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


Dindas F., GÜNGÖR H., EKİCİ M., Akokay P., ERHAN F., Dogdus M., ...Daha Fazla

ANATOLIAN JOURNAL OF CARDIOLOGY, cilt.25, sa.11, ss.821-828, 2021 (SCI-Expanded, Scopus, TRDizin) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 11
  • Basım Tarihi: 2021
  • Doi Numarası: 10.5152/anatoljcardiol.2021.356
  • Dergi Adı: ANATOLIAN JOURNAL OF CARDIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.821-828
  • Anahtar Kelimeler: sacubitril, valsartan, doxorubicin, cardiotoxicity, heart failure
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), 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-alpha, IL-1 beta, 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-alpha, IL-1 beta, 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.