LCZ696 Ameliorates Isoproterenol-Induced Acute Heart Failure in Rats by Activating the Nrf2 Signaling Pathway

OBJECTIVE: LCZ696 (sacubitril/valsartan) is an angiotensin II (Ang II) type 1 receptor-neprilysin inhibitor, with effects of immunosuppression, anti-inflammation, antiapoptosis, and antioxidation. The present study was aimed at determining whether LCZ696 has a protective effect against isoproterenol-induced acute heart failure (AHF) in rats. METHODS: SD rats were randomly divided into four groups: control group, HF group, LCZ696 group, and enalapril group. The cardiac function of rats was evaluated using echocardiographic parameters, heart weight (HW), serum levels of cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). HE is staining, which was used to determine the pathological damage of rat myocardial tissue. Also, we measured oxidative stress markers including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Finally, the expression of Nrf2 signaling pathway-related proteins was determined using Western blot. RESULTS: Compared with the HF group, LCZ696 could significantly improve cardiac function and myocardial injury in rats and reduce AHF-induced oxidative stress. In addition, the results of Western blot confirmed that LCZ696 could upregulate the expression of Nrf2 and HO-1 while decreasing Keap1 expression. CONCLUSION: LCZ696 ameliorates isoproterenol-induced AHF in rats by alleviating oxidative stress injury and activating the Nrf2 signaling pathway.