Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury
Abstract
:1. Introduction
2. Pathological Mechanism of Ferroptosis in I/R Injury
3. Therapeutic Strategies Targeting Ferroptosis in I/R Injury
3.1. Ferroptosis in Cerebral I/R Injury
3.1.1. Therapeutic Targets of Ferroptosis in Cerebral I/R Injury
3.1.2. Pharmacological Therapies Targeting Ferroptosis in Cerebral I/R Injury
3.2. Ferroptosis in Myocardial I/R Injury
3.2.1. Therapeutic Targets of Ferroptosis in Myocardial I/R Injury
3.2.2. Pharmacological Therapies Targeting Ferroptosis in Myocardial I/R Injury
3.3. Ferroptosis in Lung I/R Injury
3.4. Ferroptosis in Hepatic I/R Injury
3.4.1. Therapeutic Targets of Ferroptosis in Hepatic I/R Injury
3.4.2. Pharmacological Therapies Targeting Ferroptosis in Hepatic I/R Injury
3.5. Ferroptosis in Renal I/R Injury
3.5.1. Therapeutic Targets of Ferroptosis in Renal I/R Injury
3.5.2. Pharmacological Therapies Targeting Ferroptosis in Renal I/R Injury
3.6. Ferroptosis in Intestinal I/R Injury
4. Conclusions and Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Therapeutic Targets | Diseases | Model | Key Mechanism | References |
---|---|---|---|---|
Tau | Cerebral IRI | In vivo | Tau-iron interaction, inhibit iron overload | [12] |
Ferritin | Cerebral IRI | In vivo/In vitro | Regulate p53 and SLC7A11 | [13,14] |
Mitochondrial ferritin | Cerebral IRI | In vivo | Inhibit iron overload, inhibit lipid peroxidation | [15] |
NCOA4 and USP14 | Cerebral IRI | In vivo/In vitro | Promote ferritinophagy | [14] |
UBIAD1 | Cerebral IRI | In vivo/In vitro | Inhibit lipid peroxidation | [16] |
PGE2 | Cerebral IRI | In vivo/Human samples | Inhibit iron accumulation and lipid peroxidation | [17] |
SAT1 | Cerebral IRI | In vivo/In vitro | Transcriptional target of p53, induce lipid peroxidation | [18] |
Thrombin | Cerebral IRI | In vivo/In vitro | Instigate esterification of ACSL4 | [19] |
LncRNA PVT1/miR-214 | Cerebral IRI | In vivo/In vitro | Inhibit TfR1 and p53 | [20] |
Transferrin and glutamine | Myocardial IRI | In vivo/In vitro | Ferroptosis inducer | [21] |
USP22 | Myocardial IRI | In vivo/In vitro | Regulate SIRT1/p53/SLC7A11 axis | [22] |
USP7 | Myocardial IRI | In vivo/In vitro | Upregulate p53/TfR1 pathway | [23] |
FPN | Myocardial IRI | In vivo/In vitro | Regulate iron homeostasis | [24] |
DNMT-1 | Myocardial IRI | In vivo/In vitro | Promote NCOA4-mediated ferritinophagy | [25] |
OxPCs | Myocardial IRI | In vivo/In vitro | Suppress GPX4 activity | [26] |
ELAVL1 | Myocardial IRI | In vivo/In vitro | Promote autophagic ferroptosis | [27] |
MiR-135b-3p | Myocardial IRI | In vivo/In vitro | Downregulate GPX4 expression | [28] |
LncAABR07025387.1 | Myocardial IRI | In vivo/In vitro | Sponge miR-205 to enhance ACSL4 expression | [29] |
LncRNA Mir9-3hg | Myocardial IRI | In vivo/In vitro | Regulate Pum2/PRDX6 axis | [30] |
MET | Liver IRI | In vivo/In vitro | Disrupt iron metabolism | [31] |
HUWE1 | Liver IRI | In vivo/In vitro/Human samples | Target TfR1 for proteasomal degradation | [32] |
MiR-29a-3p | Liver IRI | In vivo/In vitro | Downregulate IREB2 expression | [33] |
ALR | Renal IRI | In vitro | Anti-oxidant, upregulate GPX4 expression | [34] |
Panx1 | Renal IRI | In vivo/In vitro | Regulate HO-1, NCOA4 and FTH1 | [35] |
CIRBP | Renal IRI | In vivo/In vitro | Regulate ELAVL1 to promote ferritinophagy | [36] |
Legumain | Renal IRI | In vivo/In vitro | Promote degradation of GPX4 | [37] |
IDO | Renal IRI | In vitro | Induce AhR-mediated ferroptosis | [38] |
LSD1 | Renal IRI | In vivo/In vitro | Upregulate TLR4/NOX4 pathway | [39] |
MiR-182-5p and miR-378-3p | Renal IRI | In vivo/In vitro | Downregulate GPX4 and SLC7A11 expression | [40] |
MiR-3587 | Renal IRI | In vitro | Downregulate HO-1 expression | [41] |
Sp1 | Intestinal IRI | In vivo/In vitro/Human samples | Increase ACSL4 transcription | [42] |
TRPV1 | Intestinal IRI | In vivo/In vitro/Human samples | Upregulate GPX4 expression | [43] |
Nrf2 | IIR-induced lung injury | In vivo/In vitro | Upregulate SLC7A11-related axis | [44,45,46] |
