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Int J Pediatr Otorhinolaryngol. 2014 Mar;78(3):465-70. doi: 10.1016/j.ijporl.2013.12.022. Epub 2013 Dec 27.

ALH-L1005 attenuates endotoxin induced inner ear damage.

Author information

1
Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea; Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea. Electronic address: chulsavio@hanmail.net.
2
Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea.
3
Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea; Department of Bio New Drug Development, Chosun University, Gwangju, South Korea.
4
Department of Bio New Drug Development, Chosun University, Gwangju, South Korea.
5
Department of Biomechanical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Pusan, South Korea.
6
AngioLab, Daejeon, South Korea.

Abstract

OBJECTIVE:

To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS.

MATERIALS AND METHODS:

Tube formation using human umbilical vein endothelial cell (HUVEC) and matrix metalloproteinase (MMP)-9 inhibition assay was performed. 24 guinea pigs were randomly divided into three groups. Intratympanic instillation of LPS (n=8) as negative control, instillation of oxytetracycline 1h after LPS as positive control (n=8), and intratympanic instillation of ALH-L1005 (n=8) 1h after LPS were considered experimental group. Evaluation by auditory brainstem response (ABR) measurement, cochlear blood flow, and blood-labyrinth barrier (BLB) permeability were performed. Cochlear hair cells were observed by field emission-scanning electron microscopy (FE-SEM). MMP-9 activation was measured by gelatin zymography.

RESULTS:

For HUVEC, the tube formation was suppressed in a dose dependant manner. ALH-L1005 inhibited the MMP-9 activity prominently. It also attenuated the elevation of LPS-induced hearing threshold shift and recovery of CBF. By FE-SEM, cochlear hair cells could be preserved in experimental group. ALH-L1005 significantly reduced the BLB opening compared to LPS group. Active MMP-9 expression could be detected in the LPS group. In contrast to ALH-L1005 group, active MMP-9 expression was not detected.

CONCLUSION:

Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.

KEYWORDS:

Damage; Horse chestnut; Inner ear; Lipopolysaccharide

PMID:
24418183
DOI:
10.1016/j.ijporl.2013.12.022
[Indexed for MEDLINE]

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