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).