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

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

Abstract

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.

MeSH terms

  • Anastomosis, Surgical / adverse effects
  • Animals
  • Colon / surgery
  • Colorectal Neoplasms* / pathology
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Phenytoin* / metabolism
  • Phenytoin* / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Rectum / surgery
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • RNA, Messenger
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Phenytoin