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Métodos Terapêuticos e Terapias MTCI
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J Cell Mol Med ; 23(8): 5715-5727, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31225721

RESUMO

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'-deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress-dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after-surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin-treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post-AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiomegalia/tratamento farmacológico , Desoxiadenosinas/uso terapêutico , Transdução de Sinais , Angiotensina II/farmacologia , Animais , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Desoxiadenosinas/farmacologia , Fibrose , Hemodinâmica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Pressão , Transdução de Sinais/efeitos dos fármacos
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