UTERUS DOKUSU ÜZERİNE DOKSORUBİSİN VE AGOMELATİN’İN ETKİLERİ: HİSTOPATOLOJİK BİR ÇALIŞMA

Abstract

Amaç Antrasiklin bir antibiyotik olan doksorubisin (DOX) çeşitli kanser tiplerinin tedavilerinde kullanılan bir ilaçtır. Apoptozis, inflamasyon, serbest radikal oluşumu ve mitokondriyal DNA hasarı sonucunda akciğer, böbrek, kalp, karaciğer, beyin ve over gibi organlarda hasara neden olur. Agomelatin (AGO) güçlü bir antioksidan olan melatoninin agonistidir. AGO’nun; kalp, beyin, böbrek, karaciğer ve over dokularında anti-inflamatuar ve antioksidan etkinliği çeşitli çalışmalarla ortaya konulmuştur. Bu çalışmada, DOX’un uterus dokusunda neden olduğu toksisite üzerine AGO’nun koruyucu etkisini belirlemeyi amaçladık. Gereç ve Yöntem Bu çalışma her grupta 8 dişi sıçan olacak şekilde toplamda 32 sıçan üzerinde gerçekleştirildi. Deney grupları; Kontrol, DOX, DOX+AGO20 ve DOX+AGO40 şeklinde 4 gruptan oluşturuldu. Kontrol grubunda yer alan sıçanlara 12 gün boyunca günde tek doz 1 ml serum fizyolojik (SF) oral gavajla ve sadece 12. gün intraperitoneal olarak verildi. DOX grubundaki hayvanlara 12 gün boyunca her gün oral gavaj yöntemiyle 1 ml SF ve 12.günde intraperitoneal (i.p.) olarak tek doz 40 mg/kg DOX verildi. DOX+AGO20 grubundaki hayvanlara 12 gün boyunca her gün oral gavaj yöntemiyle 20 mg/kg AGO ve 12.gün i.p. olarak 40 mg/kg DOX verildi. DOX+AGO40 grubunda yer alan hayvanlara da 12 gün boyunca her gün oral gavaj tekniğiyle 40 mg/kg AGO ve 12.günde 40 mg/kg i.p. olarak DOX verildi. Bulgular Yapılan histopatolojik işlemler ve incelemeler sonucunda DOX grubuna ait uterus dokularında oluşan hasarlanmaya karşı, DOX+ AGO20 ve DOX+AGO40 kombine uygulanan gruplarda hasarın azaldığı görülmüştür. İmmün boyamalar (E-kadherin ve eNOS) sonucunda da DOX grubunda boyanma şiddetinin fazla, DOX+ AGO20 ve DOX+AGO40 kombine gruplarda ise daha az olduğu tespit edilmiştir. Sonuç Sonuç olarak DOX’un uterus dokusunda oluşturduğu hasara karşı AGO’nun koruyucu etkisi olduğunu düşünmekteyiz.

Keywords

• Uterus
• Doksorubisin
• Agomelatin
• Histopatoloji

THE EFFECTS OF DOXORUBICIN AND AGOMELATIN ON UTERUS TISSUE: A HISTOPATHOLOGICAL STUDY

Abstract

Objective Doxorubicin (DOX), an anthracycline antibiotic, is a drug used in the treatment of various types of cancer. It causes damage to organs such as lung, kidney, heart, liver, brain and ovary as a result of apoptosis, inflammation, free radical formation, mitochondrial DNA damage. Agomelatine (AGO) is an agonist of the powerful antioxidant melatonin. Anti-inflammatory and antioxidant activity of AGO in heart, brain, kidney, liver and ovary tissues has been demonstrated by various studies. In this study, we aimed to determine the protective effect of AGO on the toxicity of doxorubicin in the uterine tissue. Material and Method This study was carried out on 32 rats, 8 female rats in each group. Experimental groups: Control was formed from 4 groups as DOX, DOX+AGO20 and DOX+AGO40. The rats in the control group were given 1 ml of saline (SF) once a day by oral gavage for 12 days and intraperitoneally only on the 12th day. The animals in the DOX group were given 1 ml of saline by oral gavage every day for 12 days and a single dose of 40 mg/kg DOX intraperitoneally (i.p.) on the 12th day. Animals in the DOX+AGO20 group were given 20 mg/kg AGO by oral gavage method every day for 12 days. On the 12th day, i.p. 40 mg/kg DOX was given. Animals in the DOX+AGO40 group were given 40 mg/kg AGO by oral gavage method every day for 12 days. On the 12th day, i.p. 40 mg/kg DOX was given. Results As a result of the histopathological procedures and examinations, it was observed that the damage to the uterine tissues of the DOX group was reduced in the groups that were administered DOX+ AGO20 and DOX+AGO40 combined. As a result of immunostaining (E-cadherin and eNOS), it was determined that the staining intensity was higher in the DOX group and less in the DOX+ AGO20 and DOX+AGO40 combined groups. Conslusion As a result, we think that AGO has a protective effect against the damage caused by DOX in the uterine tissue.

Keywords

• Uterus
• Doxorubicin
• Agomelatine
• Histopathology

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