Linked Life Data

17722114

Source:http://linkedlifedata.com/resource/pubmed/id/17722114

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-21
pubmed:abstractText
We recently showed that acute energy failure in the rat cochlea induced by local administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) causes hearing loss mainly due to degeneration of cochlear lateral-wall fibrocytes. In the present study, we analyzed the effect of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (Z-VAD-FMK) on 3-NP-induced hearing loss in a model showing temporary threshold shifts at low frequencies and permanent threshold shifts at high frequencies. The model rats received an intraperitoneal injection of either Z-VAD-FMK or vehicle for 3 days starting 1 day prior to 3-NP treatment. One day after the administration of 3-NP, the auditory brain-stem response (ABR) threshold at 20 kHz was elevated to 70 dB in the Z-VAD-FMK group and to 85 dB in controls. The Z-VAD-FMK group completely recovered to the preoperative level within 14 days, whereas in the controls, the ABR threshold remained elevated at 50 dB even 28 days after the administration of 3-NP. Treatment with Z-VAD-FMK also improved recovery of hearing at 8 kHz but did not change recovery at 40 kHz. Histological examination demonstrated that treatment with Z-VAD-FMK inhibited progressive degeneration of the lateral-wall fibrocytes in the cochlear basal turn, as well as apoptosis of these fibrocytes. These results clearly indicate that caspase-dependent apoptosis of fibrocytes in the cochlear lateral wall plays an important role in hearing loss in the present animal model. Moreover, the results of the present study suggest that systemic administration of a caspase inhibitor may be an effective therapy for sensorineural hearing loss caused by acute energy failure such as that observed in cochlear ischemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
215-22
pubmed:meshHeading
pubmed-meshheading:17722114-Acoustic Stimulation, pubmed-meshheading:17722114-Amino Acid Chloromethyl Ketones, pubmed-meshheading:17722114-Animals, pubmed-meshheading:17722114-Apoptosis, pubmed-meshheading:17722114-Auditory Threshold, pubmed-meshheading:17722114-Caspase 3, pubmed-meshheading:17722114-Cochlea, pubmed-meshheading:17722114-Disease Models, Animal, pubmed-meshheading:17722114-Dose-Response Relationship, Radiation, pubmed-meshheading:17722114-Evoked Potentials, Auditory, Brain Stem, pubmed-meshheading:17722114-Gene Expression Regulation, pubmed-meshheading:17722114-Hearing Loss, Sensorineural, pubmed-meshheading:17722114-Male, pubmed-meshheading:17722114-Neuroprotective Agents, pubmed-meshheading:17722114-Nitro Compounds, pubmed-meshheading:17722114-Propionic Acids, pubmed-meshheading:17722114-Rats, pubmed-meshheading:17722114-Rats, Sprague-Dawley, pubmed-meshheading:17722114-Recovery of Function, pubmed-meshheading:17722114-Spiral Ganglion, pubmed-meshheading:17722114-Time Factors
pubmed:year
2008
pubmed:articleTitle
Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction.
pubmed:affiliation
Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't