Ferroptosis and myocardial ischemia-reperfusion: mechanistic insights and new therapeutic perspectives

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 1, 2024

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following myocardial infarction. Ferroptosis, type regulated cell death driven by iron and marked lipid peroxidation, has garnered growing interest for its crucial involvement pathogenesis MIRI.This review comprehensively examines mechanisms ferroptosis, focusing on regulation through metabolism, VDAC signaling, antioxidant system dysregulation. We also compare ferroptosis with other forms to highlight distinct characteristics. Furthermore, MIRI examined focus recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit mitigate are reviewed, providing new insights into potential clinical applications.

Language: Английский

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Tanshinone IIA Ameliorates Myocardial Ischemia–Reperfusion Injury via Activating HDAC1‐Repressed Nrf2‐xCT/Gpx4/HO‐1 Axis

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(4)

Published: April 1, 2025

Myocardial ischemia/reperfusion injury (MIRI) brings secondary to heart tissues and involves complicated pathophysiological activities, such as cell death, oxidative stress, inflammation. HDAC1 (Histone Deacetylase 1) has been documented strengthen MIRI; our study intended investigate the concrete regulatory mechanisms functions of tanshinone IIA on in MIRI, which might provide experimental proofs for adjuvant application treatment MIRI. Genecards SwissTargetPrediction websites were utilized download myocardial infarction-related IIA-targeted genes respectively, then String website was applied display protein-protein interaction (PPI) network. The Cytoscape software subsequently used select PPI network hub genes. AutoDockTools PyMOL operate molecular docking visualize results between HDAC1, Oxygen-glucose deprivation/reoxygenation (OGD/R)-treated myocardiocytes model protein levels nuclear factor erythroid 2-related 2 (Nrf2)-regulated pathway examined by western blot, viability apoptosis evaluated CCK8, Tunnel, flow cytometry assays. lactate dehydrogenase, creatine kinase-MB, malondialdehyde, reduced glutathione, Fe2+ assessed corresponding kit, MIRI rat models constructed verify therapeutic effects vivo. Finally, hematoxylin eosin staining immunohistochemistry pathological changes 4-hydroxynonenal respectively. possible target involved infarction process. Tanshinone could bind amino acid residues with high affinity. Besides, elevated OGD/R-treated myocardiocytes, pretreatment ameliorated myocardiocyte apoptosis, release inflammatory mediators, ferroptosis under following OGD/R treatment, abolished upregulation. suppressed expression further activated Nrf2-xCT/Gpx4/HO-1 axis operation. Functionally, pre-injection infarcted areas via activating HDAC1-suppressed attenuate response, HDAC1-repressed axis, promoted salvage

Language: Английский

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Traditional Chinese Medicine for Inhibiting Ferroptosis in Ischemic‐Related Diseases

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2025, Volume and Issue: 136(6)

Published: April 28, 2025

ABSTRACT Ischemic‐related diseases, such as myocardial infarction and stroke, are primarily driven by a deficit in oxygen supply leading to cellular damage death. Ferroptosis has emerged an important mechanism contributing the progression of ischemic injury, characterized iron‐dependent lipid peroxidation. This review aims provide comprehensive overview significant mechanisms underlying ferroptosis conditions explores potential effects traditional Chinese medicines (TCMs) their extracts. Numerous compounds extracted from TCMs, including flavonoids, polyphenols terpenes, exhibit potent antiferroptotic activating nuclear factor erythroid 2–related 2, upregulating glutathione peroxidase 4, inhibiting peroxidation so on. These properties render TCMs promising candidate for developing novel therapeutic strategies. underscores importance investigating interactions between within context diseases. findings valuable insights future research identify targets associated with regulation, thereby expanding pharmacological perspective treating diseases revealing Additionally, this highlights relevance integrating modern medical approaches addressing complex health issues.

Language: Английский

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Preconditioning with Ginsenoside Rg3 mitigates cardiac injury induced by high-altitude hypobaric hypoxia exposure in mice by suppressing ferroptosis through inhibition of the RhoA/ROCK signaling pathway

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 337, P. 118861 - 118861

Published: Sept. 24, 2024

Language: Английский

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