Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis

Wang, Zhuoran; Yao, Mengran; Jiang, Leyu; Wang, Lingyan; Yang, Yuqiao; Wang, Quan; Qian, Xi; Zhao, Yu; Qian, Jinqiao

doi:10.1016/j.biopha.2022.113572

Cited by 120 publications

(68 citation statements)

References 32 publications

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“…In 2022, one study discovered that DEX postconditioning could enhance GSH and GPX4 levels in the myocardium, preventing cardiac damage and ferroptosis caused by I/R [ 232 ]. In the same year, Wang et al showed that DEX increased the expression levels of SLC7A11 and GPX4 and protected H9C2 cells from hypoxia/reoxygenation injury through the AMPK/GSK-3β/Nrf2 axis [ 233 ]. Moreover, DEX treatment (0.5 μg/kg/h, pumping injection, before induction of anesthesia to the end of surgery) has been reported to reduce cardiac troponin I and MDA levels and to decrease the incidence of arrhythmias in patients undergoing cardiac valve replacement [ 234 , 235 ].…”

Section: Strategies For Gsh System Activationmentioning

confidence: 99%

Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis

Tan

Yin

et al. 2023

Cell Death Dis

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The glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in the cardiovascular system due to its key contribution to detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption of the GSH system is a critical element in the pathogenesis of myocardial injury. Meanwhile, a newly proposed type of cell death, ferroptosis, has been demonstrated to be closely related to the GSH system, which affects the process and outcome of myocardial injury. Moreover, in facing various pathological challenges, the mammalian heart, which possesses high levels of mitochondria and weak antioxidant capacity, is susceptible to oxidant production and oxidative damage. Therefore, targeted enhancement of the GSH system along with prevention of ferroptosis in the myocardium is a promising therapeutic strategy. In this review, we first systematically describe the physiological functions and anabolism of the GSH system, as well as its effects on cardiac injury. Then, we discuss the relationship between the GSH system and ferroptosis in myocardial injury. Moreover, a comprehensive summary of the activation strategies of the GSH system is presented, where we mainly identify several promising herbal monomers, which may provide valuable guidelines for the exploration of new therapeutic approaches.

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Section: Strategies For Gsh System Activationmentioning

confidence: 99%

Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis

Tan

Yin

et al. 2023

Cell Death Dis

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“…There are also some drugs regulating hypoxia-induced ferroptosis through the mechanisms independent of hypoxia. In myocardial IRI, dexmedetomidine activates Nrf2 via AMPK/GSK-3β (AMP-activated protein kinase/Glycogen synthase kinase 3β) pathway, to inhibit H/R induced-ferroptosis of cardiomyocytes and to protect hearts from IRI [ 160 ]. It was also reported that icariin and irisin protect against myocardial and lung injury, respectively, by suppressing H/R-induced ferroptosis of cardiomyocytes and lung epithelial cells via activating Nrf2/HO-1 signaling [ 161 , 162 ].…”

Section: The Mechanism and Regulation Of Ferroptosis Modulated By Hyp...mentioning

confidence: 99%

Ferroptosis Regulated by Hypoxia in Cells

Zheng

Liang

Zhang

2023

Cells

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Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which is associated with many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, and immunologically distinct from other regulated cell death forms. Ferroptosis is regulated by iron metabolism, lipid metabolism, anti-oxidant defense systems, as well as various signal pathways. Hypoxia, which is found in a group of physiological and pathological conditions, can affect multiple cellular functions by activation of the hypoxia-inducible factor (HIF) signaling and other mechanisms. Emerging evidence demonstrated that hypoxia regulates ferroptosis in certain cell types and conditions. In this review, we summarize the basic mechanisms and regulations of ferroptosis and hypoxia, as well as the regulation of ferroptosis by hypoxia in physiological and pathological conditions, which may contribute to the numerous diseases therapies.

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“…Wang et al demonstrated that myocardial infarction was substantially reduced by dexmedetomidine (Dex), and heart function improved, along with diminished lipid peroxidation and Fe 2+ accumulation. Studies have confirmed that Dex activates NRF2 through the AMPK/GSK-3β pathway to protect the heart from I/R-induced ferroptosis [ 76 ]. Similarly, britanin upregulates GPX4 expression via this pathway, and the knockdown of NRF2 blocks the protective effects of britanin against H/R-induced injury in H9C2 cells [ 77 ].…”

Section: Mechanisms and Targeted Therapies For Ferroptosis In Irimentioning

confidence: 99%

Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury

Zhou

Han

Guo

et al. 2022

Cells

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Ischemia–reperfusion (I/R) is a common pathological phenomenon that occurs in numerous organs and diseases. It generally results from secondary damage caused by the recovery of blood flow and reoxygenation, followed by ischemia of organ tissues, which is often accompanied by severe cellular damage and death. Currently, effective treatments for I/R injury (IRI) are limited. Ferroptosis, a new type of regulated cell death (RCD), is characterized by iron overload and iron-dependent lipid peroxidation. Mounting evidence has indicated a close relationship between ferroptosis and IRI. Ferroptosis plays a significantly detrimental role in the progression of IRI, and targeting ferroptosis may be a promising approach for treatment of IRI. Considering the substantial progress made in the study of ferroptosis in IRI, in this review, we summarize the pathological mechanisms and therapeutic targets of ferroptosis in IRI.

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Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis

Cited by 120 publications

References 32 publications

Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis

Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis

Ferroptosis Regulated by Hypoxia in Cells

Ferroptosis—A New Dawn in the Treatment of Organ Ischemia–Reperfusion Injury

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