Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Aug 28, 2012; 18(32): 4278-4287
Published online Aug 28, 2012. doi: 10.3748/wjg.v18.i32.4278
Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis
Rodrigo Goulart Pacheco, Christiano Costa Esposito, Lucas CM Müller, Morgana TL Castelo-Branco, Leonardo Pereira Quintella, Vera Lucia A Chagas, Heitor Siffert P de Souza, Alberto Schanaider
Rodrigo Goulart Pacheco, Christiano Costa Esposito, Lucas CM Müller, Alberto Schanaider, Department of Surgery, Experimental Surgery Center, Surgical Sciences Postgraduate Program, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
Morgana TL Castelo-Branco, Laboratory of Cellular Immunology, Department of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
Leonardo Pereira Quintella, Vera Lucia A Chagas, Department of Pathology, Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
Heitor Siffert P de Souza, Department of Internal Medicine, Hospital Universitario Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
Author contributions: Pacheco RG designed the study, performed the surgical and endoscopic procedures, and was involved in acquisition and analysis of data and drafting of the manuscript; Esposito CC and Müller LCM performed the surgical and endoscopic procedures and animal care and was involved in acquisition and analysis of data; Castelo-Branco MTL contributed to study design, data acquisition and analysis, performed most of the laboratory tests, obtained technical and material support, and critical revision of the manuscript for important intellectual content; Quintella LP and Chagas VLA performed all histopathological tests, acquisition of data and analysis, interpretation of results, obtained technical or material support, and critical revision of the article; de Souza HSP and Schanaider A contributed to study conception and design, surgical procedures and supervision, data interpretation; obtained funding, administrative, technical, or material support, and drafting of the manuscript.
Supported by Grants from the Brazilian Research Council; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro
Correspondence to: Heitor Siffert P de Souza, MD, PhD, Department of Internal Medicine, Hospital Universitario Clementino Fraga Filho, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, Ilha do Fundao, Rio de Janeiro, RJ 21941-913, Brazil. heitor.souza@gmail.com
Telephone: +55-21-25622669 Fax: +55-21-25622669
Received: June 10, 2012
Revised: July 30, 2012
Accepted: August 3, 2012
Published online: August 28, 2012
Abstract

AIM: To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis.

METHODS: Wistar specific pathogen-free rats were submitted to a Hartmann’s end colostomy and treated with enemas containing glutamine, butyrate, or saline. Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure. Follow-up colonoscopy was performed every 4 wk for 12 wk. The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1β, tumor necrosis factor-alpha, and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay.

RESULTS: Colonoscopies of the diverted segment showed mucosa with hyperemia, increased number of vessels, bleeding and mucus discharge. Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P = 0.015; P = 0.001), the number of goblet cells (P = 0.021; P = 0.029), and the rate of apoptosis within the epithelium (P = 0.043; P = 0.011) to normal values. The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine.

CONCLUSION: The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

Keywords: Diversion colitis; Butyrate; Glutamine; Short-chain fatty acids; Cytokines