Intermittent Hypoxic Preconditioning Plays a Cardioprotective Role in Doxorubicin-Induced Cardiomyopathy.

Autor: Galis P; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia., Bartosova L; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia., Farkasova V; Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04, Bratislava, Slovakia., Szobi A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia., Horvath C; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia., Kovacova D; Faculty of Medicine, Institute of Pathophysiology, Comenius University, Špitálska 24, 813 72, Bratislava, Slovakia., Adameova A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia.; Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04, Bratislava, Slovakia., Rajtik T; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32, Bratislava, Slovakia. rajtik@fpharm.uniba.sk.; Institute for Heart Research, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04, Bratislava, Slovakia. rajtik@fpharm.uniba.sk.
Jazyk: angličtina
Zdroj: Cardiovascular toxicology [Cardiovasc Toxicol] 2023 Jun; Vol. 23 (5-6), pp. 185-197. Date of Electronic Publication: 2023 Apr 29.
DOI: 10.1007/s12012-023-09793-7
Abstrakt: Intermittent hypoxic preconditioning (IHP) is a well-established cardioprotective intervention in models of ischemia/reperfusion injury. Nevertheless, the significance of IHP in different cardiac pathologies remains elusive. In order to investigate the role of IHP and its effects on calcium-dependent signalization in HF, we employed a model of cardiomyopathy induced by doxorubicin (Dox), a widely used drug from the class of cardiotoxic antineoplastics, which was i.p. injected to Wistar rats (4 applications of 4 mg/kg/week). IHP-treated group was exposed to IHP for 2 weeks prior to Dox administration. IHP ameliorated Dox-induced reduction in cardiac output. Western blot analysis revealed increased expression of sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2a) while the expression of hypoxia inducible factor (HIF)-1-α, which is a crucial regulator of hypoxia-inducible genes, was not changed. Animals administered with Dox had further decreased expression of TRPV1 and TRPV4 (transient receptor potential, vanilloid subtype) ion channels along with suppressed Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activation. In summary, IHP-mediated improvement in cardiac output in the model of Dox-induced cardiomyopathy is likely a result of increased SERCA2a expression which could implicate IHP as a potential protective intervention in Dox cardiomyopathy, however, further analysis of observed effects is still required.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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