Sebile AZİRAK, Sedat BİLGİÇ, Deniz TAŞTEMİR KORKMAZ, Murat SEVİMLİ, Mehmet Kaya ÖZER

Timokinon’un sıçanların pankreas dokusunda valproik asidin neden olduğu hasarı iyileştirmeye etkisi

Amaç: Bu çalışmanın amacı timokinonun (TQ) valproik asit (VPA) kaynaklı pankreas hasarını önleme veya tedavi etmedeki potansiyel etkisinin, sıçanların pankreas dokusundaki gen ekspresyonlarının ve histopatolojik değişikliklerin değerlendirilmesidir. Gereç ve Yöntem: 21 erkek Spraque-Dawley sıçanı 3 gruba ayrıldı (n = 7): Kontrol, VPA, VPA + TQ. Sıçanlar, 14 gün boyunca oral yoldan VPA (500 mg/kg/gün) ve TQ (50 mg/kg/gün) ile muamele edildi. Muamelenin 15. gününde, histon deasetilaz (HDAC1 ve HDAC2) genlerinin ekspresyon seviyelerinin analizi için pankreas dokusu çıkarıldı. Pankreas dokularındaki yapısal değişiklikler incelendi. Bulgular: VPA + TQ grubunun, VPA grubuna göre anlamlı derecede daha yüksek HDAC1 ve HDAC2 gen ekspresyonuna sahip olduğu görüldü. Ayrıca bulgularımız, TQ tedavisinin pankreas dokusunu VPA'nın HDAC1 ve HDAC2 gen ekspresyonu üzerindeki olumsuz etkilerine karşı koruyabildiğini göstermektedir. Ayrıca TQ NADPH oksidaz-4 (NOX-4) ve kaspaz-3 (CAS-3) düzeylerini de düşürdü. VPA+TQ grubunda VPA grubuna göre oksidatif stres azaldı, antioksidan aktivite arttı ve histopatolojik değişiklikler azaldı. VPA'nın neden olduğu pankreas hasarı, TQ'nun antioksidatif ve antiapoptotik etkileri nedeniyle hafifletildi. Sonuç: TQ, VPA'nın neden olduğu pankreas hasarının şiddetini azaltmada faydalı olabilir.

Anahtar Kelimeler:

timokinon, valproik asit, apoptoz, toksisite, HDAC1/2

Effect of thymoquinone on ameliorating valproic acid-induced damage in pancreatic tissue of rats

Purpose: The aim of this study was to evaluate the potential effect of thymoquinone (TQ) in preventing or treating valproic acid (VPA)-induced pancreatic injury, gene expressions and histopathological changes in pancreatic tissue of rats.. Materials and Methods: 21 male Spraque-Dawley rats were divided into 3 groups (n = 7): Control, VPA, VPA + TQ. Rats were treated orally with VPA (500 mg/kg/day) and TQ (50 mg/kg/day) for 14 days. On the 15th day of treatment, pancreatic tissue was resected for the analysis of the expression levels of histone deacetylase (HDAC1 and HDAC2) genes. Structural changes in pancreatic tissues were examined. Results: It was observed that VPA + TQ group had significantly higher HDAC1 and HDAC2 genes expression compared to the VPA group. Furthermore, the findings show that TQ therapy can protect pancreatic tissue against the negative effects of VPA on HDAC1 and HDAC2 gene expression. It also decreased the levels of NADPH oxidase-4 (NOX-4) and caspase-3 (CAS-3). Oxidative stress decreased, antioxidant activity increased and histopathological changes decreased in the VPA + TQ group compared to the VPA group. Pancreatic damage caused by VPA was attenuated due to TQ's antioxidative and antiapoptotic effects. Conclusion: TQ may be useful for reducing the severity of VPA-induced pancreatic damage.

Keywords:

thymoquinone, valproic acid, apoptosis, toxicity, HDAC1/2,

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