4.1 Animal experimental models
Researches as the performance of sacubitril/valsartan against
doxorubicin-induced cardiotoxicity are rare in animal experimental
models. Deteriorative heart function, inordinate mitochondrial structure
and respiratory function were found after managed with doxorubicin,
which could be markedly alleviated by sacubitril/valsartan treatment in
mice (33). The protective action of sacubitril/valsartan on
doxorubicin-related heart dysfunction was related to the improvement of
fission protein dynamin-related protein 1 (Drp1)-mediated mitochondrial
dysfunction in some degree (33). Sacubitril/valsartan could attenuate
doxorubicin-related heart failure and arrhythmia in a prophylactic
treatment mice model by inhibiting oxidant stress damage, inflammatory
response and apoptosis (34). Sacubitril/valsartan provided greater
protection against doxorubicin-induced cardiac systolic dysfunction and
LV remodeling by downregulating matrix metalloproteinase (MMP) activity
in rats (35). Furthermore, endoplasmic reticulum stress (ERS) was one of
the key pathogenesis of doxorubicin-related heart failure.
Sacubitril/valsartan markedly improved doxorubicin-related cardiac
dysfunction by downregulating the protein expression associated with ERS
and apoptosis in a rat model (36).