Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2017; 23(8): 1375-1386
Published online Feb 28, 2017. doi: 10.3748/wjg.v23.i8.1375
Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression
Nai-Ying Shen, Jian-Bin Bi, Jing-Yao Zhang, Si-Min Zhang, Jing-Xian Gu, Kai Qu, Chang Liu
Nai-Ying Shen, Jian-Bin Bi, Jing-Yao Zhang, Si-Min Zhang, Jing-Xian Gu, Kai Qu, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Nai-Ying Shen, Department of General Surgery, Shaanxi Nuclear Geology 215 Hospital, Xianyang 712000, Shaanxi Province, China
Author contributions: Shen NY, Bi JB, and Zhang JY contributed equally to the work; Shen NY, Bi JB and Zhang JY participated in the research design and in the writing of the paper; Zhang SM participated in literature collection and performed WB; Gu JX participated in statistical analysis and performed IHC; Qu K participated in statistical analysis; Liu C was involved in designing this research, writing and revising the paper.
Supported by the Project of Innovative Research Team for Key Science and Technology in Shaanxi Province, No. 2013KCJ-23; the Fundamental Research Funds for the Central Universities, No. 1191320114; and the National Natural Science Foundation of China, No. 81601672.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of The First Affiliated Hospital of Xi’an Jiaotong University (IACUC protocol number: XJTULAC2014-207).
Conflict-of-interest statement: We declare that there is no conflict of interest regarding the publication of this article.
Data sharing statement: The authors declare no competing financial interests.
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: Chang Liu, MD, PhD, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. liuchangdoctor@163.com
Telephone: +86-29-85323900 Fax: +86-29-85324642
Received: October 11, 2016
Peer-review started: October 13, 2016
First decision: December 2, 2016
Revised: December 20, 2016
Accepted: January 17, 2017
Article in press: January 17, 2017
Published online: February 28, 2017
Abstract
AIM

To investigate the therapeutic effect of hydrogen-rich water (HRW) on inflammatory bowel disease (IBD) and to explore the potential mechanisms involved.

METHODS

Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline (NS) intraperitoneally (ip); dextran sulfate sodium (DSS) group, in which the mice received NS ip (5 mL/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW (in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + ZnPP group, in which the mice received HRW (in the same volume as the NS treatment) and ZnPP [a heme oxygenase-1 (HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved.

RESULTS

The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d (P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group (P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group (P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group (P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1β compared with the DSS group (P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum (ER) stress, including p-eIF2α, ATF4, XBP1s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group (P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of ZnPP obviously reversed the protective role of HRW. In the DSS + HRW + ZnPP group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group (P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group.

CONCLUSION

HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.

Keywords: Hydrogen, Inflammatory bowel disease, Oxidative stress, Endoplasmic reticulum stress, Heme oxygenase-1

Core tip: Inflammatory bowel disease (IBD) is a chronic and relapsing disease primarily caused by the production of pro-inflammatory cytokines and leukocyte infiltration, resulting in structural and functional damage to the bowel. Hydrogen has obvious anti-oxidative and anti-inflammatory effects. We launched a study to investigate the protective role of hydrogen-rich water (HRW) on IBD in mice. The present study found that HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and endoplasmic reticulum stress and by up-regulating heme oxygenase-1 expression.