MURAT GÖNEN, Tuncay KULOĞLU, MUSTAFA ULAŞ, Ferhat BALGETİR, Caner Feyzi DEMİR, Abdullah BÖYÜK

Sıçan Beyin Dokusunda Takrolimus’un Meydana Getirdiği Değişiklikler Üzerine Vitamin D’nin Etkileri

Amaç: Takrolimus organ nakilleri sonrası yaygın olarak kullanılan kalsinörin inhibitörüdür. Kullanımı sırasında nörolojik komplikasyonlar görülebilmektedir. Bu çalışmada, takrolimus uygulanan sıçanların beyin dokusunda meydana gelen değişiklikler üzerine D vitamininin etkilerinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmada, 21 adet Wistar albino cinsi erkek sıçanlar kullanıldı. Deney hayvanları 3 eşit gruba ayrıldı. Kontrol grubuna deney süresi olan 21 gün boyunca hiçbir uygulama yapılmadı. Takrolimus grubuna takrolimus 0.8 mg/kg/gün, Takrolimus + vitamin D grubuna ise 0.8 mg/kg/gün takrolimus ile birlikte 50 IU/gün dozunda vitamin D deney süresi boyunca oral olarak verildi. Deney sonunda sıçanlar dekapite edildi ve beyin dokuları çıkarıldı. Rutin takip işlemleri ile dokular parafin bloklara gömüldü. Bloklardan alınan kesitlere bax immünreaktivitesi için avidinbiodin-peroksidaz yöntemi, Malondialdehit (MDA) düzeyi için spektrofotometri, apoptozis için TUNEL yöntemi kullanıldı. Bulgular: Kontrol grubuyla karşılaştırıldığında MDA düzeyleri, bax immünreaktivitesi ve TUNEL pozitifliğinde Takrolimus grubunda istatistiksel olarak anlamlı bir şekilde artış saptandı. Takrolimus grubu ile karşılaştırıldığında ise Takrolimus+Vit D grubunda, MDA düzeyleri, bax immünreaktivitesi ve TUNEL pozitifliğinde istatistiksel olarak anlamlı bir azalma izlendi. Sonuç: Bu çalışma takrolimusun beyin dokusunda apoptozisi indüklediğini ve D vitaminin takrolimusun etkilerine karşı koruyucu etkileri olabileceğini göstermiştir.

Effects of Vitamin D on Changes in Rat Brain Tissue Induced by Tacrolimus

Objective: Tacrolimus is a calcineurin inhibitor that is commonly used following transplantation. Neurological complications can be seen during tacrolimus use. In this study it was aimed to investigate effects of vitamin D on changes in brain tissue induced by tacrolimus in rats. Material and Method: The study was conducted on 21 male Wistar Albino rats. Animals were assigned into 3 groups. Control rats received no intervention. Tacrolimus (0.8 mg/kg/day) via oral route was given to rats in tacrolimus group while tacrolimus (0.8 mg/kg/day) plus vitamin D (50 IU/day) via oral route was given to rats in tacrolimus plus vitamin D group for 21 days. At the end of the experiment period, the rats were decapitated and brain tissues were removed. After routine process, tissues were embedded to paraffin blocks. Bax immunoreactivity was assessed with avidinbiotin-peroxidase method while malondialdehyde (MDA) level was assessed by using spectrophotometer in tissue samples. TUNEL method was used to assess apoptosis. Results: When compared to controls, MDA levels, Bax immunoreactivity and TUNEL positivity were significantly increased in tacrolimus group. In addition, there were significant decreases observed in MDA levels, Bax immunoreactivity and TUNEL positivity in tacrolimus plus vitamin D group compared to the tacrolimus group. Conclusion: This study showed that tacrolimus induce apoptosis in brain tissue and vitamin D may have protective effects against the effects of tacrolimus.

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