dizocilpine-maleate and Hearing-Loss--Noise-Induced

Noise is a stress factor that causes auditory, psychological and physiological effects. The realization that sudden loud noises or chronic exposure to noise in social and working environments can cause hearing loss has led to increased interest in noise-induced hearing loss (NIHL). The best means of preventing primary damage is protection against noise. Since this protection is not always possible for various reasons, the use of pharmacological agents to prevent or treat NIHL should also be considered. The purpose of this study is to discuss current pharmacological protection and treatment options in the light of the literature, since no such extensive reviews have been performed to date, including agents used for protection against and treatment of NIHL. We reviewed both animal and clinical studies, and these are discussed separately for ease of comprehension. For each agent, first animal studies, then clinical studies, if available, are discussed. We also performed a two-step search of the literature. In the first step, we searched the terms "noise induced hearing loss", "treatment" and "protection" in Pubmed. Based on the results obtained, we identified the agents used for the treatment of and protection against NIHL. In the second step, we searched the names of the agents identified in the first step, together with the term "noise induced hearing loss," and reviewed the results.

Topics: Animals; Antioxidants; Calcium Channel Blockers; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Glucocorticoids; Hearing Loss, Noise-Induced; Humans; Magnesium; Methionine; Nerve Growth Factors; Ubiquinone; Vitamins

To observe the protective effects of MK-801, an antagonist of N-methyl-D-aspartate (NMDA) receptor, against temporary (TTS) or permanent threshold shifts (PTS) in acoustic trauma.. Twenty guinea pigs were exposed to octave band noise with a central frequency of 4 kHz, 110 dB SPL for 3 h, and another twenty guinea pigs, to the same band noise at 115 dB SPL for 5 h. The test animals were given MK-801 (0.5 mg/kg, i. p. ) before and immediately after noise exposure; the control animals were treated with saline solution. Auditory brainstem responses (ABRs) of animals were recorded and ultrastructure of inner hair cells and afferent synapses were examined with transmission electron microscopy.. There was no significant difference in temporary threshold shifts immediately after noise exposure to 110 dB noise between the test and control group. The threshold shifts disappeared in one week after exposure in both groups. In 115 dB group, the threshold shifts of the test animals 7 days after exposure were significantly less than those of the control animals ( P >0.05) and 3 weeks after exposure, there was still this difference. The inner hair cell and afferent dendrites of the control animal exposed to 115 dB noise displayed many vacuoles. No vacuoles, however, were found in the inner hair cells or in the afferent dendrites of animals that were exposed to 110 dB noise or the test animals of 115dB group that received MK-801.. MK-801 could partially protects against PTS, but not TTS in acoustic trauma through preventing from vacuole degeneration in inner hair cell and afferent dendrites.

Topics: Animals; Auditory Threshold; Dizocilpine Maleate; Evoked Potentials, Auditory, Brain Stem; Excitatory Amino Acid Antagonists; Guinea Pigs; Hair Cells, Auditory, Inner; Hearing Loss, Noise-Induced; Male

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

While a clear role has been proposed for glutamate as a putative neurotransmitter at the inner hair cell type I spiral ganglion cell synapse, the possible role of excessive glutamate release in cochlear impairment and of NMDA receptors in such a process is uncertain. The present study compares the protective effects of (+)-MK-801, an NMDA receptor antagonist, and the relatively inactive isomer (-)-MK-801 against permanent noise-induced hearing loss (NIHL). The study also asks whether (+)-MK-801 can protect against the NIHL potentiation by carbon monoxide (CO). Rats (n = 6) were exposed to 100-dB, 13.6-kHz octave-band noise for 2 h after receiving injection of (+)-MK-801 hydrogen maleate (1 mg/kg), (-)-MK-801 hydrogen maleate (1 mg/kg), or saline. Other groups of animals were exposed to the combination of noise and CO (1200 ppm) after receiving (+)-MK-801 or saline. Additional subjects received (+)-MK-801, saline or CO exposure alone. Compound action potential (CAP) threshold sensitivities were compared 4 weeks after the exposures. The results show significant protection by (+)-MK-801 against the permanent CAP threshold elevation induced by noise alone, but no protective effect of (-)-MK-801. (+)-MK-801 produced limited protection against threshold shifts induced by the combination of noise and CO. Outer hair cell (OHC) loss was not protected by (+)-MK-801 administration. The data suggest that NMDA receptor stimulation may play a role in NIHL resulting from fairly mild noise exposure. The data do not support a role for NMDA receptor stimulation in the potentiation of NIHL that results from simultaneous exposure to CO and noise.

Topics: Action Potentials; Animals; Auditory Threshold; Carbon Monoxide; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Hearing Loss, Noise-Induced; Male; Rats; Receptors, N-Methyl-D-Aspartate; Stereoisomerism