı. 21 haftanın sonunda DEN ve DEN+silimarin gruplarında makroskobik olarak farklı büyüklük ve boyutlarda nodüler yapılar tespit edildi. Mikroskobik incelemede nodüllerin HSK oldukları belirlendi. Sonuç olarak DEN’in karaciğer kanserini indüklediği; silimarinin ise iNOS ve Nitrotirozin ekspresyonları açısından istatistiksel olarak anlamlı bir koruyucu etki göstermediği belirlenmiştir.

Anahtar Kelimeler:

Dietilnitrozamin, hepatoselüler karsinom, nitrozatif stres, oksidatif stres, silimarin

Hepatoprotective Effect Of Silymarin Against Diethylnitrosamine Induced Oxidative-Nitrosative Stress in Rats

Liver cancer is the third most common cancer-related death in the World. Hepatocellular carcinoma (HCC) constitutes %70-85 of liver malignant primary tumors. In this study; we aimed to investigate the role of diethylnitrosamine (DEN) in the experimental liver cancer model and to examine the hepatoprotective effect of silymarin in detail using oxidative-nitrosative stress markers with immunohistochemical methods. For this purpose, 50 Wistar Albino male rats were divided into 5 groups with 10 rats. Animals in DEN group received DEN at a dose of 50 mg/kg once a week for 20 weeks. The rats in the DEN +Silymarin group were Silymarin intraperitoneally for 21 weeks 3 times a week at a dose of 100 mg/kg, starting 1 week prior to the administration of DEN. Silymarin was administered to rats in the group of Silymarin 3 times a week intraperitoneally for 20 weeks at a dose of 100 mg/kg. The rats in the control group were fed pellet feed and drinking water for 20 weeks. Animals in Sham group were treated with propylene glycol dissolved in 0,9 % NaCl intraperitoneally 3 times a week for 20 weeks. At the end of 21 weeks, macroscopically different size and number of nodular structures were detected in the DEN and DEN+Silymarin group. The microscopic examination revealed that the nodules were HCC. As a result, DEN induced liver cancer; however, silymarin did not show a statistically significant protective effect in terms of iNOS and Nitrotyrosine expressions.

Keywords:

diethylnitrosamine, hepatocellular carcinoma, nitrosative stress, oxidative stress, silymarin,

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