Apelin-13 administration at 40 μg/kg/day reduced apoptotic nuclei and increased apelin-13 and APLNR mRNA expression in a rat model of doxorubicin-induced cardiotoxicity.
Does apelin-13 reduce apoptosis and cardiotoxicity in a rat model of doxorubicin-induced cardiotoxicity?
Apelin-13 demonstrated potential cardioprotective effects against doxorubicin-induced cardiotoxicity by reducing apoptosis in a rat model.
Doxorubicin (DOX) is an anthracycline chemotherapeutic drug used in the treatment of various cancers. Nevertheless, it can cause serious side effects such as cardiotoxicity. Therefore, additional drugs are being searched for to inhibit this effect. Recent studies have shown that the apelinergic system, specifically apelin-13, may have such an impact. However, this hypothesis has not yet been fully investigated. This study aims to assess the potential cardioprotective effect of apelin-13 on doxorubicin-induced cardiotoxicity in the context of apoptosis in male Sprague-Dawley rats. The experiment was conducted on 64 male Sprague-Dawley rats implanted with osmotic pumps on their backs, dosing apelin-13 for the experimental groups and NaCl for the control and positive controls. Cardiotoxicity was induced in rats (except control) by quadruple administration of DOX at a dose of 3.5 mg/kg at weekly intervals. Seven days after the last administration of the chemotherapeutic agent, the rats were sacrificed, and tissues were collected for further analysis. Serum troponin I and tissue apelin-13 concentration were assessed by ELISA. The mRNA expression of apelin-13 and its receptor (APLNR) in heart tissue were quantified by RT-PCR. The terminal 2'-deoxyuridine deoxynucleotidyl transferase assay, labelled with a 5'-triphosphate strand, was used to assess the degree of apoptosis. Pathomorphological changes were assessed by hematoxylin and eosin staining. DOX caused increases in troponin I serum level, confirming its cardiotoxicity. DOX administration decreased apelin-13 and APLNR mRNA gene expression in the rat heart. Administration of apelin-13 at a dose of 40 μg/kg body weight /day significantly increased mRNA expression of both genes. TUNEL staining revealed that the number of apoptotic nuclei was elevated in the DOX-only group compared to the control group. Differences were observed in the group receiving DOX and APLN-13 at low doses (40 μg/kg), and apoptotic nuclei were detected only in some samples. Furthermore, the number of apoptotic cells in samples taken from rats treated with DOX and APLN-13 (200 μg/kg) was elevated compared to the saline group. This was confirmed by histopathological examination. APLN-13 showed potential protective effects against DOX cardiotoxicity. That is why modulation of apelinergic system could be considered as a promising be as parallel therapy in reducing heart complications during and after anthracyclines therapy. Funding: This study was funded by the National Science Centre (NCN), Cracow, Poland, grant number 2020/37/B/NZ5/02529. This abstract was presented at the American Physiology Summit 2026 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.
Cudnoch-Jedrzejewska et al. (Fri,) conducted a other in Doxorubicin-induced cardiotoxicity (n=64). Apelin-13 vs. NaCl (saline) and DOX-only was evaluated on Degree of apoptosis, serum troponin I, and mRNA expression of apelin-13 and APLNR. Apelin-13 administration at 40 μg/kg/day reduced apoptotic nuclei and increased apelin-13 and APLNR mRNA expression in a rat model of doxorubicin-induced cardiotoxicity.