Sıçan ovaryum dokusunda doksorubisin ile indüklenmiş folliküler apoptotik aktivasyonda Dialil Disülfit’in koruyucu etkisi
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Date
2019-06-24
Authors
Şen, Esra
Journal Title
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Publisher
Uludağ Üniversitesi
Abstract
Doksorubisin; sarkomların, meme ve akciğer kanserleri de dahil olmak üzere karsinomların, akut lenfositik lösemilerin ve lenfomaların tedavisinde önemli ve en sık kullanılan kemoterapötik ilaçlardan birisidir. Doksorubisinin de aralarında olduğu antrasiklin türevi antibiyotikler iki DNA zinciri arasına yerleşerek DNA ve RNA sentezini inhibe ederler ve topoizomeraz II enzimi üzerinden de DNA zincir kırılmalarına sebep olurlar. Bu çalışmada doksorubisinin ovaryum üzerindeki toksisitesini belirlemek ve ovaryan toksisite üzerine dialil disülfitin etkinliğini değerlendirmek amaçlandı. Çalışma kapsamında 35 adet 2,5-3 aylık Wistar albino cinsi dişi sıçan 5 gruba ayrıldı: Grup I: Kontrol-Doksorubisin Grubu, Grup II: Kontrol-Dialil disülfit Grubu, Grup III: Doksorubisin Uygulanan Grup, Grup IV: Dialil disülfit Uygulanan Grup, Grup V: Doksorubisin + Dialil disülfit Uygulanan Grup. Doksorubisin 3 mg/kg/gün (0,008 mM/7 gün, 10 mg/kg- 5 ml enjeksiyonluk su) intraperitoneal (ip) olarak enjekte edildi. Dialil disülfit 0,5 ml mısır yağı içerisinde 50 mg/kg ip enjeksiyon şeklinde uygulandı. Morfolojik değişiklikler hematoksilen eozin boyamasında ışık mikroskobik değerlendirme ve follikül sayımı ile gerçekleştirildi. Apoptotik aktivasyon TUNEL yöntemi ile değerlendirildi. Çalışmanın sonucunda elde ettiğimiz bulgulara göre, doksorubisinin vücut ağırlığını azalttığı gözlendi. Follikül sayımı sonrasında gruplar arasında unilaminar primer ve multilaminar primer folliküller düzeyinde istatistiksel olarak anlamlılık görülmezken, doksorubisin grubunda primordiyal follikül sayılarında istatistiksel olarak anlamlı düzeyde azalma belirlendi. Doksorubisin grubunda kontrol-doksorubisin, kontrol-dialil disülfit, dialil disülfit ve doksorubisin+disülfit gruplarına göre sekonder ve graaf follikül sayılarında azalmalar olduğu, atretik follikül sayılarında ise anlamlı derecede artış olduğu görüldü. Doksorubisin+dialil disülfit grubunda sekonder ve graaf follikül sayılarının kontrol (doksorubisin ve dialil disülfit) ve dialil disülfit grubu ile benzer olduğu, atretik follikül sayılarının doksorubisin grubuna kıyasla anlamlı derecede azaldığı saptandı. Doksorubisin ile birlikte verilen dialil disülfitin ovaryan follikül rezervini koruduğu ve ovaryan toksisiteyi azaltabileceği sonucuna varıldı.
