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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2025; 31(35): 108139
Published online Sep 21, 2025. doi: 10.3748/wjg.v31.i35.108139
Published online Sep 21, 2025. doi: 10.3748/wjg.v31.i35.108139
Ambroxol mitigates cyclophosphamide-induced liver injury by suppressing TLR-4/NF-κB signaling and oxidative stress and upregulating cytoglobin, TXNRD1 and HMGB1
Reem S Alruhaimi, Department of Biology, College of Science, Princess Nourah bint Abdul
Emad H M Hassanein, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
Sulaiman M Alnasser, Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 52571, Saudi Arabia
Ahmad F Ahmeda, Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman 346, United Arab Emirates
Hanan S Althagafy, Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah 21589, Saudi Arabia
Omnia A M Abd El-Ghafar, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 62571, Egypt
Ayman M Mahmoud, Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M1 5GD, United Kingdom
Author contributions: Mahmoud AM and Hassanein EHM designed the study and analyzed the data; Alruhaimi RS, Hassanein EHM, Alnasser SM, Ahmeda AF, Althagafy HS, Abd El-Ghafar OAM, and Mahmoud AM performed the research and collected data; Mahmoud AM and Alruhaimi RS analyzed the data and wrote the manuscript; Mahmoud AM revised and edited the manuscript. All authors read and approved the final version.
Supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project Number (PNURSP2025R381), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Institutional animal care and use committee statement: All experimental protocols were approved by the Institutional Animal Ethics Committee of Al Azhar University, Egypt (Approval No. AZ-AS/PH-REC/3/25), and conducted in accordance with their guidelines.
Conflict-of-interest statement: All authors declare no conflict of interests in relation to the manuscript.
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: The manuscript contains all data supporting the reported results.
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: Ayman M Mahmoud, Professor, Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Dalton Building, Manchester M1 5GD, United Kingdom. a.mahmoud@mmu.ac.uk
Received: April 7, 2025
Revised: June 14, 2025
Accepted: August 6, 2025
Published online: September 21, 2025
Processing time: 165 Days and 19.3 Hours
Revised: June 14, 2025
Accepted: August 6, 2025
Published online: September 21, 2025
Processing time: 165 Days and 19.3 Hours
Core Tip
Core Tip: Cyclophosphamide (CP) is a cornerstone chemotherapeutic and immunosuppressive agent, but its hepatotoxicity limits its clinical utility. While oxidative stress and inflammation are known contributors to CP-induced liver injury, effective therapeutic strategies to counteract these effects remain limited. This study is the first to demonstrate that ambroxol exerts potent hepatoprotective effects against CP hepatotoxicity. Our findings not only elucidate the molecular mechanisms underlying the hepatoprotective effects of ambroxol but also position it as a promising adjunct therapy to mitigate CP hepatotoxicity. Given the lack of effective hepatoprotective agents against CP toxicity, this study has significant translational implications.