Protective mechanisms of icariin in methotrexate-induced renal damage: role of Nrf2/HO-1 and apoptosis reduction

Riya Mishra

doi:10.1515/jcim-2024-0431

Article

Protective mechanisms of icariin in methotrexate-induced renal damage: role of Nrf2/HO-1 and apoptosis reduction

Riya Mishra

Published/Copyright: February 20, 2025

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From the journal Journal of Complementary and Integrative Medicine Volume 22 Issue 2

Abstract

Objectives

Thus, the study was designed to assess the ability of ICA to ameliorate MTX-induced renal toxicity in rats and determine the pathogenetic pathways of oxidative stress, inflammation, and apoptosis.

Methods

Mtx renal toxicity was developed following an intraperitoneal administration of 20 mg/kg MTX. ICA was orally given at 100 mg/kg/day for two consecutive weeks. Experimental indicators included: biochemical renal function – BUN, SCr; and oxidative stress – SOD, GSH-Px, MDA. Other histological studies included immunohistochemical staining for Nrf2 and HO-1, QPCR of pro-inflammatory cytokines and biomarker of kidney injury, and TUNEL assay to assess the protective effects affiliated with ICA.

Results

In an animal model treated with MTX, renal damage was reflected by increased oxidative stress, inflammatory-borne cytokines, and apoptotic indices. ICA treatment ameliorated these effects to a great extent by reversing changes in antioxidant enzyme activities, suppressing lipid peroxidation and regulating the Nrf2/HO-1 pathway. This was evidenced by the decrease in pro-inflammatory and kidney injury genes in the ICA-treated groups but by significant histological ameliorations of kidney structure. TUNEL assay proved the decreased apoptotic index in kidney tissue.

Conclusions

These findings exhibited the therapeutic efficacy of ICA for attenuating renal injury from MTX and established that it mainly exerts its cytoprotective effects through the Nrf2/HO-1 pathway.

Keywords: methotrexate; icariin; renal toxicity; inflammation; apoptosis; oxidative stress

Corresponding author: Riya Mishra, School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India, E-mail: riyamishra1891@outlook.com

Research ethics: The Institutional Animal Ethical Committee of Siddhartha Institute of Pharmacy (Dehra Dun, India) approved this study (ref. SIP/IAEC.CLEAR/29/2023-24).
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: Authors state no conflict of interest.
Research funding: None declared.

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Received: 2024-11-27

Accepted: 2024-12-31

Published Online: 2025-02-20

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Articles in the same Issue

https://doi.org/10.1515/jcim-2024-0431

Keywords for this article

methotrexate; icariin; renal toxicity; inflammation; apoptosis; oxidative stress