RESUMO
CONTEXT: The serious side effect of Adriamycin (ADR) is cardiomyopathy. Cryptotanshinone (CRY) is widely and safely used as antioxidant with MTD more than 5 mg/g in rats (p.o). OBJECTIVE: The objective of this study is to study the protection effects of CRY against ADR-induced mitochondrial dysfunction in cardiomyocytes. MATERIALS AND METHODS: The chemical administration lasted for 20 days with an effective dose of CRY (p.o.) at 50 mg/kg in rats. Mitochondrial respiratory chain complex activities, ATP generation, mitochondrial membrane potential (MMP), superoxide anion free radical, oxidative stress-relative enzymes, and mitochondrial biogenesis-relative factors in normal control, ADR (i.p., 1.25 mg/kg), and ADR (i.p., 1.25 mg/kg) + CYP (p.o., 50 mg/kg) groups were detected. RESULTS: 50 mg/kg CRY significantly promoted the energy production of ATP (16.99 ± 2.38 nmol/g Pro) (Pro: Protein) by increasing the complexes activities except II (p > 0.05). After the treatment of CRY, the suppressed MMP was increased while superoxide anion free radical (0.57 ± 0.07/mg Pro) was inhibited markedly. Mitochondrial biogenesis-relative factors PGC-1α, NRF-1, and TFAM were also promoted. Remarkable augmentations of NO, inducible nitric oxide synthase (iNOS), and increased activity of GSH-PX (p < 0.05) were also detected after the treatment of CRY, while no obvious changes on the activity of nitric oxide synthase (cNOS; p > 0.05) were observed. DISCUSSION AND CONCLUSION: These results suggest that CRY protects against ADR-induced mitochondrial dysfunction in cardiomyocytes. It could be an ideal potential drug of cardioprotection.
Assuntos
Cardiomiopatias/prevenção & controle , Doxorrubicina/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fenantrenos/uso terapêutico , Trifosfato de Adenosina/metabolismo , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/metabolismo , Cardiotoxicidade/prevenção & controle , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Ratos Wistar , Salvia miltiorrhiza/químicaRESUMO
Cryptotanshinone is one of the compounds extracted from the root of Salvia miltiorrhiza Bunge. Unlike other tanshinones, only a small number of studies have focused on cryptotanshinone for medical treatment. In the present study, the A549 lung cancer cell line and xenograft models of human lung tumors were used to assess the anti-cancer effect of cryptotanshinone. The effect of cryptotanshinone on human lung cancer, including growth inhibition, cell cycle arrest and apoptosis factors, were identified in vitro, and inhibition of tumor formation, improvement of body condition as well as pathological apoptotic effects were detected in vivo. These results suggested that cryptotanshinone is a potential drug for the treatment and prevention of human lung cancer.