ArticleOxidative medicine and cellular longevity2014
Nrf2 deficiency exaggerates doxorubicin-induced cardiotoxicity and cardiac dysfunction.
Article in Oxidative medicine and cellular longevity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 178 citations in OpenAlex.
- Vardenafil Alleviates Doxorubicin-Induced Cardiotoxicity Associated with Restoration of the AMPK/SIRT1 Signaling Pathway.Biomedicines · 2026Article
- Protective Effects of Vitamin D Against Doxorubicin Chemotherapy-Induced Hepatotoxicity in Wistar Albino Rats: Evidence fromNutrients · 2026Article
- Transcriptomic biomarkers related to cardiac disease in childhood cancer survivors: a case-control study.European heart journal · 2026Article
- The emerging role of Nrf2 in heart failure: From cardioprotection to therapeutic approaches.ESC heart failure · 2025Review
- Potential Mechanisms of Exercise-Mediated Ferroptosis Regulation in Central Nervous System Diseases.Molecular neurobiology · 2025Review
- AICAr Inhibition of cardiomyocyte autophagy promotes p62-dependent NRF2 expression and protection against doxorubicin toxicity.Cellular and molecular life sciences : CMLS · 2025Article
- Methylene Blue Mitigates Doxorubicin-Induced Cardiotoxicity via KEAP1/NRF2/GPX-4/Caspase3 Modulation.International journal of molecular sciences · 2025Article
- Article
- Taxifolin Protects Against 5-Fluorouracil-Induced Cardiotoxicity in Mice Through Mitigating Oxidative Stress, Inflammation, and Apoptosis: Possible Involvement of Sirt1/Nrf2/HO-1 Signaling.Cardiovascular toxicology · 2025Article
- Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity.Cardiovascular toxicology · 2025Review
- Yellow Wine Polyphenolic Compounds protect against myocardial ischemia-reperfusion injury in rats by activating Nrf2 nuclear translocation to regulate the balance of mitochondrial fission and fusion.Frontiers in cardiovascular medicine · 2025Article
- The protective effect and mechanism of dexmedetomidine in inhibiting ferroptosis.Frontiers in pharmacology · 2025Review
- Sulforaphane regulates AngII-induced podocyte oxidative stress injury through the Nrf2-Keap1/ho-1/ROS pathway.Renal failure · 2024Article
- Article
- Prevention and treatment of anthracycline-induced cardiotoxicity: A bibliometric analysis of the years 2000-2023.Heliyon · 2024Article
- Novel molecular mechanisms of doxorubicin cardiotoxicity: latest leading-edge advances and clinical implications.Molecular and cellular biochemistry · 2024Review
- Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy.Redox biology · 2024Article
- Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice.Scientific reports · 2024Article
- A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.Frontiers in pharmacology · 2024Review
- Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The anticancer therapy of doxorubicin (Dox) has been limited by its acute and chronic cardiotoxicity. In addition to a causative role of oxidative stress, autophagy appears to play an important role in the regulation of Dox-induced cardiotoxicity. However, the underlying mechanisms remain unclear. Accordingly, we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox-induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic activity. In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were associated with oxidative stress, impaired autophagy, and accumulated polyubiquitinated protein aggregates. However, these Dox-induced adverse effects were exaggerated in Nrf2 knockout (Nrf2(-/-)) mice. In cultured cardiomyocytes, overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox-induced impairment of autophagic flux and accumulation of ubiquitinated protein aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2 exerted opposite effects. Moreover, the exaggerated adverse effects in Dox-intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced activation of autophagy via overexpression of autophagy related gene 5 (Atg5). Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox-induced cardiotoxicity by controlling both oxidative stress and autophagy in the heart.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.