Ulus Travma Acil Cerrahi Derg. 2022; 28(9): 1214-1222 | DOI: 10.14744/tjtes.2022.03704

Investigation of the effects of post-operative intraperitoneal, oral, and rectal phenytoin administration on colorectal anastomosis in rats

Ali Duran¹, Ferhat Çay¹, Nelin Hacýoðlu², Esra Tokay², Feray Köçkar², Eren Altun³, Murat Baþbuð¹, Azad Gazi Þahin¹, Hasan Yaþar¹, Uður Mengeneci¹, Hüseyin Pülat^4
1Department of Surgery, Balýkesir University Faculty of Medicine, Balýkesir-Türkiye
²Department of Molecular Biology and Genetics, Balýkesir University Faculty of Sciences and Arts, Balýkesir-Türkiye
³Department of Pathology, University of Health Sciences, Baðcýlar Training and Research Hospital, Ýstanbul-Türkiye
⁴Department of General Surgery Clinic, Mersin City Hospital, Mersin-Türkiye

BACKGROUND: Anastomotic leakage is the most feared complication after colonic anastomosis. The purpose of the study is to determine the effects of phenytoin applied by different application routes, on the healing process of colorectal anastomoses.
METHODS: Wistar Albino rats were divided into Intraperitoneal Phenytoin Group, Oral Phenytoin Group (OAP), Rectal Phenytoin Group (RAP), and control groups. The molecular effect of phenytoin on the expression of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), fibroblast growth factor 2 (FGF2), and p53 genes was evaluated at mRNA and protein level. The effects of phenytoin on anastomotic bursting pressure analysis measured as well as pathohistological examinations.
RESULTS: There are statistically significant increase in anastomotic bursting pressure values between control and application groups. Inflammatory cell infiltration of all groups increased in the intestinal anastomosis region compared to control. Collagen scores were found to be significantly higher in the OAP and RAP groups compared to the control group. mRNA of TGF-ß and FGF2 expression increased in all routes of phenytoin applications.
CONCLUSION: Three different administration routes show considerably increase on the bursting pressure. Regarding the results of the expression of FGF2, TGF-β, p53, and VEGF genes, there is a significant increase FGF2 and TGF-β at mRNA and protein level in most administration routes.

Keywords: Colorectal anastomoses, epithelization; neovascularization; phenytoin; surgery.

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Sýçanlarda ameliyat sonrasý intraperitoneal, oral ve rektal fenitoin uygulamasýnýn kolorektal anastomoz üzerine etkilerinin araþtýrýlmasý

Ali Duran¹, Ferhat Çay¹, Nelin Hacýoðlu², Esra Tokay², Feray Köçkar², Eren Altun³, Murat Baþbuð¹, Azad Gazi Þahin¹, Hasan Yaþar¹, Uður Mengeneci¹, Hüseyin Pülat^4
1Balýkesir Üniversitesi Týp Fakültesi, Cerrahi Anabilim Dalý, Balýkesir
²Balýkesir Üniversitesi Fen-Edebiyat Fakültesi, Moleküler Biyoloji ve Genetik Bölümü, Balýkesir
³Saðlýk Bilimleri Üniversitesi, Baðcýlar Eðitim ve Araþtýrma Hastanesi, Patoloji Anabilim Dalý, Ýstanbul
⁴Mersin Þehir Hastanesi, Genel Cerrahi Kliniði, Mersin

AMAÇ: Anastomoz kaçaðý kolon anastomozlarýndan sonra en korkulan komplikasyondur. Bu çalýþmanýn amacý, farklý uygulama yollarýyla uygulanan fenitoinin kolorektal anastomozlarýn iyileþme sürecine etkisini belirlemektir.
GEREÇ VE YÖNTEM: Wistar Albino sýçanlar, Ýntraperitoneal Fenitoin Grubu (ÝAP), Oral Fenitoin Grubu (OAP), Rektal Fenitoin Grubu (RAP) ve kontrol gruplarýna ayrýldý. Fenitoinin VEGF, TGF-β, FGF2 ve p53 genlerinin ekspresyonu üzerindeki moleküler etkisi mRNA ve protein düzeyinde deðerlendirildi. Fenitoinin anastomoz patlama basýncý analizi üzerindeki etkilerinin yaný sýra patohistolojik incelemeler de ölçülmüþtür. BULGULAR: Kontrol ve uygulama gruplarý arasýnda anastomoz patlama basýncý deðerlerinde istatistiksel olarak anlamlý artýþ vardýr. Enflamatuvar hücre infiltrasyonu tüm gruplarda kontrole göre baðýrsak anastomoz bölgesinde artmýþtýr. Kollajen skorlarý OAP ve RAP gruplarýnda kontrol grubuna göre anlamlý derecede yüksek bulundu. TGF-ß’nin mRNA’sý ve FGF2 ekspresyonu, fenitoin uygulamalarýnýn tüm yollarýnda artmýþtýr.
TARTIÞMA: Üç farklý uygulama yolu, patlama basýncýnda önemli bir artýþ göstermektedir. FGF2, TGF-β, p53 ve VEGF genlerinin ekspresyon sonuçlarý ile ilgili olarak, çoðu uygulama yolunda mRNA ve protein seviyesinde FGF2 ve TGF-β’de önemli bir artýþ vardýr.

Anahtar Kelimeler: Cerrahi, epitelizasyon; fenitoin; kolorektal anastomoz; neovaskülarizasyon.

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