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

Lin, Jianhong; Yang, Kun‐Ta; Ting, Pei-Ching; Luo, Yu-Po; Lin, Ding-Jyun; Wang, Yi-Shun; Chang, Jui-Chih

doi:10.3390/biom11111667

Cited by 33 publications

(18 citation statements)

References 33 publications

(49 reference statements)

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“…Additionally, the iron-chelating effect of GAA has been confirmed [ 150 ]. It was recently reported that GAA was beneficial in myocardial I/R by protecting cardiomyocytes against ferroptosis and reducing infarct size [ 65 ]. Histochrome (HC) is a water-soluble form of echinochrome A with strong iron-chelating and antioxidant properties [ 151 ].…”

Section: Therapeutic Strategies Targeting Ferroptosis In I/r Injurymentioning

confidence: 99%

Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury

et al. 2022

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Ischemia-reperfusion (I/R) injury is a major challenge in perioperative medicine that contributes to pathological damage in various conditions, including ischemic stroke, myocardial infarction, acute lung injury, liver transplantation, acute kidney injury and hemorrhagic shock. I/R damage is often irreversible, and current treatments for I/R injury are limited. Ferroptosis, a type of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides, has been implicated in multiple diseases, including I/R injury. Emerging evidence suggests that ferroptosis can serve as a therapeutic target to alleviate I/R injury, and pharmacological strategies targeting ferroptosis have been developed in I/R models. Here, we systematically summarize recent advances in research on ferroptosis in I/R injury and provide a comprehensive analysis of ferroptosis-regulated genes investigated in the context of I/R, as well as the therapeutic applications of ferroptosis regulators, to provide insights into developing therapeutic strategies for this devastating disease.

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Section: Therapeutic Strategies Targeting Ferroptosis In I/r Injurymentioning

confidence: 99%

Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury

et al. 2022

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“…Ferroptosis is a new form of cell necrosis mediated by iron-dependent lipid peroxidation [ 10 ]. Ferroptosis has been related to the mechanism associated with lipopolysaccharide-induced cardiac dysfunction and cardiac ischemia/reperfusion injury [ 11 , 12 ]. Although these changes have been observed in acute injury disease models of the heart, it is not clear whether ferroptosis also involved in myocardial damage in DCM.…”

Section: Introductionmentioning

confidence: 99%

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments and consequently increase risk of mortality. Objective. To characterize the therapeutic effect of 6-gingerol (6-G) on DCM and identify its potential mechanism. Methods. In vivo streptozotocin- (STZ-) induced DM model was established by using a high-fat diet and STZ, followed by low-dose (25 mg/kg) and high-dose (75 mg/kg) 6-G intervention. For an in vitro DCM model, H9c2 rat cardiomyoblast cells were stimulated with high glucose ( glucose = 33 mM) and palmitic acid (100 μM) and then treated with 6-G (100 μM). Histological and echocardiographic analyses were used to assess the effect of 6-G on cardiac structure and function in DCM. Western blotting, ELISA, and real-time qPCR were used to assess the expression of ferroptosis, inflammation, and the Nrf2/HO-1 pathway-related proteins and RNAs. Protein expression of collagen I and collagen III was assessed by immunohistochemistry, and kits were used to assay SOD, MDA, and iron levels. Results. The results showed that 6-G decreased cardiac injury in both mouse and cell models of DCM. The cardiomyocyte hypertrophy and interstitial fibrosis were attenuated by 6-G treatment in vivo and resulted in an improved heart function. 6-G inhibited the expression of ferroptosis-related protein FACL4 and the content of iron and enhanced the expression of anti-ferroptosis-related protein GPX4. In addition, 6-G also diminished the secretion of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. 6-G treatment activated the Nrf2/HO-1 pathway, enhanced antioxidative stress capacity proved by increased activity of SOD, and decreased MDA production. Compared with in vivo, 6-G treatment of H9c2 cells treated with high glucose and palmitic acid could produce a similar effect. Conclusion. These findings suggest that 6-G could protect against DCM by the mechanism of ferroptosis inhibition and inflammation reduction via enhancing the Nrf2/HO-1 pathway.

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“…Icariin (1) ( Liu X. et al, 2021 ), xanthohumol (2) ( Lin et al, 2022 ), britanin (3) ( Lu et al, 2022 ), etomidate (4) ( Lv et al, 2021 ),GAA (5) ( Lin et al, 2021 ),dexmedetomidine (6) ( Wang H. et al, 2022 ), sulforaphane (7) ( Tian Y. et al, 2021 ), naringenin (8) ( Xu et al, 2021 ), C3G (9) ( Shan X. et al, 2021 ), resveratrol (10) ( Xu et al, 2019 ; Li D. et al, 2022 ) , 5-aza-CdR (11) ( Li W. et al, 2021 ), ferulic acid (12) ( Liu XJ. et al, 2021 ), PDA NPs (13) ( Zhang H. et al, 2021 ), atorvastatin (14) ( Peng et al, 2022 ), baicalin (15) ( Fan et al, 2021 ), and ponatinib + deferoxamine (16) ( Tu et al, 2021 ) alleviate ICM through inhibiting ferroptosis ( Table 1 ).…”

Section: Pharmacological Inhibition Of Ferroptosis For Treating Cardi...mentioning

confidence: 99%

Targeting ferroptosis as a promising therapeutic strategy to treat cardiomyopathy

et al. 2023

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Cardiomyopathies are a clinically heterogeneous group of cardiac diseases characterized by heart muscle damage, resulting in myocardium disorders, diminished cardiac function, heart failure, and even sudden cardiac death. The molecular mechanisms underlying the damage to cardiomyocytes remain unclear. Emerging studies have demonstrated that ferroptosis, an iron-dependent non-apoptotic regulated form of cell death characterized by iron dyshomeostasis and lipid peroxidation, contributes to the development of ischemic cardiomyopathy, diabetic cardiomyopathy, doxorubicin-induced cardiomyopathy, and septic cardiomyopathy. Numerous compounds have exerted potential therapeutic effects on cardiomyopathies by inhibiting ferroptosis. In this review, we summarize the core mechanism by which ferroptosis leads to the development of these cardiomyopathies. We emphasize the emerging types of therapeutic compounds that can inhibit ferroptosis and delineate their beneficial effects in treating cardiomyopathies. This review suggests that inhibiting ferroptosis pharmacologically may be a potential therapeutic strategy for cardiomyopathy treatment.

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

Cited by 33 publications

References 33 publications

Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury

Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

Targeting ferroptosis as a promising therapeutic strategy to treat cardiomyopathy

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