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Combined diosmin and bisoprolol attenuate cobalt chloride-induced cardiotoxicity and endothelial dysfunction through modulating miR-143-3P/MAPK/MCP-1, ERK5/CXCR4, Orai-1/STIM-1 signaling pathways.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2024 Oct 25; Vol. 140, pp. 112777. Date of Electronic Publication: 2024 Aug 02. - Publication Year :
- 2024
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Abstract
- Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2, 150 mg/kg/day, p.o.), bisoprolol (25 mg/kg/day, p.o.); diosmin (100 mg/kg/day, p.o.) and bisoprolol + diosmin + Cocl2 groups. At the end of the experimental period, serum was taken for estimation of cardiac function, lipid profile, and pro/anti-inflammatory cytokines. Moreover, tissue samples were collected for evaluation of oxidative stress, endothelial dysfunction, α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Diosmin and bisoprolol, either alone or in combination, enhance heart function by reducing abnormalities in the electrocardiogram and the hypotension brought on by CoCl2. Additionally, they significantly ameliorate endothelial dysfunction by downregulating the cardiac expressions of α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Bisoprolol and diosmin produced modulatory activity against inflammatory state, redox balance, and atherogenic index concurrently. Together, diosmin and bisoprolol, either alone or in combination, significantly reduced all the cardiac alterations brought on by CoCl2. The capacity to obstruct hypoxia-induced α-SMA, PKC-α, MiR-143-3P/MAPK/MCP-1, MiR-143-3P/ERK5/CXCR4, Orai-1/STIM-1 signaling activation, as well as their anti-inflammatory, antioxidant, and anti-apoptotic properties, may be responsible for these cardio-protective results.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Male
Rats
Rats, Wistar
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Apoptosis drug effects
Oxidative Stress drug effects
Chemokine CCL2
Cobalt toxicity
Receptors, CXCR4 metabolism
Receptors, CXCR4 genetics
Cardiotoxicity drug therapy
Bisoprolol pharmacology
Bisoprolol therapeutic use
Signal Transduction drug effects
MicroRNAs metabolism
MicroRNAs genetics
Diosmin pharmacology
Diosmin therapeutic use
ORAI1 Protein metabolism
ORAI1 Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 140
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39088923
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112777