Radical scavenging properties of novel benzopyran derivatives, TA248 and TA276, and effects of the compounds on ischemic/reperfused myocardium in dogs

Characteristics of novel benzopyran derivatives, TA248 and TA276, and their effects on myocardial contraction in ischemic/reperfused hearts in dogs we re examined. TA248 and TA276 inhibited NADPH-dependent lipid peroxidation i nduced by Fe3+ in the rat brain homogenate. Both compounds reduced . O-2(-) produced by xanthine-xanthine oxidase system in a dose-dependent manner. T A276 scavenged OH generated by Fenton reaction in a dose-dependent manner. TA248 also inhibited the OH production, but the effect was neither complete nor dose dependent. Myocardial contraction was assessed as segment shorten ing of the left ventricular wall in pentobarbital-anesthetized open-chest d ogs. The segment shortening was decreased by the left anterior descending c oronary artery ligation (ischemia) and returned by release of the ligated a rtery (reperfusion). The segment shortening did not recover fully during, r eperfusion. Either TA248 or TA276 injected 10 min before ischemia improved the recovery of myocardial contraction during reperfusion. Both compounds p reserved the level of ATP in the 60-min reperfused myocardium. However, the level of lipid peroxides was not changed by TA248 and TA276. TA248 and TA2 76 may protect myocardium against ischemic/reperfusion insult, partly becau se of their free radical scavenging activity, but no significant change in myocardial lipid peroxide level was observed. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89. 1114-1122, 2000.