Bleomisin etoposid cis-platin tedavisi uygulanan sıçan modellemesinde oluşan sperm DNA fragmantasyonuna glutatyonun etkisi
Yükleniyor...
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
T.C. Maltepe Üniversitesi Lisansüstü Eğitim Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Testis kanseri üreme çağındaki genç erkeklerde (20-40 yaş) sık görülen malign tümörlerdendir. Tedavisinde kullanılan cis-platin bazlı kemoterapötik ajanlar ve spesifik Bleomisin, Etoposit ve cis-platin (BEP) kombinasyonu sağ kalımı arttırırken sağlıklı dokularda da hasar oluşmasına neden olmaktadır. Hasar oluşturduğu önemli dokulardan biri de testis dokusu ve sperm hücreleridir. Bu çalışmada uygulanan BEP tedavisinin sıçanlarda oluşturduğu sperm DNA bütünlüğü ve testis histomorfolojisi hasarları üzerine glutatyon (GSH) uygulamasının koruyucu etkisi araştırıldı. Üreme çağındaki 12 haftalık erkek sıçanlar (n=24) rastgele her grupta 8 tane olacak şekilde kontrol, BEP ve BEP+GSH olarak 3 gruba ayrıldı. BEP grubuna 9 hafta boyunca her biri 21 günlük 3 kür olacak şekilde ön çalışmada belirlenen BEP dozlarına göre (0,083; 0,83; 0,17 mg/kg) tedavi intraperitonal olarak uygulandı. BEP+GSH grubuna BEP grubuna uygulanan kemoterapötik tedaviyle birlikte 9 hafta boyunca, her hafta düzenli olarak, haftanın 1.ve 4.gunlerinde Glutatyon 200 mg/kg uygulandı. Kontrol grubuna ise diğer gruplara ilaç uygulanan günlerde %0,9 NaCl intraperitonal olarak verildi. Grupların ağırlık artışları karşılaştırıldığında BEP+GSH grubunun ağırlık artışı BEP grubunun ağırlık artışına göre anlamlılık göstermedi (p=0,921). Kontrol grubundaki artış BEP grubu ve BEP+GSH grubuna göre yüksek bulundu (p?0,027, p?0,012). Benzer şekilde kontrol grubunun sol testis ağırlıkları (p?0,017; p?0,003), sol epididimis ağırlıkları (p?0,029; p?0,037), sağ epididimis ağırlıkları (p?0,002; p?0,004), testis ağırlık indeksleri (p?0,0017; p?0,001) BEP grubu ve BEP+GSH grubuna göre yüksek bulundu. BEP+GSH uygulanan grup ile kontrol grubunda morfolojik anomali oranı ve sperm DNA fragmantasyonu BEP grubuna göre oldukça düşük bulundu (p?0,001; p?0,001). BEP+GSH grubu ile kontrol grubunun serum testosteron seviyesi ve sperm sayısının BEP grubuna göre yüksek olduğu görüldü. Testislerde seminifer tübül epitel kalınlıklarının ve Johnsen skorlarının kontrol grubu ve BEP+GSH grubunda BEP grubuna göre daha kalın olduğu görüldü (p<0,000). Sonuç olarak GSH tedavisinin, BEP tedavisi alan sıçanlarda sperm sayısını, sperm morfolojik yapısını ve testis morfolojisini iyileştirmiş ve sperm DNA fragmantasyonunu azaltmış, bu nedenlerden dolayı kemoterapötiklerin sebep olduğu erkek infertilitesinde potansiyel iyileşme sağlamıştır.
