Betül CAN, Semih ÖZ, Ahmet MUSMUL, Tuğba ERKMEN, Ezgi YAVER, Meltem ERDAŞ, Özkan ALATAŞ

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Bilateral Karotis Arter Oklüzyonu Sonrasında Conivaptan ve Mannitol’ün Serum Sitokin (TNF-α, IL-15 ve IL-35) Düzeyleri Üzerine Etkileri

Bu çalışmada, deneysel serebral iskemi-reperfüzyon hayvan modelinde akuaretik Conivaptan ve diüretik Mannitol tedavilerinin serum tümör nekroz faktör-α (TNF-α), interlökin-15 (IL-15) ve interlökin-35 (IL-35) düzeylerine post-iskemik etkilerinin araştırılması amaçlanmıştır. Sağlıklı erkek Sprague-Dawley sıçanlar rastgele 5 gruba ayrılmıştır: Kontrol (Sham), I/R (I/R+Salin), MAN (I/R+Mannitol), CON10 (I/R+Conivaptan 10 mg/ml), and CON20 (I/R+Conivaptan 20 mg/ml). Serebral iskemi, bilateral kommon karotis arter oklüzyonu tekniği kullanılarak gerçekleştirilmiştir. Reperfüzyonun başlangıcında salin, conivaptan veya mannitol intravenöz yolla uygulanmıştır. Kan örnekleri reperfüzyonun 6. saatinde alınmıştır. Sıçan TNF-α, IL-15 ve IL-35 serum düzeyleri ticari ELISA kitleri kullanılarak ölçülmüştür. Biyokimyasal analizler, I/R uygulamasının TNF-α ve IL-15 düzeylerinde kontrole göre artışa yol açtığını göstermiştir. Conivaptan tedavileri TNF-α ve IL-15 düzeylerini I/R grubuna göre anlamlı düzeyde azaltmıştır (p<0.001). IL-35 düzeyleri tüm iskemi gruplarında yüksek bulunurken, 10 mg/ml Conivaptan tedavisi IL-35 düzeylerini kontrol grubu düzeylerine yaklaştırmıştır (p<0.001). Yapılan Spearman korelasyon analizleri, serum TNF-α düzeylerinin IL-15 (p<0.001, r=0.596) ve IL-35 (p<0.05, r=0.319) düzeyleri ile pozitif yönde ilişkili olduğunu göstermiştir. Sonuç olarak pro-inflamatuar ve anti-inflamatuar bu sitokin düzeylerine dair bulgularımız, Conivaptan’ın doza bağlı olarak inflamatuar yanıtın dengelenmesinde Mannitol’den daha etkili olduğunu göstermektedir. Bu çalışma, inme ve beyin ödemi gibi iskemi ve inflamasyon ile ilişkili hastalıkların tedavi ve takibine yönelik stratejilerin geliştirilmesinde yararlı bilgiler sağlayabilir.
Anahtar Kelimeler:

beyin ödemi, conivaptan, interlökin, mannitol, serum sitokinleri

Effects of conivaptan and mannitol on serum cytokine levels (TNF-α, IL-15 and IL-35) following bilateral carotid artery occlusion

This study was aimed to investigate the post-ischemic effects of aquaretic conivaptan and diuretic mannitol on serum tumor necrosis factor-α (TNF-α), interleukin-15 (IL-15) and interleukin-35 (IL-35) levels in an experimental cerebral ischemia-reperfusion (I/R) rat model. Healty male Sprague-Dawley rats were randomly divided into five groups: Control (Sham), I/R (I/R+Saline), MAN (I/R+mannitol), CON10 (I/R+conivaptan 10 mg/ml), and CON20 (I/R+conivaptan 20 mg/ml). Cerebral ischemia was conducted using bilateral common carotid artery occlusion technique. At the onset of reperfusion, saline, conivaptan or mannitol were administrated intravenously. The blood samples were taken at 6th hours of reperfusion. Rat serum TNF-α, IL-15 and IL-35 levels were measured by using commercial ELISA Kits. The biochemical analyses showed that I/R method led to an increase in serum TNF-α and IL-15 levels when compared with the control. Conivaptan treatments decreased TNF-α and IL-15 levels significantly compared to the I/R group (p<0.001). IL-35 levels were high in all ischemia groups, but 10 mg/ml conivaptan brought its levels close to the control (p<0.001). The results of Spearman’s correlation analyses showed that serum TNF-α levels were positively correlated with IL-15 levels (p<0.001, r=0.596) and IL-35 levels (p<0.05, r=0.319). According to our findings on pro-inflammatory and anti-inflammatory cytokine levels, conivaptan was dose-dependently more effective than mannitol in balancing inflammatory response. This study may provide useful information in the development of treatment/follow-up strategies for ischemia and inflammation related diseases such as stroke and brain edema.
Keywords:

brain edema, conivaptan, interleukin, mannitol, serum cytokines,

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Eurasian Journal of Biological and Chemical Sciences-Cover
  • Yayın Aralığı: Yılda 2 Sayı
  • Başlangıç: 2018
  • Yayıncı: Muhammet DOĞAN
Arşiv
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