Protective effects and mechanisms of lycorine against adriamycin-induced cardiotoxicity

Adriamycin (ADR), a high-efficiency, broad-spectrum anthraquinone chemotherapeutic agent, is currently used to treat various malignant tumors and can lead to cumulative, dose-dependent, and irreversible cardiotoxicity. Lycorine (LYC) is a benzyl phenethylamine alkaloid that exerts remarkable therapeutic effects on cancers and sepsis.However, researchers have not yet elucidated whether LYC exerts protective effects against cardiotoxicity induced by ADR and the possible molecular mechanisms.This study established ADR injury models in vitro and in vivo to explore the effects of LYC against cardiotoxicity induced by ADR. The effects of LYC on blood biochemical parameters, cardiac parameters and structure, ADR-related pathophysiological processes, and the SIRT1/PPARγ signal pathway in ADR-injured models, were analyzed using a series of experimental methods.LYC significantly improved survival rate, blood biochemical parameters (LDH, CK, and BUN), cardiac parameters (SV and CO), mitochondrial dysfunction, and ameliorated oxidative stress, apoptosis, and myocardial fibrosis in ADR-injured mice (p<0.05). Moreover, LYC obviously increased cell viability and reduced oxidative stress, apoptosis, and mitochondrial dysfunction in ADR-injured cells (p<0.05). Furthermore, this study confirmed that the protective effect of LYC on ADR-induced cardiotoxicitymight be mediated by the SIRT1/PPARγ signaling pathway. These results revealed that the beneficial role of LYC on cardiotoxicity induced by ADR were mediated via regulating SIRT1/PPARγ signaling for the first time.These discoveries may provide a theoretical basis for the exploitation of LYC as a potential cardioprotective drug candidate due to its multiple biological functions to reduce ADR-induced cardiotoxicity, but further preclinical and clinical studies are still needed.