Protective effect of the superoxide scavenger EUK8 against ultrastructural alterations induced by ischemia and reperfusion in isolated rat hearts.

We have recently shown that iron overload may increase the susceptibility of isolated rat hearts to ischemia and reperfusion, an effect that could be related to an iron-dependent activation of the Fenton reaction, thus producing cytotoxic hydroxyl radicals. The purpose of our study was to investigate the influence of EUK8, a new catalytic scavenger of superoxide anions that is similar to superoxide dismutase, on cardiac ultrastructural alterations associated with reperfusion. Experiments were carried out ex vivo in iron-overloaded rat hearts perfused at a constant flow rate (11 ml/min) with (EUK8) or without (control) EUK8 (50 mumol/L) throughout the perfusion. Hearts were submitted to 15 min global normothermic no-flow ischemia and then reperfused for 15 min before examination. For each heart, six micrographs at a magnification of x 11,300 were used to quantitate ultrastructural alterations. In our experimental model, EUK8 prevented some of the ultrastructural modifications associated with ischemia and reperfusion in iron-overloaded rat hearts. This beneficial effect could be related to the limitation of reperfusion-induced oxygen free radical production under the effect of EUK8.