Does xanthine oxidase contribute to the hydroxyl radical generation in ischemia and reperfusion of the cochlea?
We investigated the effect of a hydroxyl radical scavenger, 1,3-dimethyl-2-thiourea (dimethylthiourea), and two xanthine oxidase inhibitors, oxypurinol and allopurinol, on the threshold shift of the compound action potential (CAP) after transient ischemia of the cochlea. Transient ischemia of 30 min duration was induced in albino guinea pigs via a skull base approach. The animals were treated with perilymphatic perfusion of dimethylthiourea, oxypurinol or allopurinol from 10 min before the onset of ischemia to 4 h after the termination of ischemia. Dimethylthiourea ameliorated the CAP threshold shifts at 4 h after the onset of reperfusion in a dose-dependent manner. However, oxypurinol and allopurinol did not affect the post-ischemic cochlear dysfunction. These results imply that the hydroxyl radical plays an important role in generation of cochlear dysfunction induced by ischemia-reperfusion and that xanthine oxidase may not be the primary source of this radical.
Tabuchi
K
K
Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Tsuji
S
S
Ito
Z
Z
Hara
A
A
Kusakari
J
J
D000200:Action Potentials / Q000187:drug effects; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D003051:Cochlea / Q000098:blood supply* / Q000293:injuries* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006168:Guinea Pigs; D017665:Hydroxyl Radical / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D010117:Oxypurinol / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D014969:Xanthine Oxidase; D010117:Oxypurinol; D013890:Thiourea