Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Dec 27, 2022; 14(12): 1329-1339
Published online Dec 27, 2022. doi: 10.4240/wjgs.v14.i12.1329
Hydrogen gas and preservation of intestinal stem cells in mesenteric ischemia and reperfusion
Ryo Yamamoto, Sayuri Suzuki, Koichiro Homma, Shintaro Yamaguchi, Tomohisa Sujino, Junichi Sasaki
Ryo Yamamoto, Sayuri Suzuki, Koichiro Homma, Junichi Sasaki, Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo 1608582, Japan
Shintaro Yamaguchi, Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 1608582, Japan
Tomohisa Sujino, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 1608582, Japan
Author contributions: Yamamoto R, Suzuki S, Homma K, Yamaguchi S, and Sujino T designed the experiment; Yamamoto R, Suzuki S, and Homma K performed the experiment and analyzed the data; Sasaki J supervised the experiment; Yamamoto R and Suzuki S wrote the original manuscript; Yamamoto R, Suzuki S, and Homma K revised the manuscript; all authors reviewed the manuscript.
Institutional animal care and use committee statement: The protocol used in this study was approved by the Research Council and Animal Care and Use Committee of the Research Institute of Keio University in Tokyo, Japan (approval number 21013-0) and was performed in accordance with the guidelines for the care and use of laboratory animals established by the Japanese Pharmacological Society and the National Institutes of Health.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at homma@keio.jp.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Koichiro Homma, MD, PhD, Assistant Professor, Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 1608582, Japan. homma@keio.jp
Received: August 25, 2022
Peer-review started: August 25, 2022
First decision: September 2, 2022
Revised: September 11, 2022
Accepted: November 7, 2022
Article in press: November 7, 2022
Published online: December 27, 2022
ARTICLE HIGHLIGHTS
Research background

Mesenteric ischemia introduces unfavorable clinical outcomes particularly when bowel necrosis is diagnosed, and it can happen even after revascularization. However, promising treatment has not been developed to prevent bowel necrosis after revascularization.

Research motivation

Hydrogen gas inhalation has showed tissue preserving effects for several ischemia-reperfusion injuries by reducing reactive oxygen species (ROS) in various animal and clinical studies. In addition, the safety of hydrogen gas was shown by clinical studies that examined the efficacy of hydrogen on myocardial infarction and post-cardiac arrest syndrome. Therefore, hydrogen gas for mesenteric ischemia can be a novel noninvasive treatment.

Research objectives

This study aimed to clarify the favorable effects of hydrogen gas inhalation for mesenteric ischemia and reperfusion. We hypothesized that the degree of tissue damage in the intestines following ischemia and reperfusion would be mitigated by continuous initiation of 3% hydrogen gas.

Research methods

Rats were allocated to three groups: ischemia (control 1) that underwent 60-min occlusion of mesenteric artery by clamping under laparotomy, reperfusion (control 2) that underwent the ischemia procedure and 60-min release of occlusion, and hydrogen that underwent the ischemia and reperfusion under 0.3% hydrogen gas inhalation at a rate of 0.2 L/min. Then, the tissue damages at the ileum were histologically evaluated, using immunostaining against caspase-3, 8-hydroxy-2'-deoxyguanosine, and leucine-rich repeat-containing G-protein-coupled 5 (LGR5). Several mRNA, including LGR5, were quantitatively measured with RT-PCR.

Research results

The reperfusion procedure introduced intestinal tissue destruction, which was mitigated by hydrogen gas inhalation. In addition, the intestinal tissue injury by the reperfusion involved intestinal stem cell that was marked by LGR5, whereas the ischemia without reperfusion did not affect the stem cell. The expression of LGR5 was significantly lower in the reperfusion group than in the ischemia group, whereas the expression of LGR5 was higher in the hydrogen group than in the reperfusion group.

Research conclusions

This study reported on the tissue-protective effects of continuous hydrogen gas inhalation in the ischemia and reperfusion injury at the intestine. The target cells of hydrogen might be intestinal stem cells that are injured by excessive ROS caused by reperfusion following ischemia.

Research perspectives

Hydrogen may reduce ROS in other tissues in addition to the intestinal mucosa, which should be examined in the future study. Moreover, the mechanisms of the reduction of ROS toxicity by hydrogen should be revealed to validate the hydrogen as a noninvasive novel treatment.