Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2021; 27(48): 8323-8342
Published online Dec 28, 2021. doi: 10.3748/wjg.v27.i48.8323
Dual therapy with zinc acetate and rifaximin prevents from ethanol-induced liver fibrosis by maintaining intestinal barrier integrity
Yuki Fujimoto, Kosuke Kaji, Norihisa Nishimura, Masahide Enomoto, Koji Murata, Soichi Takeda, Hiroaki Takaya, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Hitoshi Yoshiji
Yuki Fujimoto, Kosuke Kaji, Norihisa Nishimura, Masahide Enomoto, Koji Murata, Soichi Takeda, Hiroaki Takaya, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Hitoshi Yoshiji, Department of Gastroenterology, Nara Medical University, Kashihara 6348521, Nara, Japan
Author contributions: Fujimoto Y and Kaji K designed the research study; Fujimoto Y, Kaji K, Nishimura N, Enomoto M, Murata K, Takeda S, Takaya H and Kawaratani H performed the research; Moriya K, Namisaki T and Akahane T offered new reagents, analytic tools and material support; Fujimoto Y and Kaji K analyzed the data and wrote the manuscript; Yoshiji H supervised this study; All authors have read and approve the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Institutional review board of Nara Medical University, Kashihara, Japan (authorization numbers: 12734).
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: No additional data are available.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kosuke Kaji, MD, PhD, Doctor, Lecturer, Senior Researcher, Department of Gastroenterology, Nara Medical University, 840, Shijo-cho, Kashihara 6348521, Nara, Japan. kajik@naramed-u.ac.jp
Received: July 6, 2021
Peer-review started: July 6, 2021
First decision: July 26, 2021
Revised: July 6, 2021
Accepted: December 10, 2021
Article in press: December 22, 2021
Published online: December 28, 2021
Processing time: 171 Days and 5.2 Hours
Core Tip

Core Tip: Gut-derived lipopolysaccharide dictates the progression of alcoholic liver disease (ALD) hence the maintenance of intestinal barrier integrity has attracted attention for the treatment of ALD. This study elucidates the preventive effect of combined zinc supplementation and rifaximin from ALD-related liver fibrosis induced by ethanol plus carbon tetrachloride in mice. This effect is involved in the multifaceted regulatory functions that maintain intestinal barrier integrity and reduce hepatic lipopolysaccharide exposure, thereby, leading to Kupffer cell expansion and hepatic stellate cell activation by inhibiting the toll-like receptor 4 pathway, highlighting that this regimen may represent a potential novel strategy against ALD-related liver fibrosis.