RESUMO
Hydrogen sulfide (H(2)S), as an endogenous gas signaling molecule with important biological function that has been found recently, may play a protection in ischemic reperfusion (I/R) myocardium. We investigated the cardioprotective effect of H(2)S in rats model of ischemic reperfusion in vivo and a probably influence on the expression of survivin, an anti-apoptosis gene. Animals were randomly divided into 3 groups and received either vehicle, sodium hydrosulfide (NaHS) or DL-propargylglycine (PAG) respectively everyday for 1 week before surgery and the treatment continued for a further 2 d after I/R till the animals were sacrificed. We investigated the plasma H(2)S concentration and blood pressure, with the electrocardiogram (ECG) together, to prove the effect of H(2)S to the heart function. We also compared the heart infarct size and the expression of an anti-apoptosis gene, survivin, among groups. As the data shown, the NaHS group had great improvement in blood pressure and electrocardiogram situation. And the remarkable shrink of the infarct size and up-regulation of survivin in NaHS group comparing with the other two groups also showed the cardio protective effect of H(2)S in our study.
Assuntos
Cardiotônicos/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Sulfeto de Hidrogênio/sangue , Proteínas Associadas aos Microtúbulos/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Sulfetos/uso terapêutico , Alcinos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Western Blotting , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacocinética , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/metabolismo , Modelos Animais de Doenças , Eletrocardiografia , Glicina/análogos & derivados , Glicina/farmacologia , Imuno-Histoquímica , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/enzimologia , Miocárdio/patologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfetos/administração & dosagem , Sulfetos/farmacocinética , SurvivinaRESUMO
AIM: To investigate the effects of deferiprone on doxorubicin-induced cardiotoxicity and determine its protection on cardiac contractility in vivo at tissue level. METHODS: Spontaneously-beating isolated atria from rats were pretreated with deferiprone for 10 min at 1.2 mmol/L or 0.3 mmol/L, respectively before co-incubation with doxorubicin (DOX) at 0.03 mmol/L for 60 min. Contractility (dF/dt) was assessed every 10 min during the incubation. After that, the tissues around the sinuatrial nodes were fixed for ultrastructural study; succinate dehydrogenase (SDH) and Cu, Zn superoxide dismutase (Cu, Zn-SOD) activity, as well as malondialdehyde (MDA) level of the atria were assayed. RESULTS: Treatment with DOX alone resulted in a 49.34% reduction of the contractility, mitochondria swelling, disruption of mitochondrial crista and decreased electron density of the matrices. Conversely, with the presence of deferiprone, the negative inotropic effect and lesions in the cardiac mitochondria structure induced by DOX were attenuated. Cu, Zn-SOD activity increased by 12.97%-12.11%, the MDA level decreased by 29.12%-39.82% and succinate dehydrogenase (SDH) activity was ameliorated by 25.15%-34.76%. CONCLUSION: Deferiprone can efficiently preserve cardiac contractility. Moreover, the results of this study indicate that deferiprone is able to protect mitochondrial function and structure form damage induced by DOX. This cardiac protective potential of deferiprone could be due to its defense capability against oxidative damage.
