Xing ZY, Zhang CJ, Liu LJ. Targeting both ferroptosis and pyroptosis may represent potential therapies for acute liver failure. World J Gastroenterol 2024; 30(33): 3791-3798 [PMID: 39351426 DOI: 10.3748/wjg.v30.i33.3791]
Corresponding Author of This Article
Li-Juan Liu, PhD, Lecturer, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, No. 185 Donghu Road, Wuhan 430071, Hubei Province, China. lijuanliu@whu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Editorial
Open-Access Policy of This Article
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/
World J Gastroenterol. Sep 7, 2024; 30(33): 3791-3798 Published online Sep 7, 2024. doi: 10.3748/wjg.v30.i33.3791
Targeting both ferroptosis and pyroptosis may represent potential therapies for acute liver failure
Zhong-Yuan Xing, Chuan-Jie Zhang, Li-Juan Liu
Zhong-Yuan Xing, Li-Juan Liu, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
Chuan-Jie Zhang, Department of Children Health Care, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430061, Hubei Province, China
Co-corresponding authors: Chuan-Jie Zhang and Li-Juan Liu.
Author contributions: Liu LJ and Zhang CJ designed the overall concept and outline of the manuscript; Xing ZY contributed to the discussion and design of the manuscript, as well as illustrations; Xing ZY, Zhang CJ, and Liu LJ contributed to the writing and editing of the manuscript and review of the literature; All authors have read and approved the final manuscript.
Supported byThe Hubei Provincial Natural Science Foundation of China, No. 2020CFB656.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose.
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: Li-Juan Liu, PhD, Lecturer, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, No. 185 Donghu Road, Wuhan 430071, Hubei Province, China. lijuanliu@whu.edu.cn
Received: March 18, 2024 Revised: August 10, 2024 Accepted: August 16, 2024 Published online: September 7, 2024 Processing time: 167 Days and 15.2 Hours
Abstract
In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.
Core Tip: Acute liver failure (ALF) is a life-threatening disease characterized by uncontrolled death of hepatocytes. Ferroptosis and pyroptosis are two recently discovered types of cell death that can occur simultaneously. However, their roles in ALF remain unclear. The findings show that these two cell death pathways work together to advance ALF and suggest that silent information regulator sirtuin 1 (SIRT1) and its downstream molecules could be potential therapeutics for ALF. Therefore, we will discuss the roles and crosstalk of ferroptosis and pyroptosis in ALF. Activation of SIRT1 and suppression of both cell death pathways may offer new insights into therapeutic targets for ALF.
