Superoxide dismutase-catalase mimetic EUK-134 prevents diaphragm muscle weakness in monocrotalin-induced pulmonary hypertensionReportar como inadecuado




Superoxide dismutase-catalase mimetic EUK-134 prevents diaphragm muscle weakness in monocrotalin-induced pulmonary hypertension - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Patients with pulmonary hypertension PH suffer from inspiratory insufficiency, which has been associated with intrinsic contractile dysfunction in diaphragm muscle. Here, we examined the role of redox stress in PH-induced diaphragm weakness by using the novel antioxidant, EUK-134. Male Wistar rats were randomly divided into control CNT, CNT + EUK-134 CNT + EUK, monocrotaline-induced PH PH, and PH + EUK groups. PH was induced by a single intraperitoneal injection of monocrotaline 60 mg-kg body weight. EUK-134 3 mg-kg body weight-day, a cell permeable mimetic of superoxide dismutase SOD and catalase, was daily intraperitoneally administered starting one day after induction of PH. After four weeks, diaphragm muscles were excised for mechanical and biochemical analyses. There was a decrease in specific tetanic force in diaphragm bundles from the PH group, which was accompanied by increases in: protein expression of NADPH oxidase 2-gp91phox, SOD2, and catalase; 3-nitrotyrosine content and aggregation of actin; glutathione oxidation. Treatment with EUK-134 prevented the force decrease and the actin modifications in PH diaphragm bundles. These data show that redox stress plays a pivotal role in PH-induced diaphragm weakness. Thus, antioxidant treatment can be a promising strategy for PH patients with inspiratory failure.



Autor: Koichi Himori , Masami Abe , Daisuke Tatebayashi, Jaesik Lee, Håkan Westerblad, Johanna T. Lanner, Takashi Yamada

Fuente: http://plos.srce.hr/



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