ROLE OF ASCORBATE IN PROTECTION BY NITECAPONE AGAINST CARDIAC ISCHEMIA-REPERFUSION INJURY

The antioxidant properties of nitecapone, a catechol derivative and an inhibitor of catechol-O-methyltransferase, were reported recently. In the present study, the influence of nitecapone on isolated rat heart ischemia-reperfusion injury was investigated to elucidate its cardiopr otective role. Nitecapone, administered in the perfusion buffer from t he beginning of the pre-ischemic phase, significantly improved recover y of cardiac mechanical function, suppressed enzyme leakage in the cor onary effluent, and minimized loss of ascorbate, compared with the con trol group. In rats fed a diet containing 4% ascorbate, myocardial asc orbate content in ascorbate-fed rats after ischemia-reperfusion was hi gher than that in control rats fed a normal diet without ischemia. How ever, supplemented rats did not show any beneficial effects on cardiac mechanical recovery or enzyme leakage, suggesting that maintenance of tissue ascorbate level is not the cause, but the result of the protec tive effects of nitecapone against cardiac ischemia-reperfusion injury . The iron-chelating effect of nitecapone was also tested. It was conf irmed, using electron spin resonance, that 50 mu M nitecapone chelates the same concentration of iron released from the heart into the coron ary effluent. Hence, the iron-chelating ability of nitecapone may be r esponsible, at least in part, for its cardioprotective effects in isch emia-reperfusion injury.