Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis

Li, Ting; Tan, Ying; Ouyang, Shan; He, Jin; Liu, Lingling

doi:10.1016/j.gene.2021.145968

Cited by 136 publications

(79 citation statements)

References 42 publications

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“…In recent years, several studies [ 49 – 55 ] found the nephroprotective effects of PD and its aglycone and resveratrol, against cisplatin-induced oxidative stress and inflammation. However, their effects on inhibiting ferroptosis have only recently been reported in myocardial ischemia-reperfusion injury and intracerebral hemorrhage models [ 36 – 38 ]. Our results identified that a 40 mg/kg dose of PD significantly rescued the depletion of GSH and the decrease in GPx4 activity after cisplatin induction, and its effect was almost equivalent to that of a 5 mg/kg dose of Fer-1.…”

Section: Discussionmentioning

confidence: 99%

“…Resveratrol, an aglycone of PD, has been verified to ameliorate myocardial and liver damage caused by iron overload [ 32 – 34 ]; moreover, it has been confirmed that resveratrol can reduce iron load in hemodialysis patients in clinical studies [ 35 ]. Recent studies have noted that PD [ 36 ] or resveratrol [ 37 , 38 ] can inhibit ferroptosis to ameliorate myocardial ischemia-reperfusion injury and brain injury. However, the role of PD in Cis-AKI is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Zhou

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 μM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc− inhibitor erastin (10 μM), and the effect of the 40 μM dose of PD was more obvious than that of ferrostatin-1 (1 μM) and deferoxamine (DFO, 100 μM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc−-GSH-GPx4 axis and iron metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Zhou

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…By contrast, high concentrations of labile iron are highly toxic to cells increasing the risk of cancer, diabetes, neurodegenerative diseases, and cardiovascular diseases [ 5 ]. Importantly, iron overload can also cause a new type of iron-dependent cell death—Ferroptosis [ 6 ]. Thus, iron can act as a double-edged sword, which necessitates accurate regulation of its cellular levels and exquisite equilibrium between iron absorption, circulation, storage, and regulation.…”

Section: Introductionmentioning

confidence: 99%

Iron Metabolism in Aging and Age-Related Diseases

Tian

Yuan

et al. 2022

IJMS

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Iron is a trace metal element necessary to maintain life and is also involved in a variety of biological processes. Aging refers to the natural life process in which the physiological functions of the various systems, organs, and tissues decline, affected by genetic and environmental factors. Therefore, it is imperative to investigate the relationship between iron metabolism and aging-related diseases, including neurodegenerative diseases. During aging, the accumulation of nonheme iron destroys the stability of the intracellular environment. The destruction of iron homeostasis can induce cell damage by producing hydroxyl free radicals, leading to mitochondrial dysfunction, brain aging, and even organismal aging. In this review, we have briefly summarized the role of the metabolic process of iron in the body, then discussed recent developments of iron metabolism in aging and age-related neurodegenerative diseases, and finally, explored some iron chelators as treatment strategies for those disorders. Understanding the roles of iron metabolism in aging and neurodegenerative diseases will fill the knowledge gap in the field. This review could provide new insights into the research on iron metabolism and age-related neurodegenerative diseases.

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“…Many previous results have shown that after OGD/R treatment of primary cultured cardiomyocytes or H9c2 cells, intracellular Fe 2+ , ROS, and MDA have a significant increase. Moreover, the increase in ACSL4 and the decrease in GPX4 have been observed, indicating that OGD/R can trigger cardiac cells ferroptosis [ 27 , 28 , 29 , 30 ]. ROS can cause many different types of cell damage and death.…”

Section: Discussionmentioning

confidence: 99%

“…ROS can cause many different types of cell damage and death. Therefore, the study found that OGD/R induces cell ferroptosis, and different cell deaths can also be observed, such as apoptosis [ 28 , 29 , 30 ] or autophagy [ 27 ]. In our previous study, although GAA significantly inhibits OGD/R-induced cell lipid peroxidation and cell death, the improvement of cell viability cannot achieve the effect of inhibiting lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism

et al. 2021

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Myocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the effects of GAA on myocardial I/R-induced ferroptosis remain unclear. This study investigated the ability of GAA to attenuate I/R-induced ferroptosis in cardiomyocytes along with the underlying mechanisms in a well-established rat model of myocardial I/R and isolated neonatal rat cardiomyocytes. H9c2 cells and cardiomyocytes were treated with the ferroptosis inducers erastin, RSL3, and Fe-SP. GAA could protect H9c2 cells against ferroptotic cell death caused by these ferroptosis inducers by decreasing the production of malondialdehyde and reactive oxygen species, chelating iron content, and downregulating mRNA levels of Ptgs2. GAA could prevent oxygen-glucose deprivation/reperfusion-induced cell death and lipid peroxidation in the cardiomyocytes. Moreover, GAA significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial I/R-induced ferroptotic cell death.

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Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis

Cited by 136 publications

References 42 publications

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Iron Metabolism in Aging and Age-Related Diseases

Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism

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