Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy

Huang, Chuying; Guo, Yishan; Li, Tuo; Sun, Guogen; Yang, Jinru; Wang, Yuqi; Xiang, Ying; Wang, Li; Jin, Min; Li, Jiao; Zhou, Yong; Han, Bing; Huang, Rui; Qiu, Jiao; Tan, Yong; Hu, Jiaxing; Wei, Yumiao; Wu, Bo; Mao, Yong; Lei, Lingshan; Song, Xiusheng; Li, Shuijie; Wang, Yongsheng; Zhang, Tao

doi:10.1016/j.redox.2023.103024

Cited by 17 publications

(1 citation statement)

References 52 publications

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“…DXZ has been reported to reverse DOX-induced ferroptosis mainly by chelating mitochondrial iron, and its co-administration with Ferrostatin-1 (Fer-1) increased survival in cardiomyopathic rats. Moreover, DOX upregulated GPX4 as well as FTH1 in H9c2 cells (Zhang et al, 2021;Huang et al, 2024). Meanwhile, studies have reported that 2,29-Bipyridine exerts ferroptosis inhibition by chelating intra-mitochondrial iron (Chen et al, 2020).…”

Section: Iron Chelatorsmentioning

confidence: 98%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.

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Section: Iron Chelatorsmentioning

confidence: 98%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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Genetically Engineered Membrane‐Coated Nanoparticles for Enhanced Prostate‐Specific Membrane Antigen Targeting and Ferroptosis Treatment of Castration‐Resistant Prostate Cancer

Li,

Zhang

et al. 2024

Advanced Science

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Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration‐resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e., iron‐dependent program cell death) in CRPC cells. Therefore, inducing ferroptosis in CRPC cells might be an effective therapeutic modality for CRPC. However, nonspecific uptake of ferroptosis inducers can result in undesirable cytotoxicity in major organs. Thus, to precisely induce ferroptosis in CRPC cells, a genetic engineering strategy is proposed to embed a prostate‐specific membrane antigen (PSMA)‐targeting antibody fragment (gy1) in the macrophage membrane, which is then coated onto mesoporous polydopamine (MPDA) nanoparticles to produce a biomimetic nanoplatform. The results indicate that the membrane‐coated nanoparticles (MNPs) exhibit high specificity and affinity toward CRPC cells. On further encapsulation with the ferroptosis inducers RSL3 and iron ions, MPDA/Fe/RSL3@M‐gy1 demonstrates superior synergistic effects in highly targeted ferroptosis therapy eliciting significant therapeutic efficacy against CRPC tumor growth and bone metastasis without increased cytotoxicity. In conclusion, a new therapeutic strategy is reported for the PSMA‐specific, CRPC‐targeting platform for ferroptosis induction with increased efficacy and safety.

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Ferroptosis: Latest evidence and perspectives on plant‐derived natural active compounds mitigating doxorubicin‐induced cardiotoxicity

Wang,

Liu

et al. 2024

J of Applied Toxicology

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Doxorubicin (DOX) is a chemotherapy drug widely used in clinical settings, acting as a first‐line treatment for various malignant tumors. However, its use is greatly limited by the cardiotoxicity it induces, including doxorubicin‐induced cardiomyopathy (DIC). The mechanisms behind DIC are not fully understood, but its potential biological mechanisms are thought to include oxidative stress, inflammation, energy metabolism disorders, mitochondrial damage, autophagy, apoptosis, and ferroptosis. Recent studies have shown that cardiac injury induced by DOX is closely related to ferroptosis. Due to their high efficacy, availability, and low side effects, natural medicine treatments hold strong clinical potential. Currently, natural medicines have been shown to mitigate DOX‐induced ferroptosis and ease DIC through various functions such as antioxidation, iron ion homeostasis correction, lipid metabolism regulation, and mitochondrial function improvement. Therefore, this review summarizes the mechanisms of ferroptosis in DIC and the regulation by natural plant products, with the expectation of providing a reference for future research and development of inhibitors targeting ferroptosis in DIC.This review explores the mechanisms of ferroptosis in doxorubicin‐induced cardiomyopathy (DIC) and summarizes how natural plant products can alleviate DIC by inhibiting ferroptosis through reducing oxidative stress, correcting iron ion homeostasis, regulating lipid metabolism, and improving mitochondrial function.

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Pharmacological activation of GPX4 ameliorates doxorubicin-induced cardiomyopathy

Cited by 17 publications

References 52 publications

Ferroptosis inhibitors: past, present and future

Ferroptosis inhibitors: past, present and future

Genetically Engineered Membrane‐Coated Nanoparticles for Enhanced Prostate‐Specific Membrane Antigen Targeting and Ferroptosis Treatment of Castration‐Resistant Prostate Cancer

Ferroptosis: Latest evidence and perspectives on plant‐derived natural active compounds mitigating doxorubicin‐induced cardiotoxicity

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