M. DİKMEN, A. BAŞARAN

CİSPLATİN TOKSİSİTESİ ÜZERİNE KALSİYUM KANAL BLOKÖRLERİNDEN VERAPAMİL'İN ETKİLERİ

Bu çalışmanın amacı, antineoplastik bir ajan olan cisplatinin toksisitesi üzerine, kalsiyum kanal blokörü olan verapamilin etkilerini araştırmaktır.Bu çalışmada, 42 adet Rattus norvegicus (Wistar albino) soyu, 180-270 g ağırlığında sıçan kullanıldı. Sıçanlar eşit sayıda 6 gruba ayrıldı. Kontrol grubu olan I. gruba 0,3 ml serum fizyolojik, II. gruba 0,2 mg/kg verapamil, III. gruba 2 mg/kg verapamil, IV. gruba 5 mg/kg cisplatin, V. gruba 0,2 mg/kg verapamil ile 5 mg/kg cisplatin ve VI. gruba da 2 mg/kg verapamil ile 5 mg/kg cisplatin verildi. Deneyde, verapamil, cisplatin enjeksiyonundan önce 3 gün boyunca her gün aynı saatte, cisplatin ise verapamil enjeksiyonunun bitiminden sonraki 4. günde tek doz halinde, intraperitoneal olarak uygulandı. Cisplatin enjeksiyonunu takiben 24 saatlik idrar örnekleri toplandı ve deney bitiminde eter anestezisi altında kan, doku ve kemik iliği örnekleri alındı.Çalışma sonunda, kontrole göre sadece cisplatin verilen IV. grupta, serum kreatinin değerinde istatistiksel olarak anlamlı derecede artış bulundu (p<0.001). III., V. ve VI. grupta ise, SGOT aktivitesi (p<0.01) önemli düzeyde azaldı. Kromozomal incelemede de IV., V. ve VI. gruplarda kromatid tipi gap sayısında artış görülse de bu artış kontrole göre anlamlı değildi. Histopatolojik bulgular düşük doz verapamil verdiğimiz V. grupta IV. gruba göre, böbrek dokusunda belirgin bir iyileşme olduğunu gösterdi.Sonuç olarak bu çalışmada, cisplatinin toksisitesi üzerine bazı bulgularda verapamilin koruyucu etki yaptığı, bu koruyucu etkinin düşük doz verapamil verilen V. grupta daha da etkili olduğu tespit edildi.

Anahtar Kelimeler:

Cisplatin, Sıçan, Toksisite, Verapamil

THE EFFECTS OF VERAPAMIL, A CALCIUM CANAL BLOKER, ON CISPLATIN TOXICITY

The aim of this study was investigated to protective effects of calcium chanel blocker verapamil on cisplatin induced toxicity.Fourty-two Rattus norvegicus (Wistar albino) rats were divided into six groups. The control group (I. group) was injected with 0.3 ml saline, II. group was injected with 0.2 mg/kg verapamil, III. group was injected with 2 mg/kg verapamil, IV. group was injected with 5 mg/kg cisplatin, V. group was injected with 0.2 mg/kg verapamil+5 mg/kg cisplatin and VI. group was injected with 2 mg/kg verapamil+5 mg/kg cisplatin. Before cisplatin injection, verapamil was given during the three days at the same hour. After this period, at the fourth day, cisplatin was injected with as a single dose. Following the last dose, within 24 hours urine samples were collected and than blood, kidney and liver tissues samples and bone marrow were collected from the rats under ether anesthesia.At the end of the study, we found that serum creatinine in the IV. group was significantly increased according to control group (p<0.001). SGOT activity was significantly decreased in III., V. and VI. groups (p<0.001). As a result of chromosomal analyses, there were not significantly increased on the number of chromatid typed gaps in the IV., V ve VI. group according to control group. Histopathologic findings showed that a certain recovery was dedected into kidney tissue of the V. group according to kidney tissue of IV.group .As a conclusion, it was determined that verapamil had a protective effect on cisplatin toxicity and this protective effect was high in the V. group which had been given low dose of verapamil.

Keywords:

Cisplatin, Rat, Toxicity, Verapamil,

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