Table 3.
ARNi administration in animal models of anthracycline-induced cardiotoxicity.
| Paper by | Animal Model | Groups + Dosage (mg/kg/d) | Other Findings (Presented in Comparison to DOX + Vehicle Groups) |
|---|---|---|---|
| Boutagy [127] | Wistar rats |
DOX + Vehicle DOX + ARB 31 DOX + ARNi 68 |
↑ LVEF in ARNi ↓ Myocyte vacuolation in ARNi and ARB ↓ Myocardial fibrosis in ARNi and ARB at 4 wks (no longer seen at 6 wks) ↓ Capillary density in ARNi at 6 wks ↓ Matrix metalloproteinases activity in ARNi at 4 wks ↓ Myocyte CSA and heart weight in all DOX-receiving groups No differences in cellular apoptosis between groups |
| Dindas [128] |
Balb-c mice | Vehicle ARNi 80 DOX + Vehicle DOX + ARNi 80 |
↓ Degenerative changes and streaking in cardiomyocytes in DOX + ARNi ↓ QRS duration, ST interval and QT/PQ index in DOX + ARNi ↓ NT-proBNP, TNFα, IL1β, IL6, and caspase 3 in DOX + ARNi ↓ Total oxidant status and ↑ total antioxidant status in DOX + ARNi |
| Kim [129] |
Sprague Dawley rats | Vehicle DOX + Vehicle DOX + ARNi 60 |
↓ Cardiomyocyte apoptosis in ARNi ↓ Endoplasmic reticulum stress in ARNi ↓ Serum cardiac troponin I and NT-proBNP levels in ARNi group |
| Maurea [133] | C57Bl/6 mice | Sham Sac/Val 60 DOX DOX + Sac/Val 60 |
ARNi improved EF and prevented the reduction of radial and longitudinal strain ↓ Cardiac expression of NLRP3, MyD88, DAMPs, and NF-kB in ARNi ↑ Expression of phosphorylated AMPK in ARNi ↓ Levels of Calgranulin S100 and galectine-3 in ARNi |
| Miyoshi [130] | Sprague Dawley rats | DOX + Vehicle DOX + Val 31 DOX + ARNi 68 |
No differences in LVEF and FS between groups. ↑ Cardiomyocyte CSA and ↑ cardiac fibrosis in ARNi ↑ Cardiac TNFα and ANP mRNA expression in ARB and ARNi ↓ Myocardial collagen I mRNA expression in ARNi ↓ Cardiac troponin T and NT-proBNP levels in ARNi ↓ Cardiac reactive oxygen species levels in ARNi ↑ Phosphorylation of AMPK and ↑ Bax/Bcl-2 ratio in ARNi |
| Xia [131] |
Balb-c mice | Vehicle DOX + Vehicle DOX + ARNi 80 |
↓ Cardiac hypertrophy, myocardial fibrosis and cellular apoptosis in ARNi ↓ Heart weight/body weight and ↑ heart weight/tibial length in ARNi ↑ Single cardiomyocyte contractile function in ARNi ↓ Pathologic changes to mitochondria and ↓ Drp1 expression in ARNi ↓ Cleaved caspase 3 in ARNi |
| Ye [48] |
C57BL/6 mice | Vehicle DOX + Vehicle DOX + ARNi 60 TLR2 KO + Vehicle TLR2 KO + DOX |
↑ LVEF in ARNi, TLR2 KO, and TLR2 KO + DOX ↓ Ventricular wall thinning and ↓ heart cavity enlargement in ARNi and TLR2 KO ↓ Myocardial fibrosis in ARNi and TLR2 KO ↓ Myocardial collagen I and TGFβ protein levels in ARNi and TLR2 KO ↓ Myocardial TNFα and NF-κB levels in ARNi and TLR2 KO |
| Yu [132] |
New Zealand white rabbits |
Vehicle DOX + Vehicle DOX + ARNi 5 DOX + ARNi 10 |
↓ PR segment, QRC segment prolongation, QT interval and QT/PQ index in both ARNi groups ↓ Serum BNP level in ARNi groups ↑ Activity of superoxide dismutase and catalase and ↓ lipid peroxidation in both ARNi groups |
Abbreviations: AMPK—adenosine monophosphate-activated protein kinase; ANP—atrial natriuretic peptide; ARB—valsartan; ARNi—sacubitril/valsartan; BNP—brain natriuretic peptide; CSA—cross-sectional area; DOX—doxorubicin; Drp1—dynamin-related protein 1; KO—knockout; IL—interleukin; LVEF—left ventricle ejection fraction; NF-κB—nuclear-factor kappa-light-chain-enhancer of activated B cells; NLRP3—NLR family pyrin domain containing 3; NT-proBNP—N-terminal prohormone of brain natriuretic peptide; MyD88—myeloid differentiation primary response 88; TGFβ—transforming growth factor β; TNFα—tumor necrosis factor α; wks—weeks. Symbols: ↑/↓—significantly increased/decreased.