Oxypurinol, a xanthine oxidase inhibitor and a superoxide scavenger, did not attenuate ischemic neuronal damage in gerbils.
The superoxide (O2.-) scavenging activity and neuroprotective effects of oxypurinol, a xanthine oxidase inhibitor, were compared with those of alpha-phenyl-N-tert-butyl nitrone (PBN). The rate constant for the reaction of oxypurinol with O2.- at pH 7.4 was 1.71 x 10(3) M(-1) s(-1) which was more than 100-fold that of PBN (1.65 x 10 M(-1) s(-1)). Oxypurinol inhibited the release of O2.- from stimulated neutrophils better than did PBN. However, oxypurinol did not attenuate the ischemic neuronal damage in gerbils, while PBN did. These results indicate that neither xanthine oxidase inhibiting activity nor O2.- scavenging activity correlates to the therapeutic efficacy of neuroprotective agents in ischemic-reperfusion injury.
Department of Anesthesia, Kyoto University Hospital, Japan. arai@kuhp.kyoto-u.ac.jp
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Arai
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Mori
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Ishii
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Adachi
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Endo
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Makino
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Mori
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D003497:Cyclic N-Oxides / Q000378:metabolism / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009504:Neutrophils / Q000187:drug effects; D010117:Oxypurinol / Q000494:pharmacology*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D013113:Spin Labels; D013481:Superoxides; C017245:5,5-dimethyl-1-pyrroline-1-oxide; C055956:5,5-dimethyl-5-hydroperoxy-1-pyrrolidinyloxy; D014969:Xanthine Oxidase; D010117:Oxypurinol; D013755:Tetradecanoylphorbol Acetate