p53 | IIR-induced lung injury | In vivo/In vitro | Regulate Nrf2 signaling pathway | [47] |
Reagents | Diseases | Model | Function | References |
---|---|---|---|---|
Selenium compounds | Cerebral IRI | In vivo/In vitro | Drive GPX4 expression | [48,49,50] |
Carvacrol | Cerebral IRI | In vitro | Upregulate GPX4 expression | [51] |
Rehmannioside A | Cerebral IRI | In vivo/In vitro/Human samples | Activate SLC7A11/GPX4 axis | [52] |
Galangin | Cerebral IRI | In vivo/In vitro | Activate SLC7A11/GPX4 axis | [53] |
Carthamin yellow | Cerebral IRI | In vivo | Inhibit ACSL4 expression | [54] |
Kaempferol | Cerebral IRI | In vitro | Activate Nrf2/SLC7A11/GPX4 axis | [55] |
Liproxstatin-1 | Cerebral, myocardial, lung, liver, intestinal IRI | In vivo/In vitro/Human samples | Inhibit lipid peroxidation | [12,42,56,57,58] |
Ferrostatin-1 | Cerebral, myocardial, lung, liver, renal IRI | In vivo/In vitro/Human samples | Inhibit lipid peroxidation | [12,20,26,31,59,60,61,62] |
Deferoxamine | Myocardial, liver, renal IRI | In vivo/In vitro | Iron chelator | [21,31,61,62,63] |
Dexrazoxane | Myocardial IRI | In vivo/In vitro | Iron chelator | [64] |
Gossypol acetic acid | Myocardial IRI | In vivo/In vitro | Anti-oxidant/iron-chelating | [65] |
Histochrome | Myocardial IRI | In vivo/In vitro | Anti-oxidant/iron-chelating | [66] |
Cyanidin-3-glucoside | Myocardial IRI | In vivo/In vitro | Anti-oxidant | [67] |
Xanthohumol | Myocardial IRI | In vivo/In vitro | Anti-oxidant/upregulate GPX4 expression | [68] |
Etomidate | Myocardial IRI | In vivo | Upregulate Nrf2/HO-1 pathway | [69] |
Naringenin | Myocardial IRI | In vivo/In vitro | Upregulate Nrf2/SLC7A11/GPX4 axis | [70] |
Britanin | Myocardial IRI | In vivo/In vitro | Upregulate Nrf2/GPX4 axis | [71] |
Propofol | Myocardial IRI | In vivo/In vitro | Regulate AKT/p53 pathway | [72] |
Ferulic acid | Myocardial IRI | In vivo | Upregulate AMPKα2 expression | [73] |
PDA NPs | Myocardial IRI | In vivo/In vitro | Inhibit iron deposition and lipid peroxidation | [74] |
UAMC-3203 | Myocardial IRI | In vivo | Inhibit lipid peroxidation | [75] |
Resveratrol | Myocardial IRI | In vivo/In vitro | Regulate USP19-Beclin 1 autophagy/upregulate GPX4 | [76] |
Dexmedetomidine | Myocardial IRI | In vivo | Upregulate SLC7A11/GPX4 axis | [77] |
Irisin | Lung, renal IRI | In vivo/In vitro | Upregulate Nrf2/HO-1 axis/upregulate GPX4 | [60,78] |
Rosiglitazone | Lung, intestinal IRI | In vivo/In vitro | Inhibit ACSL4 expression | [42,57] |
α-tocopherol | Liver IRI | In vivo | Inhibit lipid peroxidation | [61] |
Pachymic acid | Renal IRI | In vivo | Upregulate Nrf2 signaling pathway | [79] |
16–86 | Renal IRI | In vivo/In vitro | Inhibit lipid peroxidation | [80] |
XJB-5-131 | Renal IRI | In vivo | Inhibit lipid peroxidation/anti-oxidant | [81] |
Quercetin | Renal IRI | In vivo/In vitro | Inhibit ATF3/SLC7A11/GPX4 axis | [82] |
Nec-1f | Renal IRI | In vivo/In vitro | Inhibit RIPK1 kinase activity and ferroptosis | [83] |
Entacapone | Renal IRI | In vivo/In vitro | Upregulate SLC7A11 repression | [84] |
APG | Intestinal IRI | In vivo/In vitro | Inhibit MAO-B/anti-oxidant | [85] |
Capsiate | Intestinal IRI | In vivo/In vitro | Enhance GPX4 expression/activate TRPV1 | [43] |
iASPP | IIR-induced lung injury | In vivo/In vitro | Upregulate Nrf2 signaling/p53 inhibitor | [47] |
Isoliquiritin apioside | IIR-induced lung injury | In vivo/In vitro | Downregulate Hif-1α expression | [86] |
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Pan, Y.; Wang, X.; Liu, X.; Shen, L.; Chen, Q.; Shu, Q. Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury. Antioxidants 2022, 11, 2196. https://doi.org/10.3390/antiox11112196
Pan Y, Wang X, Liu X, Shen L, Chen Q, Shu Q. Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury. Antioxidants. 2022; 11(11):2196. https://doi.org/10.3390/antiox11112196
Chicago/Turabian StylePan, Yihang, Xueke Wang, Xiwang Liu, Lihua Shen, Qixing Chen, and Qiang Shu. 2022. "Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury" Antioxidants 11, no. 11: 2196. https://doi.org/10.3390/antiox11112196