Paroxetine mitigates cardiac remodelling by doxorubicin and increases survival
| Autor: | Marko Vasić, Zorica Nesic, Sofija Glumac, Nina Japundžić-Žigon, Bojana Savić, Marija Kosić, Vladislav Pajović |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Cardiotonic Agents Cardiomyopathy GRK2 RM1-950 030204 cardiovascular system & hematology Pharmacology Muscle hypertrophy GRK3 Contractility 03 medical and health sciences 0302 clinical medicine polycyclic compounds Animals Medicine Doxorubicin Rats Wistar Receptor 030304 developmental biology Cardioprotection 0303 health sciences Cardiotoxicity Antibiotics Antineoplastic Ventricular Remodeling biology business.industry Beta adrenergic receptor kinase General Medicine medicine.disease Rats 3. Good health Paroxetine Gene Expression Regulation biology.protein Therapeutics. Pharmacology Cardiomyopathies business Selective Serotonin Reuptake Inhibitors β-adrenergic receptors medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 145, Iss, Pp 112411-(2022) |
| ISSN: | 0753-3322 |
| Popis: | Doxorubicin (DOX) is an effective anticancer drug. However, its use is hampered by the development of very mortal cardiomyopathy. Here, we investigate whether the co-administration of the antidepressant paroxetine (P), known to exert beneficial cardiovascular effects, would provide effective cardioprotection. Experiments were performed in male Wistar rats randomly assigned to control group (0.5 mL/kg 0.9% NaCl, i.v., n = 7), DOX group (DOX 5 mg /kg i.v., n = 23) and DOX+P group (DOX 5 mg/kg, i.v. plus P 10 mg/kg p.o. daily, beginning five days before DOX administration and during the follow-up period, n = 11). Rats′ body weight and echocardiography parameters were monitored before and after drug/vehicle administration. Cardiac histology was performed post-mortem, as well as beta1-adrenergic receptor (β1-AR), beta2-adrenergic receptor (β2-AR), G protein-coupled receptor kinases type 2 (GRK2), type 3 (GRK3), beta-arrestin 1, and beta-arrestin 2 gene expression using RT-qPCR. DOX-treated rats exhibited bad general condition, adynamia, loss of body weight, and low survival. Echocardiography revealed two phenotypes: cardiomyopathy with left ventricular (LV) hypertrophy (DOX-HCM) and cardiomyopathy with LV dilation (DOX-DCM). In DOX-HCM rats only, there was an increased GRK2 and GRK3 gene expression and synthesis. DOX+P co-treated rats exhibited good general condition, normal spontaneous behaviour, gained weight over time, had increased survival, and preserved LV morphology and contractility. In these rats, gene expression and synthesis of GRK2 and GRK3 were decreased, while β1-AR and β2-AR were increased. Present results show for the first time that P effectively reduces DOX-induced cardiotoxicity and enhances survival. |
| Databáze: | OpenAIRE |
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