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August 5, 2020Frontiers in PharmacologyOpen Access

Roxadustat (FG-4592) alleviated doxorubicin-induced cardiotoxicity in mice by protecting against cardiac dysfunction, apoptosis, and oxidative stress via upregulation of HIF-1α.

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Why the study?

Doxorubicin cardiotoxicity limits its clinical use, but the role of roxadustat (FG-4592) in doxorubicin-induced cardiotoxicity was unknown.

Does roxadustat (FG-4592) pretreatment prevent doxorubicin-induced cardiotoxicity in preclinical models?

Population

Mice, rat cardiomyocyte cells (H9c2), and HepG2 and MCF-7 cell lines

Comparison

DOX with FG-4592 pretreatment vs DOX alone, FG-4592 alone, and control

Design

In vivo animal and in vitro cell experimental study

Key result

Roxadustat (FG-4592) alleviated doxorubicin-induced cardiotoxicity in mice by protecting against cardiac dysfunction, apoptosis, and oxidative stress via upregulation of HIF-1α.

Authors

GLGuangfeng LongHCHongbing ChenMWMengying Wu

Discussion

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Member takes

Overview

May inform cardioprotection trials during chemotherapy; leaves open translation from murine models to patients.

Structured PICO

Does roxadustat (FG-4592) pretreatment prevent doxorubicin-induced cardiotoxicity in preclinical models?

P
Population
23 wild-type C57BL/6 mice (10-12 weeks old) subjected to doxorubicin-induced myocardial injury to evaluate the cardioprotective effects of FG-4592.
I
Intervention
Roxadustat (FG-4592) pretreatment (10 mg/kg/day intraperitoneally for 48 hours in vivo; 1-20 µM for 24-48 hours in vitro) prior to doxorubicin exposure.
C
Comparator
Vehicle/PBS control and doxorubicin alone (12.5 mg/kg single intraperitoneal injection in vivo; 1-10 µM in vitro).
O
Outcome
Cardiac function (LVEF and LVFS measured by echocardiography) and myocardial injury biomarkers (plasma LDH and CK-MB) at 7 days post-doxorubicin administration.surrogate

Roxadustat (FG-4592) protects against doxorubicin-induced cardiotoxicity in preclinical models by activating HIF-1a and its antiapoptotic and antioxidative target genes, without compromising doxorubicin's antitumor efficacy.

Limitations

  • Preclinical animal and in vitro models may not fully translate to human clinical outcomes
  • The exact mechanism of how FG-4592 modulates inflammation differently in various models remains unclear

Cite This Study

Long et al. (2020) studied Doxorubicin-induced cardiotoxicity (n=23). Roxadustat (FG-4592) vs. Doxorubicin alone was evaluated on Cardiac function (LVEF and LVFS) and cardiomyocyte apoptosis. Roxadustat (FG-4592) alleviated doxorubicin-induced cardiotoxicity in mice by protecting against cardiac dysfunction, apoptosis, and oxidative stress via upregulation of HIF-1α.

synapsesocial.com/papers/6a2016f535281a23f90de89ehttps://doi.org/10.3389/fphar.2020.01191
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Roxadustat improves diabetic myocardial injury by upregulating HIF-1α/UCP2 against oxidative stress2025 · 20 citations
  2. 2Pentoxifylline abrogates cardiotoxicity induced by the administration of a single high dose or multiple low doses of doxorubicin in rats2016 · 9 citations
  3. 3DiOHF Protects Against Doxorubicin-Induced Cardiotoxicity Through ERK1 Signaling Pathway2019 · 27 citations
  4. 4FoxO3 Activation Alleviates Doxorubicin-Induced Cardiomyopathy by Enhancing Autophagic Flux and Suppressing mTOR/ROS Signalling.2025 · 9 citations
  5. 5Abstract Fri069: The RXFP1 Agonist ML290 Protects Against Doxorubicin-induced Cardiomyocyte Injury <i>in vitro</i>2025