Comparison of the prophylactic effects of apelin, sacubitril/valsartan and combination in doxorubicin-induced heart failure in rats

Aim: HF is a clinical syndrome caused by structural/functional disorders in the myocardium, resulting in impaired ventricular filling or ejection fraction. In our study, it was aimed to compare the prophylactic effects of apelin, SV and their combination, which are known to have positive effects in CVD in HF. Material and Method: In the study, a total of 50 male Sprague Dawley rats aged 4 months (250-300 g) were simple randomized single-blind assigned to Control (n=8), Dox (n=12), Apelin+Dox (n=10), SV+Dox (n=10) and Apelin+SV+Dox (n=10) groups. The HF model was induced by ip administration of Dox at a rate of 6X2.5 mg/kg (15 mg/kg) over a two-week period. In the same period, 20 nmol/kg/day apelin was administered ip to the Apelin group, 68 mg/kg/day SV to the SV+Dox group periorally, and apelin, SV and Dox to the Apelin+SV+Dox group. ECHO and invasive hemodynamic measurements were performed at the end of the experiment. Heart, aortic tissue and blood were collected and histopathologically and ELISA were studied. Results: There was an improvement in heart weight in the Apelin+SV+Dox group, a decrease in mortality in the SV+Dox and Apelin+SV+Dox groups, and a decrease in heart rate in both groups given SV compared to the control group. A decrease in systolic blood pressure was observed in the Dox, SV+Dox and Apelin+SV+Dox groups. Diastolic and mean blood pressure were decreased in both SV+Dox and Apelin+SV+Dox groups. There was a decrease in LVEF and LVFS in the Dox group, and an increase in the SV+Dox and Apelin+SV+Dox groups. Degenerated cardiomyocyte, vacuolization, hemorrhage, infiltration, collagen increase, MMP-2 and MMP-9 increase were observed in the Dox group, while improvements were observed in all prophylactic groups. No significant change was observed in biochemical results. Conclusion: It was found that Apelin, SV and the combination, especially SV, provided significant improvements in ECHO and histopathologically in Dox-induced heart failure. Further studies are needed to support our results. Keywords: Doxorubicin, apelin, sacubitril/valsartan, heart failure, ejection fraction, rat