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Siklosporin A Nefrotoksisitesi İçin Rat Modeli: Wistar Soyu Ratlar Üzerinde Bir Çalışma

A Rat Model for Cyclosporine A Nephrotoxicity: A Study on Wistar Strain Rats

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2004

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Nephrotoxicity is a side effect of cyclosporine A (CsA), which is used after transplantation. In CsA-treated patients, factors other than the drug may also have renal and cardiovascular effects. Therefore, experimental models are needed to study adverse effects of only CsA. Since the study was planned to suggest an ideal model for CsA nephrotoxicity, the most appropriate route, duration and dose of administration were determined in male Wistar rats treated with CsA for making functional and morphological nephrotoxicity. CsA were intraperitoneally or subcutaneously administrated to the four groups of rats, in each 2-3, at doses of 20, 30, 40 and 50 mg/kg bw/day, respectively. According to data of this pre-study, study groups were subcutaneously treated with CsA at a dose of 30 mg/kg/day for 30 days, and saline was used for control group. On zero, 10th, 20th and 30th days of the study, plasma BUN and creatinine (Cr) and urine urea nitrogen, Cr and microprotein were analyzed. Urine volumes and weights were recorded. Clearance (CCr) was calculated. Renal tissues were also assessed histologically. There was an increase in plasma BUN and decreases in daily Cr output, CCr, body weights and urine volumes in CsA group by the 10th day of the study. Plasma Cr and urine nitrogen levels were higher on the 30th day, in addition to these toxic effects. In proximal tubules mostly vacuolization, dilatation, necrosis and atrophy were observed in renal histopathology. Our results show that, at a dose of 30 mg/kg/day CsA administrated to male Wistar rats for 30 days resulted in functional and morphologic nephrotoxicity, and also this experimental model may be used in the studies of CsA nephrotoxicity, successfully.
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Abstract (Original Language): 
Transplantasyonda kullanılan siklosporin A (CsA)'nın, başlıca yan etkisi nefrotoksisitedir. CsA tedavisi alan hastalarda, CsA'dan başka faktörler de renal ve kardiyovasküler etkilere yol açabildiğinden; sadece CsA'dan kaynaklanan yan etkilerin ortaya konulmasında, deneysel modellere ihtiyaç duyulmaktadır. Bu çalışma, CsA nefrotoksisitesi için ideal bir deneysel model önerebilmek amacıyla, fonksiyonel ve morfolojik nefrotoksisite oluşturabilen uygun CsA dozunu, uygulama şekli ve süresini belirlemek üzere Wistar erkek ratlar ile yapıldı. Her biri 2-3 rat içeren dört gruba, sırasıyla 20, 30, 40 ve 50 mg/kg/gün dozlarında CsA, ip veya sc olarak uygulandı. Bu ön çalışmanın verilerine göre; CsA'nın sc 30 mg/kg/gün dozunda 30 gün süreyle 10 rata uygulanması planlandı. Kontrol grubuna da ağırlık başına 2.0 ml serum fizyolojik verildi. Çalışmanın 0, 10, 20, 30. günlerinde, ratların plazmasında BUN ve kreatinin (Kr); idrarında üre nitroje¬ni, Kr ve mikroprotein ölçüldü; ratların ağırlıkları ve idrar volümleri belirlendi. Klirens (KKr) hesaplandı. Böbrekler histolojik olarak ince¬lendi. CsA uygulamasının 10. gününden itibaren, plazma BUN'un yükseldiği; günlük Kr atılımının azaldığı; KKr'nin düştüğü; ratların giderek zayıfladığı ve daha az idrar çıkardıkları gözlendi. Otuzuncu günde bu toksisiteye ilaveten, plazma Kr ve idrar üre nitrojeni seviyelerinin de yükseldiği belirlendi. Böbrek patolojisinde, tübüllerde vakuolizasyon başta olmak üzere, dilatasyon, nekroz ve atrofi oluşumu gözlendi. Sonuç olarak, erkek Wistar ratlara sc 30 gün uygulanan 30 mg/kg/gün CsA'nın fonksiyonel ve morfolojik nefrotoksisite oluşturabileceği ve nefrotoksisite çalışmalarında bu modelin başarıyla kulla¬nılabileceği söylenebilir.
FULL TEXT (PDF): 
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  • 3
144-151
  • Turkish

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