Tissue content of metalloproteinase-9 and collagen in the colon with and without fecal stream after intervention with infliximab in rats subjected to Hartmann's surgery.

Antonio José Tiburcio Alves Junior,Mariane Grandi De Ávila,Carlos Augusto Real Martinez,Daniela Tiemi Sato,José Aires Pereira,Fernanda Aparecida Domingues

doi:10.1590/acb360401

Antonio José Tiburcio Alves Junior, Mariane Grandi De Ávila + Show 4 more

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https://doi.org/10.1590/acb360401

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Abstract

ABSTRACTPurposeQuantify the tissue content of metalloproteinase-9 (MMP-9) and collagen in colic mucosa with and without intestinal transit after infliximab administration in rats subjected to Hartmann’s surgery.MethodsTwenty-two rats underwent colon diversion by Hartmann’s surgery. Animals were maintained with intestinal bypass for 12 weeks to induce development of diversion colitis (DC). Afterwards, animals were divided into three groups: first group received subcutaneous application of saline solution (SS) 0.9%, while the remaining two groups received infliximab subcutaneously at doses of 5 or 10 mg·kg–1·week–1 for five consecutive weeks. After the intervention, animals were sacrificed, removing the segments with and without intestinal transit. Diversion colitis was diagnosed by histological study, and its intensity was determined by a validated inflammatory scale. Tissue expression of MMP-9 was assessed byimmunohistochemistry, while total collagen was assessed by histochemistry. Tissue content of both was measuredby computerized morphometry.ResultsColon segments without intestinal transit had a higher degree of inflammation, which improved in animals treated with infliximab. Collagen content was always lower in those without intestinal transit. There was an increase in the collagen content in the colon without transit in animals treated with infliximab, primarily at a dose of 10 mg·kg–1·week–1. There was an increase in the content of MMP-9 in the colon without fecal transit, and a reduction was observed in animals treated with infliximab, regardless of the dose used.ConclusionsApplication of infliximab reduces inflammation, increases the total collagen content and decreases the content of MMP-9 in the colon without intestinal transit.

Highlights

Ileostomy or colostomy, whether temporary or permanent, is a surgical procedure increasingly used for the management of several colorectal diseases, primarily represented by congenital anorectal anomalies, intestinal obstruction, intestinal inflammatory diseases (IBDs), complications of acute sigmoid diverticulitis, colorectal trauma, colorectal tumors and severe anoperineal infections[1]
Among the late complications related to the construction of a stoma after Hartmann’s surgery (HS), the chronic inflammatory process that affects the exclusive segments of fecal transit stands out
With intestinal transit deprivation, from the animals of the control group submitted to intervention with saline solution (SS) 0.9%, a reduction in the height and architecture of the crypts was observed, there was a breakdown in the distribution and alignment of the colic glands, a decrease in the thickness of the mucous layer and loss of continuity between colonocytes

Summary

Introduction

Whether temporary or permanent, is a surgical procedure increasingly used for the management of several colorectal diseases, primarily represented by congenital anorectal anomalies, intestinal obstruction, intestinal inflammatory diseases (IBDs), complications of acute sigmoid diverticulitis, colorectal trauma, colorectal tumors and severe anoperineal infections[1]. Among the late complications related to the construction of a stoma after Hartmann’s surgery (HS), the chronic inflammatory process that affects the exclusive segments of fecal transit stands out. A study using an experimental DC model showed that the deprivation of the main substrate for the normal metabolism of colic mucosa cells modifies the mitochondrial respiratory mechanisms, causing an increase in the production of free oxygen radicals (FOR)[5]. Free oxygen radicals are toxic substances to epithelial cells due to their high oxidative and proinflammatory power and they destroy the main defense mechanisms that form the epithelial barrier of the colic mucosa[5]. DC has been considered a disease caused by energy deficiency resulting from the lack of a regular supply of SCFAs to colic epithelial cells due to diversion of the fecal stream[6]

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