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Novel oral edaravone attenuates diastolic dysfunction of diabetic cardiomyopathy by activating the Nrf2 signaling pathway.

Authors :
Wang L
Zeng YQ
Gu JH
Song R
Cang PH
Xu YX
Shao XX
Pu LJ
Luo HY
Zhou XF
Source :
European journal of pharmacology [Eur J Pharmacol] 2022 Apr 05; Vol. 920, pp. 174846. Date of Electronic Publication: 2022 Feb 22.
Publication Year :
2022

Abstract

Oxidative stress plays a crucial role in the pathophysiology of diastolic dysfunction associated with diabetic cardiomyopathy. Novel oral edaravone (OED) alleviates oxidative stress by scavenging free radicals and may be suitable for the treatment of chronic diseases such as diabetic cardiomyopathy. Oral administration of OED to type 2 diabetic rats (induced by high-sugar/high-fat diet and intraperitoneal injection of streptozotocin) for 4 w decreased malondialdehyde and increased superoxide dismutase. Moreover, it significantly improved ratios of early to late diastolic peak velocity, myocardium hypertrophy accompanied by decreased cross-sectional areas of cardiomyocytes, the proportion of apoptotic cells, collagen volume fractions, and deposition of collagen I/III. In H9c2 cells, OED reduced reactive oxygen species, cell surface area, and numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells induced by glucolipotoxicity. OED remarkably upregulated expression of the nuclear factor E2-related factor (Nrf2) signaling pathway both in vivo and in vitro. In addition, OED promoted Nrf2 nuclear translocation and upregulated nicotinamide adenine dinucleotide phosphate quinone oxidoreductase and heme oxygenase. Silencing of Nrf2 abolished the protective effect of OED in H9c2 cells. Our findings demonstrate that OED has the therapeutic potential to ameliorate diastolic dysfunction associated with diabetic cardiomyopathy. Its effect was mainly achieved by attenuating hyperglycemia and hyperlipidemia-induced cardiomyocyte hypertrophy, apoptosis, and fibrosis by activating the Nrf2 signaling pathway.<br /> (Copyright © 2022 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-0712
Volume :
920
Database :
MEDLINE
Journal :
European journal of pharmacology
Publication Type :
Academic Journal
Accession number :
35202676
Full Text :
https://doi.org/10.1016/j.ejphar.2022.174846