Effects of H 2 S-donor ascorbic acid derivative and ischemia/reperfusion-induced injury in isolated rat hearts.

Autor: Tánczos B; Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; HUN-REN-DE Pharmamodul Research Group, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary., Vass V; Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; HUN-REN-DE Pharmamodul Research Group, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary; Doctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98., Hungary., Szabó E; Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; HUN-REN-DE Pharmamodul Research Group, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary., Lovas M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary., Kattoub RG; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; Doctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98., Hungary., Bereczki I; HUN-REN-DE Pharmamodul Research Group, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary., Borbás A; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary., Herczegh P; HUN-REN-DE Pharmamodul Research Group, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary., Tósaki Á; Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary; HUN-REN-DE Pharmamodul Research Group, University of Debrecen, 4032 Debrecen, Nagyerdei krt. 98, Hungary. Electronic address: tosaki.arpad@pharm.unideb.hu.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2024 Apr 01; Vol. 195, pp. 106721. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1016/j.ejps.2024.106721
Abstrakt: Hydrogen sulfide (H 2 S), a gasotransmitter, plays a crucial role in vasorelaxation, anti-inflammatory processes and mitigating myocardial ischemia/reperfusion-induced injury by regulating various signaling processes. We designed a water soluble H 2 S-releasing ascorbic acid derivative, BM-164, to combine the beneficial cardiovascular and anti-inflammatory effects of H 2 S with the excellent water solubility and antioxidant properties of ascorbic acid. DPPH antioxidant assay revealed that the antioxidant activity of BM-164 in the presence of a myocardial tissue homogenate (extract) increased continuously over the 120 min test interval due to the continuous release of H 2 S from BM-164. The cytotoxicity of BM-164 was tested by MTT assay on H9c2 cells, which resulted in no cytotoxic effect at concentrations of 10 to 30 μM. The possible beneficial effects of BM-164 (30 µM) was examined in isolated 'Langendorff' rat hearts. The incidence of ventricular fibrillation (VF) was significantly reduced from its control value of 79 % to 31 % in the BM-164 treated group, and the infarct size was also diminished from the control value of 28 % to 14 % in the BM-164 treated group. However, coronary flow (CF) and heart rate (HR) values in the BM-164 treated group did not show significantly different levels in comparison with the drug-free control, although a non-significant recovery in both CF and HR was observed at each time point. We attempted to reveal the mechanism of action of BM-164, focusing on the processes of autophagy and apoptosis. The expression of key autophagic and apoptotic markers in isolated rat hearts were detected by Western blot analysis. All the examined autophagy-related proteins showed increased expression levels in the BM-164 treated group in comparison to the drug-free control and/or ascorbic acid treated groups, while the changes in the expression of apoptotic markers were not obvious. In conclusion, the designed water soluble H 2 S releasing ascorbic acid derivative, BM-164, showed better cardiac protection against ischemia/reperfusion-induced injury compared to the untreated and ascorbic acid treated hearts, respectively.
Competing Interests: Declaration of competing interest All authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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