Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Sisplatin Nefrotoksisitesi Oluşturulan Sıçanların Plazma Glutatyon Peroksidaz, Süperoksit Dismutaz, Adenozin Deaminaz Aktiviteleri ve Nitrik Oksit Seviyelerine Ginkgo Biloba Ekstraktının Etkileri
THE EFFECTS OF GINKGO BILOBA EXTRACT ON PLASMA GLUTATHION PEROXIDASE, SUPEROXIDE DISMUTASE, ADENOSINE DEAMINASE AND NITRIC OXIDE LEVELS IN CISPLATIN-INDUCED NEPHROTOXICITY
Mukaddes GÜLEÇa, H. Ramazan YILMAZb, Mustafa IRAZc, Seda AĞLAMIŞc, Sadık SÖĞÜTd
aBiyokimya, cFarmakoloji AD, İnönü Üniversitesi Tıp Fakültesi, MALATYAbTıbbi Biyoloji ve Genetik AD, Süleyman Demirel Üniversitesi Tıp Fakültesi, ISPARTAdBiyokimya AD, Mustafa Kemal Üniversitesi Tıp Fakültesi, HATAY
Turkiye Klinikleri J Med Sci. 2004;24(6):585-91
Article Language: TR
Full Text
ÖZET
Amaç: Sisplatin (CDDP) geniş spekturumlu platin türevi bir antineoplastik ajandır. Kuvvetli nefrotoksisite riskinden dolayı tedavide kullanımı oldukça kısıtlıdır. CDDP'nin böbrek dokusunda yaptığı hasarın altında yatan mekanizma büyük oranda reaktif oksijen ürünleri (ROS)'ne bağlıdır. Ginkgo biloba ekstraktı (GBE)= Egb 761, birçok organ ve dokunun birbirinden farklı ama ortak olarak serbest radikallerin öncelikli rol oynadığı patolojilerinde kullanılmakta olup tedavide faydalı etkisi olduğu görülmüştür. Bu çalışma GBE'nin sisplatin nefrotoksisitesine karşı koruyucu etkisinin olup olmadığını tespit etmek amacıyla planlanmıştır. Gereç ve Yöntemler: Bu çalışmada erkek Sprague Dawley sıçanlar (60 günlük) kullanıldı. Hayvanlar rastgele seçilerek 4 gruba ayrıldı: Kontrol grubu (n= 7), IP 7 mg/kg'dan tek doz CDDP (Cisplatin, Ebewe) uygulanan grup (n= 8), CDDP ile birlikte IP 10 mg/kg E-vit (Evigen-Aksu) verilen grup (n= 9), CDDP ile birlikte oral 100 mg/kg GBE uygulanan grup (n= 7). Deneysel işlemlerden 10 gün sonra hayvanların kanları alınarak uygulanan ajanların plazma oksidan/antioksidan sisteme olan etkileri araştırıldı. Bulgular: Veriler istatistiksel olarak incelendiğinde; CDDP alan sıçanların plazma glutatyon peroksidaz (GSH-Px) aktivitesinde azalma söz konusu iken, adenozin deaminaz (ADA) aktivitesinde ve nitrik oksit (NO) değerlerinde artışa rastlanmıştır. Plazma süperoksit dismutaz (SOD) aktivitesinde, gruplar arasında herhangi bir değişiklik olmamıştır. CDDP + E-vit verilmesi ile GSH-Px ve ADA aktivitelerinde kontrole yakın olmak üzere NO değerlerinde de bir düzelme gözlenmiştir. CDDP + GBE alan grubun GSH-Px aktiviteleri sadece CDDP alan gruba göre anlamlı derecede artmıştır (p< 0.014). GBE aynı zamanda CDDP ile artmış olan ADA ve NO değerlerinde istatistiksel olarak anlamlı olmayan belirgin bir azalma sağlamıştır. Sonuç: Bu sonuçlara göre CDDP ile oluşturulan nefrotoksisitenin temelinde hücre savunma sisteminin bozulması söz kosudur. Antioksidan özelliği olan GBE, burada kısmen koruyucu bir etkinlik göstermiştir. CDDP nefrotoksisitesinde GBE'nin kesin tedavi edici bir ilaç olarak değerlendirilebilmesi için henüz çok erkendir. Bu nedenle farklı doz, farklı süre ve farklı denek sayılarıyla yeni çalışmaların yapılması uygun olacaktır.

Anahtar Kelimeler: Sisplatin nefrotoksisitesi, ginkgo biloba, glutatyon peroksidaz, süperoksit dismutaz, adenozin deaminaz, nitrik oksit
ABSTRACT
Objective: Cisplatin (CDDP), derived from platinium, is a broad-spectrum antineoplastic agent. It has not commonly been used as a therapeutic agent because of its nephrotoxicity risk. The underlying mechanism in nephrotoxi-city has been attributed to reactive oxygen species (ROS). Gingko biloba extract (GBE, Egb 761) has been shown to be effective on some organ and tissue pathologies induced by ROS. The aim of this experimental study was to determine whether antioxidant GBE has a preventive effect on nephrotoxi-city induced by CDDP through oxidative damage. Material and Methods: Male Sprague Dawley rats (60 days old) were used in the experiments. Rats were randomly assigned to one of four groups: control or untreated rats (n=7); rats treated with i.p. injection in a single dose of 7 mg/kg body wt CDDP (Cisplatin, Ebewe) (n=8); rats treated with CDDP plus i.p. injection of 10 mg/kg body wt vitamin E (Evigen-Aksu, Turkey) (n=9); and rats treated with CDDP plus oral administration of GBE in a dosage of 100 mg/kg body wt (n=7). After 10 days of experimental procedure, animals were euthanized by bleeding, kidneys were removed and oxidant and antioxidant parameters were examined to determine the effects of agents as applied to the rats. Results: In treated rats, the activity of plasma glutathion peroxidase (GSH-Px) was decreased, but adenosine deaminase (ADA) and nitric oxide (NO) levels were increased with CDDP. The activity of superoxide dismutase (SOD) remained unchanged in all study groups. Upon treating the rats with CDDP + vit E, the activities of GSH-Px and ADA, and the level of NO were improved. In the case of CDDP + GBE application, we determined an increased activity of GSH-Px in comparison with the rats treated with CDDP (p<0.014). GBE also decreased the levels of ADA and NO, which were increased in the CDDP-treated group. Conclusion: In keeping with the results, the main underlying mechanism in CDDP-induced nephrotoxicity appears to be due to renal tubular cell damage. GBE appeared to induce a beneficial therapeutic effect in this study. However, we can not yet consider GBE to be a new therapeutic agent in CDDP nephrotoxicity until further studies with various doses, different time intervals, and more animal numbers have been provided.

Keywords: Cisplatin nephrotoxicity, ginkgo biloba, glutathione peroxidase, superoxide dismutase, adenosine deaminase, nitric oxide

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