AN EXAMINATION OF THE EFFECT OF METOCLOPRAMIDE ON PROLIFERATION SIGNAL MOLECULES IN NEWBORN LIVER TISSUE

Year 2018, Volume: 32 Issue: 2, 69 - 76, 27.08.2018

Oya Sayın Seren Gülşen Gürgen Nurcan Umur Ayşe Tuç Yücel Ece Onur

https://doi.org/10.5505/deutfd.2018.25338

Abstract

Objective:
Metoclopramide (MCP) is a drug widely used in nausea and vomiting (in the
presence of symptoms / complaints) and recently during lactation period. There
are no studies at the molecular level in the literature concerning potential
side-effects in the newborn caused by the use of MCP during breastfeeding. The
purpose of this study was to investigate the potential proliferative changes in
newborn liver tissue caused by MCP.

Material and Method: 18 young adult female Wistar albino rats that had
recently given birth, together with their pups, were divided into 3 groups;
healthy control, administered a low dose of MCP, and administered a high dose
of MCP.

The
experiment continued throughout the lactation period. Pups’ hepatic tissues
were removed under light microscopy at the end of the 21st day.
5-bromo-2-deoxyuridine (BrdU), Ki-67 and proliferating cell nuclear antigen
(PCNA) were used in immunohistochemical staining. BrdU and Ki-67 levels in the
tissue homogenate were assessed using the ELISA method.

Results: BrdU, PCNA
and Ki-67 immunoreactivities in hepatocytes around the central vein of control
group were moderate whereas BrdU, PCNA and Ki-67 immunoreactivities were significantly
increased in the low-dose group and in the high-dose MCP groups compared to the
control group. In tissue homogenates, Brdu and Ki-67 ELISA levels were observed
to be significantly increased in low-dose and high- dose MCP groups compared to
the control group.

Conclusion:
In our study, increased BrdU, PCNA and Ki-67 immunreactions in livers in both
the low- and the high-dose MCP groups show that this agent affected DNA
synthesis and it may also cause an excessive proliferation index. 

Keywords

Metoclopramide, Liver, BrdU, PCNA, Ki-67

Metoklopramid’in Yenidoğan Karaciğer Dokusunda Proliferasyon Sinyal Molekülleri Üzerine Etkisinin İncelenmesi

Abstract

Amaç:
Klinikte metoklopramid (MCP) bulantı, kusma (semptomu/yakınması)
varlığında ve son yıllarda laktasyon döneminde yaygın olarak kullanılan
ilaçtır. MCP’nin emzirme döneminde kullanılmasının yeni doğanda neden
olabileceği yan etkilerle ilgili literatürde moleküler düzeyde bir çalışma
bulunmamaktadır. Çalışmamızda MCP’nin yenidoğan karaciğer dokusunda neden
olabileceği proliferatif değişikliklerin incelenmesi amaçlanmıştır.

Gereç
ve Yöntem: Çalışmada 18 adet dişi Wistar-albino yeni doğum yapmış
sıçanlar yavruları ile birlikte 3 gruba ayrıldı. Sağlıklı kontrol, düşük doz
MCP uygulanan grup, yüksek doz MCP uygulanan grup. Deney laktasyon dönemi
boyunca devam etti ve 21 gün sonunda yavruların karaciğer dokusunda
immunohistokimyasal boyama ile 5-Bromo-2-Deoksiuridin (BrdU), Ki-67 ve
prolifere hücre nükleer antigeni (PCNA); doku homojenatında ELISA ile  BrdU ve Ki-67 düzeyleri değerlendirildi.

Bulgular:
Kontrol grubunun santral ven çevresindeki hepatositlerde BrdU, PCNA ve Ki-67
immunreaktiviteleri orta şiddette iken; düşük ve yüksek doz metoklopramid
gruplarında kontrole göre istatistiksel anlamlı arttığı saptandı. Doku
homojenatları BrdU ve Ki-67 düzeylerinde, hem düşük hem de yüksek doz MCP
gruplarında kontrole göre istatistiksel olarak anlamlı artış gözlendi.

Sonuç:
Çalışmamızda hem düşük hem de yüksek doz MCP gruplarında, BrdU, PCNA ve Ki-67
immunreaksiyonun artması bu ajanın, hücrede DNA sentezini etkilediğini
göstermektedir. Bu da aşırı proliferasyon indeksine neden olabilmektedir

Keywords

Metoklopramid, Karaciğer, BrdU, PCNA, Ki-67

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