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

Year 2024, , 13 - 20, 18.03.2024

Büşra Candan , Malik Ejder Gülpak , Perihan Sezginer

https://doi.org/10.17343/sdutfd.1283354

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

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

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