In:
Naunyn-Schmiedeberg's Archives of Pharmacology, Springer Science and Business Media LLC, Vol. 395, No. 12 ( 2022-12), p. 1537-1548
Kurzfassung:
The current study aimed to investigate the cardiotoxic effect of dexamethasone-high-dose in rats, the therapeutic effect of carvedilol and the role of α1-adrenergic receptor (α1AR). The experiment involved 6 groups: control, dexamethasone (10 mg/kg), carvedilol (10 mg/kg), phenylephrine (1 mg/kg), phenylephrine plus carvedilol and propranolol (30 mg/kg). Drugs and vehicles were given for 7 days. Dexamethasone was given with the drugs in the last 4 groups. On the 8 th -day and after overnight fasting, serum and cardiac samples were collected. Serum levels of cardiac troponin I and creatine kinase–myoglobin as well as cardiac levels of diacylglycerol, malondialdehyde, kinase activity of Akt, transforming growth factor-β, Smad3 and alpha smooth muscle actin were measured. Cardiac samples were also used for histopathological examination using hematoxylin–eosin and Sirius red stains, in addition to immunohistochemical examination using β-arrestin2 antibody. Dexamethasone induced cardiac injury via increasing oxidative stress, apoptosis and profibrotic signals. Carvedilol significantly reduced the dexamethasone-induced cardiotoxicity. Using phenylephrine, a competitive α1-agonist, with carvedilol potentiated the cardioprotective actions of carvedilol. Propranolol, a β-blocker without activity on α1ARs, showed higher cardiac protection than carvedilol. Dexamethasone-high-dose upregulates cardiac oxidative stress, apoptotic and profibrotic signals and induces cardiac injury. Blocking the α1-adrenergic receptor by carvedilol attenuates its cardioprotective effects against dexamethasone-induced cardiotoxicity.
Materialart:
Online-Ressource
ISSN:
0028-1298
,
1432-1912
DOI:
10.1007/s00210-022-02285-5
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2022
ZDB Id:
1462940-9
SSG:
15,3
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