Eda Nur ALMALI, Kayihan KARACOR, Hakan SOYLU

Hidroksitirozolün Diyabetik Sıçan Karaciğerinde Prdx6 Ekspresyonu Üzerindeki Etkisi

Amaç: Diabetes mellitusun en önemli komplikasyonu olan hipergliseminin sebep olduğu oksidatif stres, karaciğer hasarına neden olmaktadır. Hidroksitirosol, zeytinyağında bol miktarda bulunan ve karaciğeri oksidatif hasara karşı da koruyan polifenolik bir bileşiktir. Peroksiredoksin 6 (Prdx6), karaciğerde varlığı bilinen bir anti-oksidatif enzimdir. Bu çalışmanın amacı, hidroksitirozolün diyabete bağlı karaciğer hasarındaki koruyucu rolünde Prdx6 ekspresyonunun etkisini araştırmaktı. Gereç ve Yöntemler: Erkek Wistar ratlar kontrol grubu (n=10), hidroksitirozol grubu (n=10), streptozotosin grubu (n=10) ve hidroksitirozol+streptozotosin grubu (n=10) olmak üzere dört gruba bölündü. Hayvanların kan glukoz seviyesi streptozotosin enjeksiyonu sonrasında ve deney sonunda da ölçüldü. Karaciğerin genel yapısı ise hematoksilen-eozin boyasıyla incelendi. Prdx6 proteinin ekspresyonu immunohistokimya yöntemi ile belirlendi. Bulgular: Streptozotosin+hidroksitirozol grubunda kan glukoz seviyesi streptozotosin grubu ile kıyaslandığında daha düşük olarak bulundu (p<0,001) ve hepatositlerdeki histopatolojik bulgularda ise azalma olduğu saptandı. Prdx6 ekspresyonu kontrol ve hidroksitirozol gruplarında benzer olarak bulundu (p=0,590). Ancak streptozotosin ve streptozotosin+hidroksitirozol gruplarında onlardan daha yüksek olduğu saptandı (p<0,001). Streptozotosin+hidroksitirozol grubu Prdx6 ekspresyonu streptozotosin grubuna göre daha düşük olarak bulundu (p<0,001). Sonuç: Birçok çalışmada antioksidatif etkinliği kanıtlanmış olan hidroksitirozol diyabetik ratlarda kan glukoz seviyesini düşürdüğü, hepatositlerdeki histopatolojik değişikliklere neden olduğu ve antioksidatif Prdx6 ekspresyonunu azalttığı bulunmuştur. Bu azalma bize, hidroksitirozolün doğrudan Prdx6’yı inhibe etmesinden ziyade, Prdx6’dan bağımsız bir şekilde oksidatif stresi azaltmasına bağlı olarak gerçekleşiyor olabileceğini düşündürdü.

Anahtar Kelimeler:

Diyabetes Mellitus, Karaciğer, Hidroksitirozol, Prdx6, Streptozotosin

Effect of Hydroxytyrosol on Prdx6 Expression in Diabetic Rat Liver

Aim: Oxidative stress caused by hyperglycemia, which is the most important complication of diabetes mellitus, causes liver damage. Hydroxytyrosol is a polyphenolic compound abundant in olive oil that protects the liver against oxidative damage. Peroxiredoxin 6 (Prdx6) is an anti-oxidative enzyme known to exist in the liver. The aim of this study was to investigate the effect of hydroxytyrosol on Prdx6 expression in diabetes-induced liver injury. Material and Methods: Male Wistar rats were grouped into four as the control group (n=10), hydroxytyrosol group (n=10), streptozotocin group (n=10), and hydroxytyrosol+streptozotocin group (n=10). Blood glucose levels of the animals were measured after streptozotocin injection and at the end of the experiment. The general structure of the liver was examined with a hematoxylin-eosin stain. Prdx6 protein expression was determined with an immunohistochemical method. Results: In the streptozotocin+hydroxytyrosol group, blood glucose level was found to be lower when compared with the streptozotocin group (p<0.001), and histopathological findings in hepatocytes were found to decrease. Prdx6 expression was found to be similar in the control and hydroxytyrosol groups (p=0.590). However, it was found to be higher in streptozotocin and streptozotocin+hydroxytyrosol groups (p<0.001). Prdx6 expression of the streptozotocin+hydroxytyrosol group was found lower than the streptozotocin group (p<0.001). Conclusion: Hydroxytyrosol, the anti-oxidative activity of which has been proven in many studies, was found to relieve blood glucose levels in diabetic rats, cause histopathological changes in hepatocytes, and decrease anti-oxidative Prdx6 expression. This decrease suggested that instead of inhibiting Prdx6, hydroxytyrosol reduced oxidative stress irrespective of Prdx6.

Keywords:

Diabetes Mellitus, Liver, Hydroxytyrosol, Streptozotocin, Prdx6,

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