95% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Renal Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1506482
This article is part of the Research Topic Cell Death in Kidney Diseases: Novel Biomarkers, Mechanisms, and Therapeutic Strategies View all 11 articles
5-Methoxytryptophan Ameliorates Renal Ischemia/Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress-mediated Apoptosis through the Nrf2/HO-1 Pathway
Provisionally accepted- The Affiliated Hospital of Qingdao University, Qingdao, China
Background: Renal ischemia/reperfusion (I/R) injury is a prevalent clinical complication characterized by high incidence and mortality rates. The endogenous metabolite, 5-Methoxytryptophan (5-MTP), derived from tryptophan, possesses anti-inflammatory and antioxidant properties. However, its role in renal I/R injury remains unclear. In this study, we investigated whether 5-MTP could protect the kidney from I/R injury by ameliorating endoplasmic reticulum stress (ERS)-mediated apoptosis through the Nrf2/HO-1 pathway. Methods and Results: We established models to examine renal I/R injury in C57BL/6J mice with bilateral renal pedicles clamped and HK-2 cells subjected to hypoxia/reoxygenation (H/R). The administration of 5-MTP improved renal tissue damage and kidney dysfunction impairment and reduced inflammation and oxidative stress. Moreover, 5-MTP attenuated ERS and ERS-mediated apoptosis, while upregulating Nrf2 and HO-1 expression. Additionally, Nrf2-deficient mice and cells were used to determine whether the Nrf2/HO-1 pathway was involved in the role of 5-MTP in alleviating ERS-mediated apoptosis. Nrf2 deficiency led to a partial reduction in the suppressive effects of 5-MTP on inflammation, oxidative stress, and ERS-mediated apoptosis. Conclusions: Our findings suggest that 5-MTP alleviates renal I/R injury by inhibiting ERS-related apoptosis via the Nrf2/HO-1 pathway.1.
Keywords: 5-Methoxytryptophan, ischemia-reperfusion injury, Endoplasmic Reticulum Stress, Apoptosis, Nuclear factor erythroid-2 related factor 2, Heme Oxygenase-1
Received: 05 Oct 2024; Accepted: 02 Apr 2025.
Copyright: © 2025 Li, Yang, Zhang, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiangkun Li, The Affiliated Hospital of Qingdao University, Qingdao, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.