Abstract

To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1β, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1β, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs.

Highlights

  • Anastomotic dehiscence is the most severe complication of colorectal surgery, occurring in 2.4 to 3.8% of the cases[1].Different parameters can be used to analyze the healing process of anastomosis

  • Effects of metoclopramide on non-septic rats There were no deaths in either group on the 3rd or 7th postoperative day (POD)

  • On the 7th POD, one animal in the treated subgroup (NS7) had anastomotic dehiscence blocked by adjacent organs, which was noticed only after opening the surgical specimen

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Summary

Introduction

Anastomotic dehiscence is the most severe complication of colorectal surgery, occurring in 2.4 to 3.8% of the cases[1].Different parameters can be used to analyze the healing process of anastomosis. An increased presence of active forms of MMPs may lead to localized matrix degradation and a transient loss of strength in the anastomosed segment, leading to anastomotic dehiscence[3]. Another important healing parameter is cytokine expression in the anastomotic area. Cytokines and chemokines interact to determine the strength of the inflammatory response and the extent of subsequent adhesion formation[8]. These interactions are complex and produce both proand anti-inflammatory cytokines. Pro-inflammatory cytokines include tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-8, while anti-inflammatory molecules include IL-4 and IL10

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