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Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of endotoxin.
MedLine Citation:
PMID:  22326209     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Oxytetracycline and ilomastat are inhibitors of matrix metalloproteinases (MMPs). Their efficacy in protecting against cochlear damage induced by the intratympanic instillation of lipopolysaccharide (LPS), as a means of inducing labyrinthitis, was investigated. MATERIALS AND METHODS: Experiments were performed in 21 young male guinea pigs. Intratympanic instillation of LPS was done in the control group (n=7). Intratympanic instillation of oxytetracycline or ilomastat was done after LPS instillation in the experimental group. Measurements of auditory brainstem response (ABR) and cochlear blood flow (CBF) were performed. The organ of Corti was evaluated by field emission scanning electron microscopy (FE-SEM). The blood-labyrinth barrier (BLB) integrity was evaluated with Evans blue uptake. Gelatin zymography was used to assess the expression of active MMP-2 and MMP-9. RESULTS: Ears treated with MMP inhibitors were significantly protected from hearing loss compared to the LPS group. In LPS group, there was a significant decrease of CBF. However, experimental group displayed a statistically significant recovery of CBF. FE-SEM revealed hair cell damage in the LPS-treated group, but hair cells presented a normal appearance in MMP inhibitors. The LPS group showed a marked increase of Evans blue extravasation in the cochlea. However, MMP inhibitors significantly reduced the BLB opening. Active MMP-9 was expressed in the LPS group. Treatment with MMP inhibitors attenuated active MMP-9 expression. CONCLUSION: The MMP inhibitors oxytetracycline and ilomastat protect from cochlear lateral wall damage caused by LPS-induced labyrinthitis.
Authors:
Cheol Hee Choi; Chul Ho Jang; Yong Bum Cho; Si Young Jo; Min Young Kim; Byung Young Park
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-10
Journal Detail:
Title:  International journal of pediatric otorhinolaryngology     Volume:  -     ISSN:  1872-8464     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8003603     Medline TA:  Int J Pediatr Otorhinolaryngol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea.
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