Affiliation:
1. South China University of Technology Department of Ultrasound, Guangzhou First People’s Hospital, School of Medicine, , Guangzhou 510030, Guangdong , China
Abstract
Abstract
We aimed to probe the functions and possible mechanisms of empagliflozin in doxorubicin (Dox)-caused cardiotoxicity. First, a cardiotoxicity rat model was built by continuously injecting Dox intraperitoneally. Then, empagliflozin (30 mg/kg) was gavaged into the rats. Next, echocardiography was utilized for checking the cardiac function of rats, and H&E staining for observing pathological alterations of the myocardial tissues. Besides, biochemical assays and Enzyme-linked Immunosorbent Assay were adopted to detect the creatine kinase isoenzyme (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels in rat serum and superoxide dismutase (SOD), malondialdehyde acid (MDA), and catalase (CAT) in myocardial tissue, respectively. Furthermore, the expression of AMPK/SIRT-1/PGC-1α signaling pathway-related proteins in the myocardial tissues was tested by Western blot. Continuous intraperitoneal injection of Dox greatly elevated left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD), reduced fractional shortening (FS) and ejection fraction (EF), and notably up-regulated CK-MB and NT-proBNP level in rats’ serum, thus impairing cardiac function. Empagliflozin treatment could ameliorate myocardial histopathological damage and alleviate cardiac function and tissue damage by down-regulating LVEDD and LVESD, up-regulating EF and FS, and inhibiting CK-MB and NT-proBNP level in serum. Additionally, empagliflozin improved Dox-induced excessive oxidative stress and dysregulation of energy metabolism. Furthermore, empagliflozin activated the AMPK/SIRT-1/PGC-1α signaling pathway in Dox-caused cardiotoxicity rats. In conclusion, in addition to bettering the cardiac tissue and function injury caused by Dox, empagliflozin also improves excessive oxidative stress and energy metabolism. Notably, empagliflozin may exert cardioprotective effects through activating the AMPK/SIRT-1/PGC-1α pathway.
Publisher
Oxford University Press (OUP)
Subject
Health, Toxicology and Mutagenesis,Toxicology
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献