Testicular cancer is one of the most common malignant tumors in young men of reproductive age (20-40 years). The combination of cis-platin-based chemotherapeutic agents and specific Bleomycin, Etoposide and cis-platin (BEP) used in its treatment increases survival and causes damage to healthy tissues. One of the important tissues in which it is damaged is testicular tissue and sperm cells. In this study, we investigated the protective effect of glutathione (GSH) application on sperm DNA integrity and testicular histomorphology damage caused by BEP treatment in rats. Twenty two-week-old male rats of reproductive age (n=24) were randomly divided into 3 groups as control, BEP and BEP+GSH, 8 rats in each group. The BEP group was administered intraperitoneally for 9 weeks, 3 cycles of 21 days each, according to the BEP doses determined in the preliminary study (0.083; 0.83; 0.17 mg/kg). Glutathione 200 mg/kg was administered to the BEP+GSH group on the 1st and 4th days of the week for 9 weeks, together with the chemotherapeutic treatment applied to the BEP group. In the control group, 0.9% NaCl was given intraperitoneally on the days when the other groups were treated with drugs. When the weight gains of the groups were compared, the weight gain of the BEP+GSH group was not significant compared to the weight gain of the BEP group (p=0.921). The increase in the control group was higher than the BEP group and BEP+GSH group (p?0.027, p?0.012). Similarly, left testis weights (p?0.017; p?0.003), left epididymis weights (p?0.029; p?0.037), right epididymis weights (p?0.002; p?0.004), testicular weight indices (p?0) of the control group ,0017; p?0.001) were higher than BEP group and BEP+GSH group. Morphological anomaly rate and sperm DNA fragmentation were found to be considerably lower in the BEP+GSH group and the control group compared to the BEP group (p?0.001; p?0.001). Serum testosterone level and sperm count of BEP+GSH group and control group were higher than BEP group. It was observed that seminiferous tubule epithelial thicknesses and Johnsen scores in testicles were thicker in the control group and BEP+GSH group compared to the BEP group (p<0.000). In conclusion, GSH treatment improved sperm count, sperm morphology, and testicular morphology in BEP-treated rats, and decreased sperm DNA fragmentation, thus potentially improving male infertility caused by chemotherapeutics.
Testicular cancer is one of the most common malignant tumors in young men of reproductive age (20-40 years). The combination of cis-platin-based chemotherapeutic agents and specific Bleomycin, Etoposide and cis-platin (BEP) used in its treatment increases survival and causes damage to healthy tissues. One of the important tissues in which it is damaged is testicular tissue and sperm cells. In this study, we investigated the protective effect of glutathione (GSH) application on sperm DNA integrity and testicular histomorphology damage caused by BEP treatment in rats. Twenty two-week-old male rats of reproductive age (n=24) were randomly divided into 3 groups as control, BEP and BEP+GSH, 8 rats in each group. The BEP group was administered intraperitoneally for 9 weeks, 3 cycles of 21 days each, according to the BEP doses determined in the preliminary study (0.083; 0.83; 0.17 mg/kg). Glutathione 200 mg/kg was administered to the BEP+GSH group on the 1st and 4th days of the week for 9 weeks, together with the chemotherapeutic treatment applied to the BEP group. In the control group, 0.9% NaCl was given intraperitoneally on the days when the other groups were treated with drugs. When the weight gains of the groups were compared, the weight gain of the BEP+GSH group was not significant compared to the weight gain of the BEP group (p=0.921). The increase in the control group was higher than the BEP group and BEP+GSH group (p?0.027, p?0.012). Similarly, left testis weights (p?0.017; p?0.003), left epididymis weights (p?0.029; p?0.037), right epididymis weights (p?0.002; p?0.004), testicular weight indices (p?0) of the control group ,0017; p?0.001) were higher than BEP group and BEP+GSH group. Morphological anomaly rate and sperm DNA fragmentation were found to be considerably lower in the BEP+GSH group and the control group compared to the BEP group (p?0.001; p?0.001). Serum testosterone level and sperm count of BEP+GSH group and control group were higher than BEP group. It was observed that seminiferous tubule epithelial thicknesses and Johnsen scores in testicles were thicker in the control group and BEP+GSH group compared to the BEP group (p<0.000). In conclusion, GSH treatment improved sperm count, sperm morphology, and testicular morphology in BEP-treated rats, and decreased sperm DNA fragmentation, thus potentially improving male infertility caused by chemotherapeutics.
Açıklama
Anahtar Kelimeler
Antineoplastik birleşik kemoterapi protokolleri, Spermatozoa, DNA fragmantasyonu, Antioksidanlar, Antineoplastic combined chemotherapy protocols, Spermatozoa, DNA fragmentation, Antioxidants
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Bayram, H. (2023). Bleomisin etoposid cis-platin tedavisi uygulanan sıçan modellemesinde oluşan sperm DNA fragmantasyonuna glutatyonun etkisi / The effect of glutathione on sperm DNA fragmentation in rat models of bleomycin etoposide cis-platin treatment. (Yayımlanmamış Doktora Lisans Tezi). Maltepe Üniversitesi, Lisansüstü Eğitim Enstitüsü, İstanbul.
