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Toxicol In Vitro ; 36: 38-45, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27396687

RESUMO

Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2+)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2+) 100-1000µM. The contractile response to Ca(2+) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2+) whereas O2(-) was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2+) influx were impaired only by Fe(2+) 1000µM, and antioxidants had no effect. In skinned fibers, Fe(2+) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2+) sensitivity. These effects are mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000µM, Fe(2+) appears to depress force also by reducing Ca(2+) influx, probably due to a competition at Ca(2+) channels.


Assuntos
Compostos Ferrosos/farmacologia , Contração Miocárdica/efeitos dos fármacos , Músculos Papilares/efeitos dos fármacos , Animais , Cálcio/metabolismo , Técnicas In Vitro , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/fisiopatologia , Contração Isométrica/efeitos dos fármacos , Masculino , Miosinas/metabolismo , Músculos Papilares/metabolismo , Músculos Papilares/fisiologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
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