Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 177-186
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.177
Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine
Toshihide Ueda, Ryota Hokari, Masaaki Higashiyama, Yuichi Yasutake, Koji Maruta, Chie Kurihara, Kengo Tomita, Shunsuke Komoto, Yoshikiyo Okada, Chikako Watanabe, Shingo Usui, Shigeaki Nagao, Soichiro Miura
Toshihide Ueda, Ryota Hokari, Masaaki Higashiyama, Yuichi Yasutake, Koji Maruta, Chie Kurihara, Kengo Tomita, Shunsuke Komoto, Yoshikiyo Okada, Chikako Watanabe, Shingo Usui, Shigeaki Nagao, Soichiro Miura, Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan
Author contributions: All authors contributed to the manuscript.
Supported by National Defense Medical College, by Intractable Diseases, the Health and Labour Sciences Research Grants from Ministry of Health, Labour and Welfare and by Research for the similarity and difference in epidemiology, pathophysiology, diagnosis and treatment of rare intestinal refractory diseases and by a grant from the Smoking Research Foundation
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ryota Hokari, MD, Professor, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. ryota@ndmc.ac.jp
Telephone: +81-4-29951609 Fax: +81-4-29955201
Received: March 7, 2014
Peer-review started: March 7, 2014
First decision: April 2, 2014
Revised: May 11, 2014
Accepted: September 18, 2014
Article in press: September 19, 2014
Published online: January 7, 2015
Processing time: 306 Days and 2.2 Hours
Abstract

AIM: To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine.

METHODS: C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined.

RESULTS: In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05).

CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

Keywords: Non-steroidal anti-inflammatory drugs; Small intestine; Ulcer; Dietary fat; Adhesion molecules

Core tip: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently induce mucosal damage in the gastrointestinal tract. The recently developed techniques of capsule enteroscopy and double balloon enteroscopy have shown that NSAIDs cause ulcers in the small intestine (68%) more frequently than previously thought. Although proton pump inhibitors are key drugs for NSAIDs-induced gastropathy, proton pump inhibitors have no effect on NSAIDs-induced intestinal lesions and no drugs are currently available for the prevention and treatment of NSAIDs-induced intestinal lesions. In the present study, we showed the beneficial effect of an omega-6 PUFA-rich diet in NSAID-induced mucosal damage in the murine small intestine. This is a completely novel finding and is important not only in the clinical field, but also in preventive medicine.