Protection of outer hair cells from reperfusion injury by an iron chelator and a nitric oxide synthase inhibitor in the guinea pig cochlea.
To examine whether an active process of the cochlea was injured by ischemia-reperfusion, time courses of distortion-product otoacoustic emissions (DPOAEs) were examined before, during and after 30 min cochlear ischemia using albino guinea pigs. DPOAEs decreased to the minimum level when the animals were subjected to ischemia. When the cochlea was recirculated, DPOAEs initially recovered with time until 20 min after the onset of reperfusion. However, thereafter the amplitude of DPOAEs gradually decreased toward the noise level. Administration of deferoxamine (an iron chelator) or N-nitro-L-arginine (a nitric oxide synthase inhibitor) ameliorated this decrease of DPOAEs during reperfusion and significantly increased the DPOAE amplitudes 60 min after the onset of reperfusion as compared with those in non-treated animals. These results suggest that cochlear reperfusion as well as ischemia injured the active process of the cochlea and that free radicals and nitric oxide play important roles in this injury.
Tabuchi
K
K
Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Okubo
H
H
Fujihira
K
K
Tsuji
S
S
Hara
A
A
Kusakari
J
J
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism*; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D006309:Hearing / Q000187:drug effects / Q000502:physiology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology
D004791:Enzyme Inhibitors; D005609:Free Radicals; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003676:Deferoxamine; D019331:NG-Nitroarginine Methyl Ester