The effect of elabela on hemodynamic changes induced by doxorubicin in rats

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Despite the progres in anticancer therapies chemotherapeutics are still one of the key drugs in the pharmacotherapy of this disease. Unfortunately, their use carries various side effects including, the worst, cardiotoxicity, which is particularly prevalent in the anthracycline group. Research is constantly being conducted to reduce these effects by trying to incorporate substances that mitigate these toxic effects, to the ongoing cancer pharmacotherapy. Recently, elabela, APJ receptor ligand, one of key molecule of apelinergic system has received a lot of attention in this field due to its involvement in cardiovascular regulation. The aim of our study was to investigate the ability of elabela to inhibit the toxic effects of anthracycline – doxorubicin (DOX), chronically administered to rats. For this purpose Sprague Dawley adult, male rats were administered intraperitoneal DOX at a dose of 3.5 mg/kg (4 times at a weekly intervals). Simultaneously NaCl or Elabela (40 ug/kg or 200 ug/kg) were releasing from osomotic pumps implanted on the first day of the experiment for the treated group throughout the experiment. On the first and last day, elelctro cardiographic (ECG) and echocardiographic (ECHO) measurements were performed. Both ECG and ECHO examination confirmet cardiotoxicity of DOX chronic administration by showing QT and QTc interval prolongation and decreased left ventricular ejection fraction (LVEF), fractional shortening (FS), stroke volume (SV) and cardiac output (CO) in DOX-treated group vs, healthy control, respectively. This data indicate DOX-induced left ventricular systolic dysfunction. Furthermore, results of our study showed that the simultaneous administration of elabela at a dose of 40 µg/kg released continuously for 28 days from implanted osmotic pumps, prevent DOX-induced prolongation of QT and QTc intervals. Moreover, ECHO examination indicated improvement in LV systolic parameters in form of increase in EF, FS, SV, CO in DOX-treated groups receiving simultaneously elabela. The higher dose of elabela (200 ug/kg) did not showed cardioprotective effect. This may be due to the toxicity of hyperstimulation of the apelin/β-arrestin-APJ axis or β-arginine-mediated internalization of the APJ and eventual desensitization of this receptor. To conclude, our research indicate that elabela has ability to inhibits the hemodynamic changes induced by chronic administrtation od DOX. This research was funded by National Science Centre (NCN), Kraków, Poland, grant number 2020/37/B/NZ5/02529 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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