ÖZGÜR VATAN, Deniz BAĞDAŞ, Nilüfer ÇİNKILIÇ, Axel WEHREND, Gözde Rabia ÖZALP

Genotoxic and cytotoxic effects of the aglepristone, A progesteron antagonist, in Mid-gestation pregnancy termination in rabbits

Aglepriston, veteriner hekimlikte gebeliklerin sonlandırılmasında kullanılan bir antiprogestindir. Aglepristonun yan etkileri ile ilgili bilgiler sınırlıdır. Çalışmamızın amacı; orta gebelikte gebeliği sonlandırılan tavşanlarda aglepristonun potansiyel sitotoksik ve genotoksik etkilerinin araştırılmasıdır. Çalışmada 15 Yeni Zelanda beyaz tavşanı kullanılmıştır ve gebe tavşanlar rastgele üç gruba ayrıldı. I. Grup (n=5) kontrol grubu olarak tuz çözeltisi ile muamele edildi. II. Grup (n=5) gebeliğin 15. gününde aglepriston (10 mg/kg) enjekte edilen III. Grup (n=5) ise gebeliğin 15. ve 16. günlerinde aglepristone enjekte edilen gruptu. Tavşanlar son enjeksiyonlardan 24 saat sonra giyotin ile sakrifiye edilerek hızlı bir şekilde kemik iliği ve kan örnekleri alındı. Sitotoksik ve genotoksik potansiyel mikroçekirdek ve komet yöntemleri ile araştırıldı. Tek aglepriston uygulaması ile gebeliği sonlandırılan tavşanlarda mikroçekirdek testi ile herhangi bir sitotoksik ve genotoksik etki belirlenemedi. Bunun tersine iki aglepriston uygulanan tavşanların kemik iliği hücrelerinde yüksek sitotoksik ve genotoksik etki belirlendi. Komet yönteminde kullanılan kan örneklerinde gruplar arasında bir fark belirlenemedi. Kemik iliği hücrelerinin kullanıldığı komet yönteminde tek enjeksiyon grubunda herhangi bir DNA hasarı belirlenmemesine rağmen çift enjeksiyon grubunda DNA hasarının arttığı belirlendi.

Tavşanlarda orta dönem gebelikleri sonlandırılmasında kullanılan bir progesteron antagonisti olan aglepristonun genotoksik ve sitotoksik etkileri

Aglepristone is an antiprogestin using for pregnancy termination in veterinary medicine. The information about side effects of aglepristone is limited. The aim of the study was to investigate cytotoxicity and genotoxicity of aglepristone in mid-gestation pregnancy termination in rabbits. Fifteen New Zealand White rabbits were used and pregnant does were randomly divided into three groups. Group I (n=5) was treated with saline as the control. The does in group II (n=5) and group III (n=5) were treated with aglepristone (10 mg/kg) on 15 th day and 15 th-16 th days of pregnancy, respectively. The rabbits were sacrificed by guillotine 24 h after last treatment. Bone marrow and blood samples were immediately collected. Cytotoxic and genotoxic potential were tested by micronucleus and Comet assays. No genotoxicity and cytotoxicity were found in micronucleus test with single aglepristone administration. In contrast, two consecutive treatments of aglepristone showed high genotoxic and cytotoxic efects on bone marrow in animals. While comet assay of blood samples did not show any significant diference between groups; the results from comet assay of bone marrow cells showed the single injection of aglepristone did not induce any DNA damage but two injections group increased the DNA damage.

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