Potential protective role of apelin-13 in the doxorubicin-induced cardiotoxicity in the rat

Abstract

Due to its unselective action, chemotherapy affects not only cancer cells but also a variety of normal human cells causing several toxicities, thus leading to decreased anticancer efficacy. One of such toxicities is cardiotoxicity caused by anthracyclines, mainly doxorubicin (DOX). Doxorubicin-induced cardiotoxicity (DIC) generally occurs as a chronic process and resembles chronic heart failure with reduced ejection fraction. Based on the data about the role of the apelinergic system in the pathogenesis of cardiovascular diseases like heart failure, we hypothesize that it can be also involved in the DIC. Dysregulation of the apelinergic system has been observed in heart failure or myocardial infarction, which was confirmed in studies when apelinergic stimulation resulted in a cardioprotective effect.The aim of the present study was to investigate the role of apelin-13 on echocardiographic parameters in the DIC in the rat.The study was performed in a rat model (male Sprague Dawley, 12 weeks old) of cardiotoxicity. The animals were randomly divided on 3 groups (control, DOX, apelin 40 μg/kg). The cardiotoxicity was induced by 4 intraperitoneal injections of DOX in a dose of 3,5 mg/kg every 7 days with control group receiving saline. All animals were implanted with osmotic pumps to receive a continuous infusion of apelin-13 or saline (control) for 4 weeks, concomitantly with DOX. Immediately before the first dose echo examination was performed. The same procedure was repeated on day 28 days after the last dose of DOX. Later, animals were euthanized and heart samples were collected.Echocardiographic parameters in DOX group compered to control group showed left ventricle (LV) systolic dysfunction, with significant deterioration of LV ejection fraction (LVEF) (66±2.55% vs. 90±4.88), fractional shortening (%FS) (31,67±2.2% vs 55,33±4.45), stroke volume/tibial length ratio (0.041±0.008ml/cm vs 0.064±0.02), and cardiac output/tibial length ratio (10.35±2.12ml/min/cm vs 17.04±4.08). Apelin-13 at a dose of 40 μg/kg reduced the toxic effects of DOX. Furthermore, the heart weight in the group with DOX was significantly smaller than in the control group, while in the group receiving continuous infusion of apelin-13 at a dose 40 μg/kg the heart weight was very similar to control group.The results indicate that continuous exposure to apelin-13 in dose 40 μg/kg has a cardioprotective effect in echocardiographic and clinical parameters. Evaluating the role of the apelinergic system will help us to better understand the pathomechanisms of cardiotoxicity and in the future may result in the development of protective or curative therapies. Acknowledgments: This study was supported by the Grant No UMO-2020/37/B/NZ5/02529 from the National Science Center (Poland). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.