Targeting Ferroptosis in Ischemia/reperfusion Renal Injury

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2022 Aug 3

PMID 35920897

Authors

Komal Thapa

Thakur Gurjeet Singh

Amarjot Kaur

Affiliations

Soon will be listed here.

Abstract

Renal I/R injury is a severe medical condition contributing to acute kidney injury (AKI), leading to rapid kidney dysfunction and high mortality rates. It is generally observed during renal transplantation, shock, trauma, and urologic and cardiovascular surgery, for which there is no effective treatment. Cell death and damage are commonly linked to I/R. Cell death triggered by iron-dependent lipid peroxidation, such as ferroptosis, has been demonstrated to have a significant detrimental effect in renal IRI models, making it a new type of cell death currently being researched. Ferroptosis is a nonapoptotic type of cell death that occurs when free iron enters the cell and is a critical component of many biological processes. In ferroptosis-induced renal I/R injury, iron chelators such as Deferasirox, Deferiprone, and lipophilic antioxidants are currently suppressed lipid peroxidation Liproxstatin-1 (Lip-1), Ferrostatin-1 along with antioxidants like vitamin and quercetin. Ferroptosis has been considered a potential target for pharmaceutical intervention to alleviate renal IRI-associated cell damage. Thus, this review emphasized the role of ferroptosis and its inhibition in renal IRI. Also, Pharmacological modulation of ferroptosis mechanism in renal I/R injury has been conferred. Graphical abstract.

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References

Barayuga S, Pang X, Andres M, Panee J, Bellinger F . Methamphetamine decreases levels of glutathione peroxidases 1 and 4 in SH-SY5Y neuronal cells: protective effects of selenium. Neurotoxicology. 2013; 37:240-6. PMC: 3717519. DOI: 10.1016/j.neuro.2013.05.009. View

Bersuker K, Hendricks J, Li Z, Magtanong L, Ford B, Tang P . The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019; 575(7784):688-692. PMC: 6883167. DOI: 10.1038/s41586-019-1705-2. View

Bertrand R . Iron accumulation, glutathione depletion, and lipid peroxidation must occur simultaneously during ferroptosis and are mutually amplifying events. Med Hypotheses. 2017; 101:69-74. DOI: 10.1016/j.mehy.2017.02.017. View

Cardoso B, Hare D, Bush A, Roberts B . Glutathione peroxidase 4: a new player in neurodegeneration?. Mol Psychiatry. 2016; 22(3):328-335. DOI: 10.1038/mp.2016.196. View

Casanas-Sanchez V, Perez J, Fabelo N, Quinto-Alemany D, Diaz M . Docosahexaenoic (DHA) modulates phospholipid-hydroperoxide glutathione peroxidase (Gpx4) gene expression to ensure self-protection from oxidative damage in hippocampal cells. Front Physiol. 2015; 6:203. PMC: 4510835. DOI: 10.3389/fphys.2015.00203. View

Choi N, Whitlock R, Klassen J, Zappitelli M, Arora R, Rigatto C . Early intraoperative iron-binding proteins are associated with acute kidney injury after cardiac surgery. J Thorac Cardiovasc Surg. 2018; 157(1):287-297.e2. DOI: 10.1016/j.jtcvs.2018.06.091. View

Conrad M, Sato H . The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond. Amino Acids. 2011; 42(1):231-46. DOI: 10.1007/s00726-011-0867-5. View

Diallo I, Ho J, Laffont B, Laugier J, Benmoussa A, Lambert M . Altered microRNA Transcriptome in Cultured Human Liver Cells upon Infection with Ebola Virus. Int J Mol Sci. 2021; 22(7). PMC: 8038836. DOI: 10.3390/ijms22073792. View

Doll S, Proneth B, Tyurina Y, Panzilius E, Kobayashi S, Ingold I . ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2016; 13(1):91-98. PMC: 5610546. DOI: 10.1038/nchembio.2239. View

10.

Doll S, Porto Freitas F, Shah R, Aldrovandi M, Costa Da Silva M, Ingold I . FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019; 575(7784):693-698. DOI: 10.1038/s41586-019-1707-0. View

11.

Fang X, Cai Z, Wang H, Han D, Cheng Q, Zhang P . Loss of Cardiac Ferritin H Facilitates Cardiomyopathy via Slc7a11-Mediated Ferroptosis. Circ Res. 2020; 127(4):486-501. DOI: 10.1161/CIRCRESAHA.120.316509. View

12.

Finazzi D, Arosio P . Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration. Arch Toxicol. 2014; 88(10):1787-802. DOI: 10.1007/s00204-014-1329-0. View

13.

Frei B, Kim M, Ames B . Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc Natl Acad Sci U S A. 1990; 87(12):4879-83. PMC: 54222. DOI: 10.1073/pnas.87.12.4879. View

14.

Friedmann Angeli J, Schneider M, Proneth B, Tyurina Y, Tyurin V, Hammond V . Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014; 16(12):1180-91. PMC: 4894846. DOI: 10.1038/ncb3064. View

15.

Fujii J, Homma T, Kobayashi S . Ferroptosis caused by cysteine insufficiency and oxidative insult. Free Radic Res. 2019; 54(11-12):969-980. DOI: 10.1080/10715762.2019.1666983. View

16.

Gryzik M, Asperti M, Denardo A, Arosio P, Poli M . NCOA4-mediated ferritinophagy promotes ferroptosis induced by erastin, but not by RSL3 in HeLa cells. Biochim Biophys Acta Mol Cell Res. 2020; 1868(2):118913. DOI: 10.1016/j.bbamcr.2020.118913. View

17.

Gupta A, Khan H, Kaur A, Singh T . Novel Targets Explored in the Treatment of Alcohol Withdrawal Syndrome. CNS Neurol Disord Drug Targets. 2020; 20(2):158-173. DOI: 10.2174/1871527319999201118155721. View

18.

Haase M, Bellomo R, Haase-Fielitz A . Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury. J Am Coll Cardiol. 2010; 55(19):2024-33. DOI: 10.1016/j.jacc.2009.12.046. View

19.

Han C, Liu Y, Dai R, Ismail N, Su W, Li B . Ferroptosis and Its Potential Role in Human Diseases. Front Pharmacol. 2020; 11:239. PMC: 7090218. DOI: 10.3389/fphar.2020.00239. View

20.

Hatcher H, Singh R, Torti F, Torti S . Synthetic and natural iron chelators: therapeutic potential and clinical use. Future Med Chem. 2011; 1(9):1643-70. PMC: 3821171. DOI: 10.4155/fmc.09.121. View