ISSN 2149-2263 | E-ISSN 2149-2271
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Volume : 25 Issue : 12 Year : 2021
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Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress, inflammation, and Caspase 3 apoptotic pathway [Anatol J Cardiol]
Anatol J Cardiol. 2021; 25(11): 821-828 | DOI: 10.5152/AnatolJCardiol.2021.356

Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress, inflammation, and Caspase 3 apoptotic pathway

Ferhat Dindaş1, Hüseyin Güngör2, Mehmet Ekici3, Pınar Akokay5, Füsun Erhan4, Mustafa Doğduş1, Mehmet Birhan Yılmaz6
1Department of Cardiology, Uşak Training and Research Hospital; Uşak-Turkey
2Department of Pharmacology, Faculty of Veterinary, Cumhuriyet University; Sivas-Turkey
3Department of Physiology, Faculty of Veterinary, Cumhuriyet University; Sivas-Turkey
4Department of Histology, Faculty of Veterinary, Cumhuriyet University; Sivas-Turkey
5Department of Histology, İzmir Kavram Vocational School; İzmir-Turkey
6Department of Cardiology, Faculty of Medicine, Dokuz Eylül University; İzmir-Turkey

Objective: Doxorubicin (DOX) is a well-known cardiotoxic agent, whereas sacubitril/valsartan (Sac/Val) is an effective treatment option in heart failure. In this study, we aimed to evaluate the effect of Sac/Val on DOX-induced cardiotoxicity in pretreatment mice model.
Methods: A total of 24 mice were equally classified into 4 groups; control group, DOX (20 mg/kg; fifth day), Sac/Val (80 mg/kg), and Sac/Val+DOX (Sac/Val was given from day one of the study before doxorubicin administration). Electrocardiography parameters, including durations of QRS, ST, QT, PP segment, and QT/PQ index were measured. Total antioxidant status (TAS), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, NT-proBNP concentrations, and Caspase 3 activity were evaluated.
Results: At the end of the 9-day study duration, QRS, ST, QT intervals, QT/PQ index and TAS, TOS, TNF-α, IL-1β, IL-6 levels were significantly higher in the DOX group than in the control group (p<0.001). Moreover, there were significant differences only in the PP interval when comparing the Sac/Val+DOX and control groups (p<0.001). QRS, ST, QT intervals, and QT/PQ index, TAS, TOS, TNF-α, IL-1β, IL-6 levels were significantly lower in the Sac/Val+ DOX group compared with the DOX group (p<0.001). Furthermore, NT-proBNP levels were lower in the Sac/Val+DOX group compared with the DOX group along with less Caspase 3 apoptosis.
Conclusion: Sac/Val seems to be cardioprotective against DOX-induced cardiotoxicity in pretreatment mice model. These findings can be attributed to the antiarrhythmic, anti-inflammatory, antioxidant, and antiapoptotic effects of Sac/Val as shown in this study.

Keywords: Sacubitril/Valsartan, doxorubicin, cardiotoxicity, heart failure

Ferhat Dindaş, Hüseyin Güngör, Mehmet Ekici, Pınar Akokay, Füsun Erhan, Mustafa Doğduş, Mehmet Birhan Yılmaz. Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress, inflammation, and Caspase 3 apoptotic pathway. Anatol J Cardiol. 2021; 25(11): 821-828

Corresponding Author: Ferhat Dindaş, Türkiye
Manuscript Language: English