dinoprost and Hearing-Loss--Noise-Induced

Iatrogenic noise produced by mastoid or craniotomy drills may cause hearing damage, which is induced by the generation of reactive oxygen species (ROS) and the reduction of cochlear blood flow (CoBF). This study investigated whether propofol could reduce noise-induced hearing loss (NIHL) in a guinea pig model.. Sixty-four male pigmented guinea pigs were randomly and equally divided into 4 groups: control, noise, propofol and propofol+noise. Propofol was infused intravenously for 20min prior to noise exposure with a loading dose of 5mg·kg. Noise exposure caused decreases in the CoBF and DPOAE amplitudes, over-generation of 8-iso-PGF2α and the loss of OHCs. Pre-treatment with propofol significantly increased the CoBF and DPOAE amplitudes, decreased 8-iso-PGF2α and the loss of OHCs.. Propofol exerted protective effects against NIHL in this animal model by suppressing a lipid peroxidation reaction and improving CoBF.

Topics: Animals; Blood Pressure; Cell Count; Cochlea; Dinoprost; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Guinea Pigs; Hair Cells, Auditory, Outer; Hearing Loss, Noise-Induced; Infusions, Intravenous; Male; Neuroprotective Agents; Noise; Propofol; Random Allocation; Regional Blood Flow; Silver Nitrate

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.

Topics: Acetylcysteine; Acoustic Stimulation; Animals; Auditory Threshold; Cell Count; Cochlea; Dinoprost; Disease Models, Animal; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Evoked Potentials, Auditory, Brain Stem; F2-Isoprostanes; Free Radical Scavengers; Guinea Pigs; Hair Cells, Auditory; Hearing Loss, Noise-Induced; Lipid Peroxidation; Male; NG-Nitroarginine Methyl Ester; Noise; Piperidines; Reactive Oxygen Species; Receptors, N-Methyl-D-Aspartate