title: ALH-L1005 attenuates endotoxin induced inner ear damage.
abstract: OBJECTIVE
  To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS.
  
  
  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.
  
  
  CONCLUSIONS
  Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.
authors.affiliation: 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.
authors.forename: Chul Ho
authors.initials: CH
authors.lastname: Jang
authors.affiliation: Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Cho
authors.affiliation: Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea; Department of Bio New Drug Development, Chosun University, Gwangju, South Korea.
authors.forename: Cheol Hee
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Department of Bio New Drug Development, Chosun University, Gwangju, South Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Jang
authors.affiliation: Department of Bio New Drug Development, Chosun University, Gwangju, South Korea.
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Department of Biomechanical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Pusan, South Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.affiliation: AngioLab, Daejeon, South Korea.
authors.forename: Byung Young
authors.initials: BY
authors.lastname: Park
authors.affiliation: AngioLab, Daejeon, South Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
mesh_terms: D000287:Administration, Topical; D031319:Aesculus; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology / Q000633:toxicity; D006168:Guinea Pigs; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007762:Labyrinthitis / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D028321:Plant Preparations / Q000008:administration & dosage; D011897:Random Allocation; D012016:Reference Values
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D028321:Plant Preparations; D020780:Matrix Metalloproteinase 9
keywords: Damage; Horse chestnut; Inner ear; Lipopolysaccharide