Kelleni MT, Abdelzaher WY, Adly M, Attya ME, Fawzy MA, Ibrahim MA. Targeting sirtuin 1/nuclear factor erythroid 2-related factor 2/tumor necrosis factor-α pathway to modulate hepatic ischemia reperfusion-induced injury. World J Hepatol 2025; 17(12): 110733 [DOI: 10.4254/wjh.v17.i12.110733]
Corresponding Author of This Article
Mina Thabet Kelleni, MD, PhD, Assistant Professor, Department of Medical Pharmacology, College of Medicine, Minia University, Main Road Shalaby Land, Minia 61519, Egypt. mina.kelleni@mu.edu.eg
Research Domain of This Article
Pharmacology & Pharmacy
Article-Type of This Article
Basic Study
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/
Mina Thabet Kelleni, Walaa Yehia Abdelzaher, Marly Adly, Mina Ezzat Attya, Michael A Fawzy, Mohamed Abdellah Ibrahim
Mina Thabet Kelleni, Walaa Yehia Abdelzaher, Marly Adly, Mohamed Abdellah Ibrahim, Department of Medical Pharmacology, College of Medicine, Minia University, Minia 61519, Egypt
Walaa Yehia Abdelzaher, Department of Pharmacology, Faculty of Oral and Dental Medicine, Lotus University, Minia 61768, Egypt
Mina Ezzat Attya, Department of Pathology, Minia University, Minia 61519, Egypt
Michael A Fawzy, Department of Biochemistry-Faculty of Pharmacy, Minia University, Minia 61519, Egypt
Author contributions: Kelleni MT, Abdelzaher WY, Adly M, and Ibrahim MA were responsible for conceptualization of the concept, performing the experiments, writing, and revising the manuscript; Attya ME performed and wrote the histopathological and immunohistochemical examination; Fawzy MA performed and wrote the western blotting. All authors read, revised, and approved the manuscript.
Institutional review board statement: Permission was received from the Study Ethics Committee of the Faculty of Medicine, Minia University (No. 585/2023).
Institutional animal care and use committee statement: The National Institutes of Health’s guide for the care and use of laboratory animals was followed during the research. All methods were done in accordance with the relevant ethical guidelines and regulations.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All the necessary data are included in the manuscript. Any further data will be made available upon a reasonable request.
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: Mina Thabet Kelleni, MD, PhD, Assistant Professor, Department of Medical Pharmacology, College of Medicine, Minia University, Main Road Shalaby Land, Minia 61519, Egypt. mina.kelleni@mu.edu.eg
Received: June 13, 2025 Revised: July 24, 2025 Accepted: November 7, 2025 Published online: December 27, 2025 Processing time: 196 Days and 10.7 Hours
Core Tip
Core Tip: This study demonstrates that aprepitant, a neurokinin-1 receptor antagonist, exerts hepatoprotective effects in a rat model of hepatic ischemia reperfusion by modulating the sirtuin 1/nuclear factor erythroid-2-related factor 2/tumor necrosis factor alpha signaling pathway. Aprepitant significantly reduced hepatic enzyme elevation, oxidative stress parameters, inflammatory cytokines, and apoptosis markers, while enhancing the pluripotent capacity of sirtuin 1/nuclear factor erythroid-2-related factor 2 expression, highlighting its potential as a therapeutic agent to mitigate HIR-induced liver injury during major liver surgeries, as well as highlighting the significant therapeutic pharmacological potential while targeting this pathway by other current and future drugs.
