Gonadotoxic Effects of Nilotinib in Chronic Myeloid Leukemia Treatment Dose in a Mouse Model [Turk J Hematol]
Turk J Hematol. 2017; 34(2): 137-142 | DOI: 10.4274/tjh.2016.0092  

Gonadotoxic Effects of Nilotinib in Chronic Myeloid Leukemia Treatment Dose in a Mouse Model

Güldane Seval1, Sinan Özkavukçu2, Murat Seval3, Meltem Aylı1
1Ufuk University Faculty of Medicine, Department of Hematology, Ankara, Turkey
2Ankara University Faculty of Medicine, Department of Obstetrics and Gynecology, Center of Assisted Reproduction, Ankara, Turkey
3Ankara University Faculty of Medicine, Department of Obstetrics and Gynecology, Ankara, Turkey

Objective: Tyrosine kinase inhibitors may have deleterious effects on spermatogenesis or folliculogenesis, resulting in male or female subfertility. The aim of this study is to determine the effect of nilotinib, which is used routinely to treat chronic myeloid leukemia, on spermatogenesis and folliculogenesis by using histopathological parameters.
Materials and Methods: Ten male and ten female mice were orally treated with nilotinib at 20 mg/kg body weight dissolved in drinking water daily for 2 months
Results: When compared with the control group, a statistically significant decrease was demonstrated in the total follicle numbers of the female mice in the nilotinib group (268±110 vs. 170±60; p=0.03). Active spermatogenesis was observed in each tubule sample taken from the mice in the control and nilotinib groups. Spermatogenic activity was similar in the two groups.
Conclusion: We have demonstrated that even though spermatogenesis is preserved, folliculogenesis is inhibited by the usage of a continuous nilotinib treatment dose in chronic myeloid leukemia.

Keywords: Chronic myeloid leukemia, Nilotinib, Fertility, Mouse, Gonads


Kronik Miyeloid Lösemi Tedavi Dozunda Nilotinib’in Gonadotoksik Etkilerinin Fare Modelinde Gösterilmesi

Güldane Seval1, Sinan Özkavukçu2, Murat Seval3, Meltem Aylı1
1Ufuk University Faculty of Medicine, Department of Hematology, Ankara, Turkey
2Ankara University Faculty of Medicine, Department of Obstetrics and Gynecology, Center of Assisted Reproduction, Ankara, Turkey
3Ankara University Faculty of Medicine, Department of Obstetrics and Gynecology, Ankara, Turkey

Amaç: Tirozin kinaz inhibitörlerinin; potansiyel gonadotoksisite ve döllenme üzerindeki olası etkileri hakkında kesin veriler bulunmamaktadır. Bu çalışmanın amacı sağlıklı fare modelinde nilotinib tedavisinin fertilite üzerine etkilerini araştırmaktır
Gereç ve Yöntem: On erkek ve on dişi fareye 20 mg/kg/gün nilotinib içme suyuna katılarak 2 ay süre ile verildi.
Bulgular: Folikül sayılarında nilotinib verilen dişi fare grubunda kontrol grubuna göre istatistiksel olarak anlamlı bir azalma olduğu gözlendi (268±110 vs. 170±60; p=0,03). Kontrol ve nilotinib gruplarındaki farelerden alınan her seminifer tübül örneğinde spermatid veya spermatozoa olan aktif spermatogenez gözlendi. Spermatojenik aktivite indeksi her iki grupta da benzerdi.
Sonuç: Bizim çalışmamız ile kronik miyeloid lösemide tedavi dozunda ve uzun süreli nilotinib kullanımı ile spermatogenez korunurken folikülogenezin baskılandığı gösterilmiştir.

Anahtar Kelimeler: Kronik miyeloid lösemi, Nilotinib, Doğurganlık, Fare, Gonad


Güldane Seval, Sinan Özkavukçu, Murat Seval, Meltem Aylı. Gonadotoxic Effects of Nilotinib in Chronic Myeloid Leukemia Treatment Dose in a Mouse Model. Turk J Hematol. 2017; 34(2): 137-142

Corresponding Author: Güldane Seval, Türkiye


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