The effects of tempol, 3-aminobenzamide and nitric oxide synthase inhibitors on acoustic injury of the mouse cochlea.
Oxygen free radicals have been implicated in the pathogenesis of acoustic injury of the cochlea. The purpose of this study was to evaluate the effects of tempol (a superoxide anion scavenger), 3-aminobenzamide (a poly (ADP-ribose) synthetase (PARS) inhibitor), N-nitro-l-arginine (a non-selective nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (a selective neuronal NOS inhibitor) and aminoguanidine (a selective inducible NOS inhibitor) on acoustic injury. Mice were exposed to a 4 kHz pure tone of 110-128 dB SPL for 4h. Tempol, 3-aminobenzamide or N-nitro-l-arginine was intraperitoneally administered immediately before the onset of acoustic overexposure, while 7-nitroindazole or aminoguanidine was intraperitoneally administered every 12h starting immediately before the onset of acoustic overexposure. The threshold shift of the auditory brainstem response (ABR) and hair cell loss were then evaluated one and two weeks after acoustic overexposure. Tempol and 3-aminobenzamide significantly protected the cochlea against acoustic injury, whereas the NOS inhibitors did not exert any protective effect. These findings suggest that reactive oxygen species and PARS are involved in acoustic injury of the cochlea. However, further study is necessary to elucidate the roles of nitric oxide and nitric oxide synthase in acoustic injury.
Murashita
Hidekazu
H
Department of Otolaryngology, Tsukuba University Hospital, Tsukuba, Japan.
Tabuchi
Keiji
K
Hoshino
Tomofumi
T
Tsuji
Shigeki
S
Hara
Akira
A
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001309:Auditory Threshold / Q000187:drug effects; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003051:Cochlea / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control*; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009622:Noise / Q000009:adverse effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013113:Spin Labels
D000975:Antioxidants; D001549:Benzamides; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006146:Guanidines; D007191:Indazoles; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013113:Spin Labels; D019335:Nitroarginine; C025160:3-aminobenzamide; D019001:Nitric Oxide Synthase; C004479:pimagedine; C001803:tempol; C080122:7-nitroindazole