OYA SAYIN, SEREN GÜLŞEN GÜRGEN, NURCAN UMUR, AYŞE TUÇ YÜCEL, ECE ONUR

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

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

Anahtar Kelimeler:

Metoklopramid, Karaciğer, BrdU, PCNA, Ki-67

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

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,

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