ALH-L1005 attenuates endotoxin induced inner ear damage

Chul Ho Jang; Yong Beom Cho; Cheol Hee Choi; Yoon Seok Jang; Sook Jin Jang; Won-Kyo Jung; Byung Young Park; Min Young Kim

doi:10.1016/j.ijporl.2013.12.022

ALH-L1005 attenuates endotoxin induced inner ear damage

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

Authors

Chul Ho Jang¹, Yong Beom Cho², Cheol Hee Choi³, Yoon Seok Jang⁴, Sook Jin Jang⁴, Won-Kyo Jung⁵, Byung Young Park⁶, Min Young Kim⁶

Affiliations

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.

PMID: 24418183
DOI: 10.1016/j.ijporl.2013.12.022

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Topical
Aesculus*
Animals
Cochlea / drug effects
Cochlea / pathology*
Disease Models, Animal
Endotoxins / pharmacology
Endotoxins / toxicity
Guinea Pigs
Human Umbilical Vein Endothelial Cells / drug effects
Human Umbilical Vein Endothelial Cells / physiology
Humans
Labyrinthitis / drug therapy*
Labyrinthitis / pathology*
Labyrinthitis / prevention & control
Lipopolysaccharides / pharmacology
Lipopolysaccharides / toxicity
Matrix Metalloproteinase 9 / drug effects
Matrix Metalloproteinase 9 / metabolism*
Microscopy, Electron, Scanning
Plant Preparations / administration & dosage
Random Allocation
Reference Values

Substances

Endotoxins
Lipopolysaccharides
Plant Preparations
Matrix Metalloproteinase 9