Mehmet Ural, Meltem Özgüner, Dilek Şenal, Recep Sütçü, Namık Delibaş

Siklosporin A'nın sıçanlarda oluşturduğu nefrotoksisiteye Vitamin C ile Vitamin E'nin ve verapamilin etkilerinin ışık mikroskobunda değerlendirilmesi

SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2005 Aralık; 12(4) Siklosporin A'nın sıçanlarda oluşturduğu nefrotoksisiteye Vitamin C ile Vitamin E'nin ve verapamilin etkilerinin ışık mikroskobunda değerlendirilmesi Mehmet Ural, Meltem Özgüner, Dilek Şenal, Recep Sütçü, Namık Delibaş Özet Amaç: Siklosporin A (CsA) organ nakillerinde atılımı önlemede önemli bir kullanım alanına sahiptir. Bu güçlü bağışıklık sistemini baskılayıcı ajanın en önemli yan etkisi nefrotoksisitedir. Bu yan etkinin oluşumunda suçlanan en önemli iki mekanizma; i) böbrekte afferent arteriyolde yaptığı vazokonstrüksiyon ii) antioksidan sistem enzimleri üzerine yaptığı etki serbest oksijen radikallerini arttırmasıdır. CsA uygulanan deneklere antioksidan özelliği olan Vit E ve Vitamin C ile birlikte kalsiyum kanallarını bloke ederek vazodilatatör etkinlik gösteren verapamili vererek, farklı deney gruplarında böbrek korteksindeki histopatalojik değişiklikleri değerlendirmek ve bu değişikliklere antioksidan ve vazodilatatör ajanların tek tek ve birlikte verildiklerindeki etkilerini araştırmak amacıyla bu çalışmayı yaptık. Materyal ve Metod: 25 sıçan; kontrol grubu, siklosporin A (CsA) verilen grup, CsA+ vitamin E ve C verilen grup, CsA+verapamil verilen grup ve CsA+vitamin+verapamil verilen grup olmak üzere beş gruba ayrıldı. 10 gün boyunca CsA nazogastrik sonda ile oral olarak 50 mg/kg dozunda, E vitamini 150 mg/kg dozunda intramüsküler olarak; C vitamini 200 mg/kg dozunda intraperitoneal olarak, verapamil 0.5 mg/kg dozunda intramüsküler olarak verildi. Çalışmanın sonunda sıçanların kanları ve böbrek dokuları eter anestezisi altında alındı. Böbrek dokusu %10'luk formolde tespit edildi. Rutin histolojik takip ile bloklanan dokulardan 5ïm 'lik kesitler alındı ve hematoksilen-eozin ile boyanarak değerlendirildi. Bulgular: Çalışmamızın sonunda CsA verilen grupta histolojik olarak belirgin yapısal değişiklikler ortaya çıktı. Bu değişiklikler CsA + vitamin E ve C verilen grup ve CsA + verapamil verilen gruplarda kısmen düzelmekle birlikte; normal histolojik yapıya en yakın görünüm CsA + vitamin + verapamil alan grupta görüldü. Ayrıca böbrek dokusunda antioksidan enzimlerden glutatyon proksidaz ve katalazda en belirgin yükselme ve böbrek fonksiyon testlerinden BUN ve kreatinin de en belirgin düzelme de bu grupta izlendi. Sonuç: CsA'nın yaptığı nefrotoksisitenin önlenmesi için; verapamil, vitamin E ve C'nin birlikte kullanılmasının daha faydalı olacağı kanaatindeyiz. Anahtar kelimeler: Siklosporin A, Nefrotoksisite, Verapamil, Vitamin E, Vitamin C Abstract Effects of Vitamin C, Vitamin E and verapamil on cyclosporin induced nephrotoxicity in rats: a light microscobic study Aim: Cyclosporin A (CsA) is an important agent used in organ transplantation to prevent rejection. This immunosupressive drug's most important secondary effect is nephrotoxicity. There are two hypotheses for the nephrotoxicity mechanism i) vasoconstruction in afferent arteriole ii) the role of reactive oxygen species. In this study we planned to see the individual or combined effects of antioxidant vitamins E and C with a calcium channel blocker verapamil. Materials and Methods: 25 rats divided into five groups equally; a vehicle group, CsA treated group, CsA + vitamin E and C treated group, CsA + verapamil treated group and CsA+ vitamin E and C + verapamil treated group. CsA administered 50 mg/kg/day (per oral by catheter), vitamin E administered 150 mg/kg/day (intramusculer), vitamin C administered 200 mg/kg/day (intraperitoneal), verapamil administered 0.5 mg/kg/day (intramusculer) for 10 days. At the end of study rats' blood samples and kidney tissues were taken under ether anesthesia. Tissue sections of kidney were fixed in %10 formalin. Parafin sections were cut at 5 ïm, then examined after staining with hematoxylin-eosin. Results: In CsA treated rats, significant morphological changes were observed in kidney sections. Although in CsA + vitamin E,C and CsA + verapamil treated rats, these changes were reduced but the most significant improvement observed in the CsA + vitamin C and E + verapamil treated group. Also most significant rise of antioxidant enzymes, catalaz and glutathion peroxidase in renal tissue was seen in this group. Conclusion: We suggest that using the combination of verapamil, vitamin E and C will be more useful to prevent the nephrotoxicity caused by CsA. Key words: Cyclosporin A, Nephrotoxicity, Verapamil, Vitamin E, Vitamin C

Anahtar Kelimeler:

Siklosporin A, Nefrotoksisite, Verapamil, Vitamin E, Vitamin C

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