Ischemia-reperfusion injury of the cochlea: effects of an iron chelator and nitric oxide synthase inhibitors.
Release of free iron from cellular stores and activation of nitric oxide synthase (NOS) has been implicated in a wide variety of cochlear injuries. In order to evaluate the effects of deferoxamine (a iron chelator), 3-bromo-7-nitroindazole (a relatively selective neuronal NOS (nNOS) inhibitor) or aminoguanidine (a relatively selective inducible NOS (iNOS) inhibitor) on the post-ischemic cochlear dysfunction, albino guinea pigs were subjected to 30 min ischemia, and the threshold shifts of the compound action potential (CAP) from pre-ischemic values were compared with those of control animals 4 h after the onset of reperfusion. A statistically significant reduction in the post-ischemic CAP threshold shift was observed in the animals treated with deferoxamine or 3-bromo-7-nitroindazole. However, aminoguanidine did not affect the post-ischemic CAP threshold shift. These results suggest that free iron and nNOS play deleterious roles in the cochlear injury induced by transient ischemia.
Tabuchi
K
K
Department of Otolaryngology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Tsuji
S
S
Asaka
Y
Y
Hara
A
A
Kusakari
J
J
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D007191:Indazoles / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
C106731:3-bromo-7-nitroindazole; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D007502:Iron Chelating Agents; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D003676:Deferoxamine; C004479:pimagedine