What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin-induced cardiotoxicity. Intervention: Kaempferol (KP) vs. Doxorubicin (DOX) alone. Primary outcome: Cell viability and ferroptosis markers (mitochondrial ROS, lipid peroxidation).

May 13, 2025Redox Report25 citationsOpen Access

Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis

LZLin Zhang XLXiaorui Liu JWJuan Wang

Key Result

Kaempferol protected against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis via activation of the NRF2/SLC7A11/GPX4 pathway.

Structured PICO

Does Kaempferol prevent doxorubicin-induced myocardial damage in cardiomyocyte cell lines?

Population

H9c2 cells (embryonic rat cardiomyocyte cell line) and AC16 cells (adult human cardiomyocyte cell line) treated with doxorubicin to induce cardiomyopathy/ferroptosis

Intervention

Kaempferol (KP) 40, 80, and 160 μM for 24 hours

Comparator

Doxorubicin (DOX) 2 μM alone (model group) and untreated control cells

Outcome

Cell viability, mitochondrial ROS levels, lipid peroxidation, mitochondrial membrane potential, and expression of NRF2/SLC7A11/GPX4 pathway proteinssurrogate

Kaempferol protects against doxorubicin-induced cardiotoxicity in vitro by inhibiting mitochondrial ROS-dependent ferroptosis via the NRF2/SLC7A11/GPX4 pathway, suggesting its potential as a cardioprotective agent.

Limitations

In vivo validation in animal models is essential to confirm findings
Clinical translation is hindered by low oral bioavailability and extensive first-pass metabolism
The exact contribution of extracellular SOD activation to Kaempferol's effects remains unclear

Abstract

BACKGROUND: Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to explore underlying mechanisms of the cardioprotective effects of Kaempferol (KP) against DIC. METHODS: and lipid peroxidation were detected using JC-1, TMRE, Mito-SOX, Mito-Ferro Green and C11-BODIPY 581/591 probes. Furthermore, Western blot analysis measured the expression of key regulatory proteins, and NRF2-targeting siRNA was transfected into H9c2 cells. The nuclear translocation of NRF2 was assessed by immunofluorescence. RESULTS: , and regulating lipid metabolism. Mechanistically, Western blot analysis revealed that KP inhibited DOX-induced ferroptosis by activating NRF2/SLC7A11/GPX4 axis. Moreover, KP promoted the accumulation and nuclear translocation of NRF2 protein. CONCLUSION: These findings demonstrated that KP protected against DOX-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis. This provides novel insights into KP as a promising drug candidate for cardioprotection.

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