Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model

Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model

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Despite the effectiveness of doxorubicin (DOXO) as a chemotherapeutic agent, dose-dependent development of chronic cardiotoxicity limits its application. The angiotensin-II receptor blocker losartan is commonly used to treat cardiac remodeling of various etiologies. The beta-3 adrenergic receptor ag...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Freiwan Marah
Kovács Mónika Gabriella
Kovács Zsuzsanna
Szűcs Gergő
Dinh Hoa
Losonczi Réka
Siska Andrea
Kriston András
Kovács Ferenc
Horváth Péter
Földesi Imre
Cserni Gábor
Dux László
Csont Tamás Bálint
Sárközy Márta
Dokumentumtípus: Cikk
Megjelent: 2022
Sorozat:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 23 No. 4
Tárgyszavak:
Általános orvostudomány
Klinikai orvostan
doi:10.3390/ijms23042201

mtmt:32689754
Online Access:http://publicatio.bibl.u-szeged.hu/23748
Leíró adatok
Tartalmi kivonat:Despite the effectiveness of doxorubicin (DOXO) as a chemotherapeutic agent, dose-dependent development of chronic cardiotoxicity limits its application. The angiotensin-II receptor blocker losartan is commonly used to treat cardiac remodeling of various etiologies. The beta-3 adrenergic receptor agonist mirabegron was reported to improve chronic heart failure. Here we investigated the effects of losartan, mirabegron and their combination on the development of DOXO-induced chronic cardiotoxicity. Male Wistar rats were divided into five groups: (i) control; (ii) DOXO-only; (iii) losartan-treated DOXO; (iv) mirabegron-treated DOXO; (v) losartan plus mirabegron-treated DOXO groups. The treatments started 5 weeks after DOXO administration. At week 8, echocardiography was performed. At week 9, left ventricles were prepared for histology, qRT-PCR, and Western blot measurements. Losartan improved diastolic but not systolic dysfunction and ameliorated SERCA2a repression in our DOXO-induced cardiotoxicity model. The DOXO-induced overexpression of Il1 and Il6 was markedly decreased by losartan and mirabegron. Mirabegron and the combination treatment improved systolic and diastolic dysfunction and significantly decreased overexpression of Smad2 and Smad3 in our DOXO-induced cardiotoxicity model. Only mirabegron reduced DOXO-induced cardiac fibrosis significantly. Mirabegron and its combination with losartan seem to be promising therapeutic tools against DOXO-induced chronic cardiotoxicity.
Terjedelem/Fizikai jellemzők:Terjedelem: 28 p-Azonosító: 2201
ISSN:1661-6596

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