Protective Effects And Mechanisms Of Lycorine Against Adriamycin-Induced Cardiotoxicity

Adriamycin(ADR),a anthraquinone chemotherapeutic agent,is currently used to treat various malignant tumors and can lead to cumulative and dose-dependent 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 beneficial effects on ADR-induced cardiotoxicity and the underlying mechanisms.This study established ADR injury models in BALB/c mice and HL-1 cardiomyocytes to investigate the effects of LYC on ADR-induced cardiotoxicity.A series of experimental methods were used to evaluate the effects of LYC on cardiac function indicators,blood biochemical parameters,histopathology,oxidative stress,apoptosis,mitochondrial function,fibrosis,and the silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor γ(PPARγ)signaling pathway in ADR-injured models.LYC significantly improved survival rate,cardiac function indicators(SV and CO),blood biochemical parameters(LDH,CK,and BUN),and mitochondrial dysfunction and reduced the degree of myocardial fibrosis,oxidative stress and apoptosis in ADR-injured mice(P<0.05).Moreover,in ADRinjured HL-1 cells,LYC obviously increased cell viability and ameliorated oxidative stress,apoptosis,and mitochondrial dysfunction(P<0.05).This study confirmed that the protective effect of LYC on ADR-induced cardiotoxicity might be mediated by the SIRT1/PPARγsignaling pathway.These data revealed that the beneficial effects of LYC on ADR-induced cardiotoxicity were mediated by activating SIRT1/PPARγ signaling for the first time.These findings may provide a theoretical basis for the exploitation of LYC as a protective drug against doxorubicin cardiotoxicity and further expand the application of ADR in oncotherapy.