RESUMO
BACKGROUND: 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. PURPOSE: However, researchers have not yet elucidated whether LYC exerts protective effects against cardiotoxicity induced by ADR and the possible molecular mechanisms. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Cardiotoxicidade , Doxorrubicina , Alcaloides de Amaryllidaceae , Animais , Cardiotoxicidade/tratamento farmacológico , Camundongos , Estresse Oxidativo , PPAR gama , Fenantridinas , Sirtuína 1RESUMO
Dangguibuxue decoction (DBD), a kind of Chinese herbal medicine, has been widely used to treat blood deficiency disease in China. In this experiment, we studied the effects of the Dangguibuxue decoction (DBD) on the myocardial injury induced by cyclophosphamide in mice. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and lactic dehydrogenase (LDH) in serum were detected by commercial kits. Total white blood cell (WBCs), platelets, and cytokines pathological changes of heart tissue were also examined. In addition, the protein levels of the NF-кB pathway were detected to reveal its mechanism. The results showed that DBD significantly decreased the levels of ALT, AST, CK, and LDH and increased WBCs in CTX-induced mice. In addition, DBD significantly alleviated pathological changes of heart tissue. DBD significantly reduced the protein expressions of NF-кB signaling pathway. In summary, DBD can be considered an effective drug to alleviate CTX-induced heart damage in mice.