Saadet ÇELİKÖZLÜ, Filiz ÖZYİĞİT, Said ALTIKAT, Sibel KÖKTÜRK, Halit ÇELİKÖZLÜ

Serebral İskemi/Reperfüzyon Hasarında Hesperidinin Nöroprotektif Etkisi

Amaç: Bu çalışmanın amacı, sıçanlarda serebral iskemi/reperfüzyon hasarına karşı hesperidinin farklı dozlarının koruyucu etkisini araştırmaktır. Gereç ve Yöntemler: Çalışmada kontrol, sham, iskemi/reperfüzyon (İ/R), hesperidin 50 (Hes 50) ve hesperidin 100 (Hes 100) olmak üzere 5 grup hazırlandı. İskemi oluşturmak için Pulsinelli ve Brierly'nin dört damar oklüzyon modeli kullanıldı. 30 dakika iskemi ve 30 dakika reperfüzyon uygulandı. Hesperidin, iskemiden 30 dakika önce intraperitonal olarak enjekte edildi. Histopatolojik çalışma için beyin dokusuna Golgi Cox ve Caspase 3 boyaması uygulandı. Ayrıca beyin dokusunda SOD, CAT, MDA ve total protein seviyeleri belirlendi ve TNF-α mRNA ekspresyon seviyeleri RT-qPCR tekniği ile ölçüldü. Bulgular: İ/R grubunda kontrol grubuna göre CAT ve SOD değerlerinde azalma, MDA değerinde artış, toplam protein değerinde hafif artış saptandı. Hes 50 ve Hes 100 gruplarında, İ/R grubu ile kıyaslandığında CAT, SOD değerleri arttı, MDA ve toplam protein değerleri önemli ölçüde azaldı. I/R grubunda kontrol grubuna kıyasla önemli bir CA1 nöron kaybı gözlendi. Hes 50 grubunda I/R grubuna göre hipokampustaki nöron hasarının azaldığı ve nöron sayısının istatistiksel olarak anlamlı düzeyde arttığı bulundu. Beyin dokusundaki TNF-α mRNA ekspresyon değerleri, I/R grubunda kontrol ve sham gruplarına göre anlamlı derecede yüksekti. Hes 50 grubunda I/R grubuna kıyasla mRNA ekspresyon miktarında önemli bir azalma gözlendi. Sonuç: Bu çalışmanın sonuçlarına göre, antioksidan potansiyeli olan hesperidin, serebral iskemi/reperfüzyonunun neden olduğu oksidatif stres hasarına karşı nöroprotektif ve antiinflamatuar etkiler göstermiştir. Düşük doz hesperidin (Hes 50) grubunda antiinflamatuar ve nöroprotektif etkiler öne çıkarken, hem Hes 50 hem de Hes 100 gruplarında antioksidan etkinin daha baskın olduğu tespit edilmiştir.

Anahtar Kelimeler:

Serebral iskemi, Reperfüzyon, Hesperidin, Koruyucu etki

Neuroprotective Effects of Hesperidin In Cerebral Ischemia/Reperfusion Injury

Aim: The aim of this study was to investigate the protective effect of different doses of hesperidin against cerebral ischemia/reperfusion injury. Material and Method: In this study, 5 groups were prepared as control, sham, ischemia/reperfusion (I/R), hesperidin50 (Hes 50), and hesperidin100 (Hes 100). Four vessel occlusion model was used to induce ischemia. 30minutes of ischemia and 30minutes of reperfusion were applied. Hesperidin was injected intraperitoneally 30minutes before ischemia. GolgiCox and Caspase3 staining were performed, SOD, CAT, MDA, and total protein levels were determined, TNF-α mRNA expression levels were measured in brain tissue. Results: In the I/R group, CAT and SOD values decreased, the MDA value increased, a slight increase in the total protein value was found compared to the control group. CAT, SOD values increased, MDA and total protein values decreased significantly in Hes 50 and Hes 100 groups. A significant loss of CA1 neurons was observed in the I/R group. It was found that neuron damage in the hippocampus decreased and the number of neurons increased statistically significantly in the Hes 50 group compared to the I/R group. TNF-α mRNA expression values in brain tissue were significantly higher in the I/R group than control and sham groups. A significant decrease in the amount of mRNA expression was observed in the Hes50 group compared to the I/R group. Conclusion: According to the results of this study, hesperidin, which has antioxidant potential, showed neuroprotective and anti-inflammatory effects against oxidative stress damage caused by cerebral ischemia/reperfusion. While anti-inflammatory and neuroprotective effects were prominent in the low-dose hesperidin (Hes 50) group, the antioxidant effect was more dominant in both Hes 50 and Hes 100 groups.

Keywords:

Cerebral ischemia, Reperfusion, Hesperidin, Protective effect,

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