Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2015; 21(38): 10853-10865
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10853
Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction
Yu-Meng Li, Hai-Bin Wang, Jin-Guang Zheng, Xiao-Dong Bai, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu
Yu-Meng Li, Jin-Guang Zheng, Zeng-Kai Zhao, Jing-Yuan Li, Sen Hu, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China
Yu-Meng Li, Medical School of Chinese PLA, Beijing 100853, China
Hai-Bin Wang, Department of Clinical Laboratory, The First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China
Jin-Guang Zheng, Xiao-Dong Bai, Department of Burn Surgery, the General Hospital of Armed Police Forces, Beijing 100039, China
Zeng-Kai Zhao, Beijing Tongzhou Hospital of Traditional Chinese Medicine, Beijing 101100, China
Author contributions: Li YM and Wang HB contributed equally to this study; Li YM, Zheng JG, Wang HB Bai XD and Hu S designed the research; Li YM, Zheng JG, Wang HB, Zhao ZK and Li JY performed the research; Li YM, Zheng JG and Hu S analyzed the data; Li YM, Wang HB, Bai XD and Hu S prepared and revised manuscript; all authors have read and approved the final manuscript.
Supported by National 11th Five-Year Plan of China for Military Medical Projects, No. 06Z055; and the National Natural Science Foundation of China, No. 81301607.
Institutional review board statement: The study was reviewed and approved by the First Hospital Affiliated to the Chinese PLA General Hospital Institutional Review Board.
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 Hospital Affiliated to the Chinese PLA General Hospital (IACUC protocol number: [11401500004432]). The experiments were conducted in compliance with the Guide for Care and Use of Laboratory Animals of the National Research Council, China.
Conflict-of-interest statement: All authors of this paper have read this manuscript; and no conflicts of interest exist in this study.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at [bs0425@163.com]. Participants gave informed consent for data sharing. Besides, no additional data are available.
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: Sen Hu, MD, PhD, Professor, Laboratory for Shock and Multiple Organ Dysfunction of Burns Institute, Key Research Laboratory of Tissue Repair and Regeneration of PLA, and Beijing Key Research Laboratory of Skin Injury and Repair Regeneration, the First Hospital Affiliated to the Chinese PLA General Hospital, No. 51 Fu Cheng Road, Beijing 100048, China. bs0425@163.com
Telephone: +86-10-66867397 Fax: +86-10-68989139
Received: June 7, 2015
Peer-review started: June 8, 2015
First decision: July 10, 2015
Revised: July 25, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: October 14, 2015
Processing time: 129 Days and 11.1 Hours
Abstract

AIM: To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome.

METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence.

RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs 81.1 ± 5.0 U/L, P < 0.05). DMSO significantly preserved ZO-1 protein expression and localization 24 h after zymosan administration. The TUNEL analysis indicated that the number of apoptotic intestinal cells in the ZS group was much higher than the ZD group (P < 0.05).

CONCLUSION: DMSO inhibited intestinal cytokines and protected against zymosan-induced gut barrier dysfunction.

Keywords: Dimethyl sulfoxide; Zymosan; Inflammation; Intestinal barrier; Tight junction

Core tip: We examined whether the administration of dimethyl sulfoxide (DMSO) inhibited zymosan-induced intestinal inflammation and barrier dysfunction to provide an experimental basis for the use of DMSO in protecting intestinal barrier function. We found that DMSO can inhibit intestinal cytokines and protect against zymosan-induced gut barrier dysfunction.