OXYPURINOL, A XANTHINE-OXIDASE INHIBITOR AND A SUPEROXIDE SCAVENGER, DID NOT ATTENUATE ISCHEMIC NEURONAL DAMAGE IN GERBILS

The superoxide (O-2(.-) scavenging activity and neuroprotective effect s of oxypurinol, a xanthine oxidase inhibitor, were compared with thos e of alpha-phenyl-N-tert-butyl nitrone (PBN). The rate constant for th e reaction of oxypurinol with O-2(.-) at pH 7.4 was 1.71 X 10(3) M-1 s (-1) which was more than 100-fold that of PEN (1.65 X 10 M-1 s(-1)). O xypurinol inhibited the release of O-2(.-) from stimulated neutrophils better than did PEN. However, oxypurinol did not attenuate the ischem ic neuronal damage in gerbils, while PEN did. These results indicate t hat neither xanthine oxidase inhibiting activity nor O-2(.-) scavengin g activity correlates to the therapeutic efficacy of neuroprotective a gents in ischemic-reperfusion injury. (C) 1998 Elsevier Science Inc.