EFFECTS OF SELENIUM DEFICIENCY ON DIAPHRAGMATIC FUNCTION AFTER RESISTIVE LOADING

Diaphragmatic fatigue has been associated with increased production of reactive oxygen species. Among the defences against reactive oxygen s pecies is the glutathione redox system. The selenium-dependent enzyme glutathione peroxidase is an important component of this system. Thus, we hypothesized that selenium deficiency would lower glutathione pero xidase activity and render the diaphragm more susceptible to a mild ex ertional protocol. Sprague-Dawley rats were fed a selenium-deficient o r control diet for 12 weeks then divided into four experimental groups : (1) unloaded, basic diet with selenium supplementation (control); (2 ) unloaded, selenium-deficient diet, (3) loaded, basic diet with selen ium supplementation; and (4) loaded, selenium-deficient diet. Diaphrag matic in vitro contractile properties, glutathione peroxidase activity and glutathione content were measured. During inspiratory resistive l oading, the animals breathed against an inspiratory resistor at 70% of maximal airway pressure until the target pressure was not achieved fo r five consecutive breaths. Selenium deficiency resulted in a signific ant decrease in diaphragmatic glutathione peroxidase activity, without changes in total glutathione content. Neither selenium deficiency nor inspiratory resistive loading alone impaired diaphragmatic contractil ity. Selenium deficiency in conjunction with inspiratory resistive loa ding resulted in a significant decrease in diaphragmatic twitch and te tanic force, with a downward shift in the force/frequency curve. These data suggest that selenium deficiency lowers diaphragmatic glutathion e peroxidase activity, and when these animals are subjected to the oxi dative stress of resistive loading, there is an impairment in muscle f unction. We conclude that a functional glutathione peroxidase is neces sary to protect the diaphragm against the effects of resistive loading .