Doxorubicin is one of the most important and most frequently used chemotherapeutic drugs for the treatment of carcinomas, acute lymphocytic leukemias and lymphomas including sarcomas, breast and lung cancers. Anthracycline-derived antibiotics are located between two DNA strands, inhibiting DNA and RNA synthesis, and causing DNA chain breaks through topoisomerase II. The aim of this study was to determine the toxicity of doxorubicin, an anthracycline-derived antibiotic, on the ovary and to evaluate the effectiveness of diallyl disulfide on ovarian toxicity. In this study, 2.5-3 month old 35 female Wistar albino rats were divided into 5 groups: Group I: Control-Doxorubicin Group, Group II: Control-Dialyl disulfide Group, Group III: Doxorubicin Applied Group, Group IV: Dialil disulfide Applied Group , Group V: Doxorubicin + Dialil disulfide Group. Doxorubicin 3 mg / kg / day (0.008 mM / 7 days) doxorubicin (10 mg / kg-5 ml water for injection) was injected intraperitoneally (ip). Dialil disulfide was administered as 50 mg / kg ip injection in 0.5 ml corn oil. Morphological changes were performed by light microscopic evaluation and follicle counting in hematoxylin eosin staining. Apoptotic activation was evaluated by TUNEL method. According to the results of the study, doxorubicin was found to decrease the body weight. There was no statistically significant difference between the unilaminar primary and multilaminar primary follicles in the follicle group after the follicle count, but a statistically significant decrease in the number of primordial follicles in the doxorubicin group. In the doxorubicin group, there were decreases in the number of secondary and graaf follicles according to the control-dokrorubicin, control-diallyl disulfide, diallyl disulfide and doxorubicin + disulfide groups, and there was a significant increase in the number of atretic follicles. In the Doxorubicin + diallyl disulfide group, the number of secondary and graaf follicles was similar to the control (doxorubicin and diallyl disulfide) and diallyl disulfide group, and the number of atretic follicles decreased significantly compared to the doxorubicin group. It was concluded that dialil disulphide provided with doxorubicin could reduce this damage in the ovary and protect the ovarian follicle reserve.
Doxorubicin is one of the most important and most frequently used chemotherapeutic drugs for the treatment of carcinomas, acute lymphocytic leukemias and lymphomas including sarcomas, breast and lung cancers. Anthracycline-derived antibiotics are located between two DNA strands, inhibiting DNA and RNA synthesis, and causing DNA chain breaks through topoisomerase II. The aim of this study was to determine the toxicity of doxorubicin, an anthracycline-derived antibiotic, on the ovary and to evaluate the effectiveness of diallyl disulfide on ovarian toxicity. In this study, 2.5-3 month old 35 female Wistar albino rats were divided into 5 groups: Group I: Control-Doxorubicin Group, Group II: Control-Dialyl disulfide Group, Group III: Doxorubicin Applied Group, Group IV: Dialil disulfide Applied Group , Group V: Doxorubicin + Dialil disulfide Group. Doxorubicin 3 mg / kg / day (0.008 mM / 7 days) doxorubicin (10 mg / kg-5 ml water for injection) was injected intraperitoneally (ip). Dialil disulfide was administered as 50 mg / kg ip injection in 0.5 ml corn oil. Morphological changes were performed by light microscopic evaluation and follicle counting in hematoxylin eosin staining. Apoptotic activation was evaluated by TUNEL method. According to the results of the study, doxorubicin was found to decrease the body weight. There was no statistically significant difference between the unilaminar primary and multilaminar primary follicles in the follicle group after the follicle count, but a statistically significant decrease in the number of primordial follicles in the doxorubicin group. In the doxorubicin group, there were decreases in the number of secondary and graaf follicles according to the control-dokrorubicin, control-diallyl disulfide, diallyl disulfide and doxorubicin + disulfide groups, and there was a significant increase in the number of atretic follicles. In the Doxorubicin + diallyl disulfide group, the number of secondary and graaf follicles was similar to the control (doxorubicin and diallyl disulfide) and diallyl disulfide group, and the number of atretic follicles decreased significantly compared to the doxorubicin group. It was concluded that dialil disulphide provided with doxorubicin could reduce this damage in the ovary and protect the ovarian follicle reserve.
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Keywords
Doksorubisin, Doxorubicin, Dialil disülfit, Apoptoz, Dialil disulfide, Apoptosis
Citation
Şen, E. (2018). Sıçan ovaryum dokusunda doksorubisin ile indüklenmiş folliküler apoptotik aktivasyonda Dialil Disülfit’in koruyucu etkisi. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.