Effects of Iron Nanoparticles Administration on Ischemia/Reperfusion Injury in Isolated Hearts of Male Wistar Rats

Overview

Journal Physiol Res

Specialty Physiology

Date 2023 Jun 9

PMID 37294119

Authors

L Kindernay

K Ferenczyova

V Farkasova

M Bartekova

I Bernatova

T Ravingerova

Affiliations

Soon will be listed here.

Abstract

Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as "ferroptosis". On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of "survival" kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.

Citing Articles

GDF15 restrains myocardial ischemia-reperfusion injury through inhibiting GPX4 mediated ferroptosis.

Gao Q, Li C, Zhong P, Yu Y, Luo Z, Chen H Aging (Albany NY). 2024; 16(1):617-626.

PMID: 38206295 PMC: 10817394. DOI: 10.18632/aging.205402.

References

Lecour S, Suleman N, Deuchar G, Somers S, Lacerda L, Huisamen B . Pharmacological preconditioning with tumor necrosis factor-alpha activates signal transducer and activator of transcription-3 at reperfusion without involving classic prosurvival kinases (Akt and extracellular signal-regulated kinase). Circulation. 2005; 112(25):3911-8. DOI: 10.1161/CIRCULATIONAHA.105.581058. View

Griecsova L, Farkasova V, Gablovsky I, Khandelwal V, Bernatova I, Tatarkova Z . Effect of maturation on the resistance of rat hearts against ischemia. Study of potential molecular mechanisms. Physiol Res. 2015; 64(Suppl 5):S685-96. DOI: 10.33549/physiolres.933222. View

Bulluck H, Yellon D, Hausenloy D . Reducing myocardial infarct size: challenges and future opportunities. Heart. 2015; 102(5):341-8. PMC: 4789695. DOI: 10.1136/heartjnl-2015-307855. View

Bell R, Mocanu M, Yellon D . Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol. 2011; 50(6):940-50. DOI: 10.1016/j.yjmcc.2011.02.018. View

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

Heusch G . Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res. 2015; 116(4):674-99. DOI: 10.1161/CIRCRESAHA.116.305348. View

Munoz J, Chiong M, Garcia L, Troncoso R, Toro B, Pedrozo Z . Iron induces protection and necrosis in cultured cardiomyocytes: Role of reactive oxygen species and nitric oxide. Free Radic Biol Med. 2009; 48(4):526-34. DOI: 10.1016/j.freeradbiomed.2009.11.017. View

von Haehling S, Ebner N, Evertz R, Ponikowski P, Anker S . Iron Deficiency in Heart Failure: An Overview. JACC Heart Fail. 2018; 7(1):36-46. DOI: 10.1016/j.jchf.2018.07.015. View

Hirst J . Mitochondrial complex I. Annu Rev Biochem. 2013; 82:551-75. DOI: 10.1146/annurev-biochem-070511-103700. View

10.

Forcina G, Dixon S . GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis. Proteomics. 2019; 19(18):e1800311. DOI: 10.1002/pmic.201800311. View

11.

Kindernay L, Farkasova V, Neckar J, Hrdlicka J, Ytrehus K, Ravingerova T . Impact of Maturation on Myocardial Response to Ischemia and the Effectiveness of Remote Preconditioning in Male Rats. Int J Mol Sci. 2021; 22(20). PMC: 8540346. DOI: 10.3390/ijms222011009. View

12.

Cave A . Preconditioning induced protection against post-ischaemic contractile dysfunction: characteristics and mechanisms. J Mol Cell Cardiol. 1995; 27(4):969-79. DOI: 10.1016/0022-2828(95)90066-7. View

13.

Laubertova L, Dvorakova M, Balis P, Puzserova A, Zitnanova I, Bernatova I . Preliminary Findings on the Effect of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles and Acute Stress on Selected Markers of Oxidative Stress in Normotensive and Hypertensive Rats. Antioxidants (Basel). 2022; 11(4). PMC: 9030389. DOI: 10.3390/antiox11040751. View

14.

Lesnefsky E, Chen Q, Tandler B, Hoppel C . Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies. Annu Rev Pharmacol Toxicol. 2016; 57:535-565. PMC: 11060135. DOI: 10.1146/annurev-pharmtox-010715-103335. View

15.

Chan S, Lian Q, Chen M, Jiang D, Ho J, Cheung Y . Deferiprone inhibits iron overload-induced tissue factor bearing endothelial microparticle generation by inhibition oxidative stress induced mitochondrial injury, and apoptosis. Toxicol Appl Pharmacol. 2017; 338:148-158. DOI: 10.1016/j.taap.2017.11.005. View

16.

Walker M, Curtis M, Hearse D, CAMPBELL R, Janse M, Yellon D . The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion. Cardiovasc Res. 1988; 22(7):447-55. DOI: 10.1093/cvr/22.7.447. View

17.

Hausenloy D, Yellon D . Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection. Heart Fail Rev. 2007; 12(3-4):217-34. DOI: 10.1007/s10741-007-9026-1. View

18.

Chevion M, Jiang Y, Berenshtein E, Uretzky G, Kitrossky N . Copper and iron are mobilized following myocardial ischemia: possible predictive criteria for tissue injury. Proc Natl Acad Sci U S A. 1993; 90(3):1102-6. PMC: 45819. DOI: 10.1073/pnas.90.3.1102. View

19.

Berenshtein E, Vaisman B, Kitrossky N, Konijn A, Chevion M . Roles of ferritin and iron in ischemic preconditioning of the heart. Mol Cell Biochem. 2002; 234-235(1-2):283-92. View

20.

Gonzalez-Gomez M, Belderbos S, Yanez-Vilar S, Pineiro Y, Cleeren F, Bormans G . Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging. Nanomaterials (Basel). 2019; 9(11). PMC: 6915788. DOI: 10.3390/nano9111626. View