Protection from noise-induced lipid peroxidation and hair cell loss in the cochlea.
In order to delineate mechanisms of noise-induced hearing loss, we assessed noise trauma and its pharmacological modulation in the guinea pig. Auditory threshold shifts (measured by auditory brainstem responses), hair cell loss and lipid peroxidation (8-isoprostane formation) were determined in the absence or presence of agents known to influence the formation or action of reactive oxygen species (ROS): the non-specific N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK-801, its inactive isomer (-)-MK-801, the selective NR1/2B NMDA receptor antagonist PD 174494, the nitric oxide synthase (NOS) inhibitor L-N(omega)-Nitroarginine methyl ester (L-NAME) and the anti-oxidant N-acetylcysteine (NAC). (+)-MK-801 and NAC attenuated threshold shifts and hair cell loss effectively while PD 174494 did so partially. L-NAME attenuated threshold shifts at 2 kHz but increased them at 20 kHz, and (-)-MK-801 was ineffective. Noise-induced elevation in 8-isoprostane in the cochlea was significantly attenuated by (+)-MK-801 and PD 174494 in the organ of Corti and modiolar core, by L-NAME in the lateral wall and modiolar core, and by NAC in all three regions. (-)-MK-801 did not influence noise-induced 8-isoprostane formation. There was a significant correlation between threshold shifts at 4 kHz, hair cell loss and the level of 8-isoprostane formed in the organ of Corti, but not in the lateral wall tissues. This finding suggests a causal relationship between ROS formation and functional and morphological damage. NMDA receptors and, to some extent, NOS may be involved in noise-induced ROS formation. The data also indicate that lipid peroxidation in the lateral wall tissues does not influence permanent threshold shifts.
Ohinata
Yoshimitsu
Y
Kresge Hearing Research Institute, The University of Michigan, 1301 East Ann Street, Ann Arbor, Michigan, MI 48109-0506, USA.
Miller
Josef M
JM
Schacht
Jochen
J
D000111:Acetylcysteine / Q000494:pharmacology; D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D002452:Cell Count / Q000379:methods; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D028441:F2-Isoprostanes / Q000032:analysis / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000503:physiopathology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism* / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009622:Noise / Q000009:adverse effects; D010880:Piperidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D028441:F2-Isoprostanes; D016166:Free Radical Scavengers; D010880:Piperidines; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; C075750:8-epi-prostaglandin F2alpha; D016291:Dizocilpine Maleate; D015237:Dinoprost; C120799:PD 174494; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine