Sacubitril/Valsartan Ameliorates Crizotinib-Induced Cardiotoxicity in Mice

Background: Lung cancer is one of the major cause death globally. Crizotinib a first-line drug used in treating non-small-cell lung (NSCLC). However, pathophysiological mechanisms underlying its cardiotoxicity are unknown. This study investigated crizotinib-induced and explored whether this toxicity can be prevented by angiotensin receptor/neprilysin inhibitor sacubitril/valsartan. Methods: Male C57BL/6 mice were randomly divided into three groups: control, crizotinib (40 mg⋅kg-1⋅d-1 for four weeks), + sacubitril/valsartan mg⋅kg-1⋅d-1/60 weeks). Expression genes myocardial tissue detected transcriptomic sequencing, with verification differentially expressed (DEGs) using Real time-polymerase chain reaction (RT-PCR). Blood pressure (BP) cardiac function animals measured non-invasive monitoring echocardiography approaches. Ventricular refractory period (RP), as well induction rate score ventricular arrhythmias (VAs) vivo electrophysiology. Epicardial conductance was mapping. Myh7 myocardium western blot RT-PCR. Results: DEGs sequencing included 10 up-regulated 20 down-regulated genes. The first 5 identified Myh7, Ngp, Lcn2, Ciart Ptgds. Kyoto Encyclopedia Genes Genomes (KEGG) result indicated that involved myocarditis, cardiomyopathy, muscle contraction. treatment increased blood pressure, prolonged QTc interval, shortened RP, incidence right VAs, expression. Most these responses limited Conclusions: induced range cardiotoxic side effects mouse model expression represents biomarker response. These cardiovascular toxic largely