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

Yıl 2008, Sayı: 015, 15 - 26, 15.04.2008

M. Dikmen A. Başaran

Öz

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. 

Anahtar Kelimeler

Cisplatin, Rat, Toxicity, Verapamil

CİSPLATİN TOKSİSİTESİ ÜZERİNE KALSİYUM KANAL BLOKÖRLERİNDEN VERAPAMİL'İN ETKİLERİ

Öz

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

Kaynakça

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