Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2023; 29(5): 867-878
Published online Feb 7, 2023. doi: 10.3748/wjg.v29.i5.867
Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model
Hitoshi Masuo, Akira Shimizu, Hiroaki Motoyama, Koji Kubota, Tsuyoshi Notake, Takahiro Yoshizawa, Kiyotaka Hosoda, Koya Yasukawa, Akira Kobayashi, Yuji Soejima
Hitoshi Masuo, Akira Shimizu, Hiroaki Motoyama, Koji Kubota, Tsuyoshi Notake, Takahiro Yoshizawa, Kiyotaka Hosoda, Koya Yasukawa, Akira Kobayashi, Yuji Soejima, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Author contributions: Masuo H, Motoyama H, Yoshizawa T, Hosoda K, and Yasukawa K contributed to the acquisition and analysis of experimental data and drafting of the manuscript; Shimizu A, Kubota K, Notake T, Kobayashi A, and Soejima Y contributed to the conception and design of the study and made critical revisions related to the important intellectual content of the manuscript; and all authors have provided final approval for the version of the manuscript for submission.
Supported by the JSPS KAKENHI, JP17K10664.
Institutional animal care and use committee statement: Based on national and institutional regulations and guidelines, all procedures for animal experiments were reviewed by the Committee for Animal Experiments and approved by the President of Shinshu University (Approval numbers 270018 and 019067).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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: Akira Shimizu, MD, PhD, Associate Professor, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan. ashimizu@shinshu-u.ac.jp
Received: October 29, 2022
Peer-review started: October 29, 2022
First decision: November 30, 2022
Revised: December 7, 2022
Accepted: January 11, 2023
Article in press: January 11, 2023
Published online: February 7, 2023
ARTICLE HIGHLIGHTS
Research background

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has already been clinically applied in various countries. Although it has been reported that ALPPS offers faster and larger liver regeneration compared to portal vein embolization (PVE), the mechanism of this phenomenon is still unclear.

Research motivation

The aim of this study was to investigate the underlying mechanism of rapid liver regeneration after ALPPS focusing on inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activation.

Research objectives

Activation of eNOS was considered one of key points on mechanism of rapid liver regeneration after ALPPS.

Research methods

Liver regeneration was compared between the rat portal vein ligation (PVL) model and the rat ALPPS model. In addition, impact of administration of gadolinium chloride (GdCl3, Kupffer cell inhibitor), NG-nitro-arginine methyl ester (L-NAME, NOS inhibitor), and molsidomine (NO enhancer) on liver regeneration after PVL and/or ALPPS.

Research results

Administration of GdCl3 before ALPPS provided no significant negative influence of liver regeneration after ALPPS. Administration of L-NAME before ALPPS suppressed liver regeneration after ALPPS, while administration of molsidomine before PVL accerelated liver regeneration after PVL as well as ALPPS.

Research conclusions

ALPPS is an alternative to PVE for reducing posthepatectomy liver failure after major hepatectomy.

Research perspectives

Combination of NO-producing agents and less invasive procedure can be an alternative to ALPPS procedure in the future.