Gastroenterology

Gastroenterology

Volume 125, Issue 3, September 2003, Pages 775-785
Gastroenterology

Basic-alimentary tract
Dietary glycine prevents chemical-induced experimental colitis in the rat

https://doi.org/10.1016/S0016-5085(03)01067-9Get rights and content

Abstract

Background & Aims: In this study, the effect of dietary glycine on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) and dextran sulfate sodium (DSS) in the rat was evaluated. Methods: Male Wistar rats were fed a diet containing 5% glycine or casein as controls starting 3 days before experiments, and were given a single intracolonic injection of TNBS (50 mg/rat, dissolved in 50% ethanol). Similarly, some rats were given 3% DSS orally in drinking water for 5 days to induce colitis as a second model. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase (MPO) activity was measured. Further, mRNA and protein levels for interleukin (IL)-1β, tumor necrosis factor (TNF)-α, cytokine-induced neutrophil chemoattractant (CINC), and macrophage inflammatory protein (MIP)-2 were detected by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A diet containing glycine ameliorated diarrhea and body weight loss caused by TNBS, and improved both macroscopic and histologic scores of colitis significantly. TNBS-induced increases in MPO activities in the colonic tissue were blunted significantly in glycine-fed animals. Further, dietary glycine largely prevented increases in IL-1β and TNF-α in the colon 2 days after TNBS, and TNBS induction of CINC and MIP-2 in the colonic tissue also was abrogated by glycine. Importantly, the protective effect of glycine was significant even when TNBS colitis was once established. Moreover, dietary glycine also was preventive in a second, DSS-induced colitis model. Conclusions: Dietary glycine prevents chemical-induced colitis by inhibiting induction of inflammatory cytokines and chemokines. It is postulated that glycine may be useful for the treatment of inflammatory bowel diseases as an immunomodulating nutrient.

Section snippets

TNBS colitis model

Specific pathogen-free male Wistar rats weighing 200 g were obtained from Charles River Japan Inc. (Kanagawa, Japan), and were housed in a clean, temperature-controlled environment with a 12-hour light-dark cycle, and were given free access to regular laboratory chow diet and water for several days. All animals received humane care, and the study protocols were approved by the Committee of Laboratory Animals at Juntendo University School of Medicine according to institutional guidelines. Rats

The effect of glycine on symptomatic parameters and gross appearance of TNBS colitis

First, we observed the symptomatic parameters including body weight loss and diarrhea caused by colitis after a single intracolonic injection of TNBS. Both control diet— and glycine diet—fed rats without TNBS gained body weight, the average increment reaching 12.5 ± 2.5 g and 10.0 ± 2.7 g in 2 days, respectively (n = 10). The control diet—fed rats given a single intracolonic TNBS injection lost body weight, almost 13.0 ± 3.9 g in the same period (n = 10, P < 0.05 vs. control diet/saline by

Discussion

Glycine has been shown to be protective against various kinds of organ injuries including endotoxin-induced liver and lung injuries,23, 31 ischemia-reperfusion injury in the liver,22, 43 and chemical-induced renal damage.27, 28, 29 In the present study, we showed that pretreatment with dietary glycine prevents colitis induced by TNBS and DSS. This report proves the protective effect of glycine against inflammation in the colon. It is notable that induction of proinflammatory cytokines (IL-1β

Acknowledgements

The diet used in this study was a generous gift from Novartis Nutrition Corp. (St. Louis, MO). The authors are grateful to the late Dr. Ronald G. Thurman (Department of Pharmacology, University of North Carolina at Chapel Hill, NC) and Drs. Heinz Schneider and Norman A. Greenberg (Novartis Nutrition Corp.) for the arrangement of the diet. The authors also thank Megumi Masujima and Hanako Misawa for excellent technical assistance.

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    Supported in part by a grant-in-aid from the Ministry of Education, Science, Technology, and Culture of Japan.

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