ALH-L1005 attenuates endotoxin induced inner ear damage

ObjectiveTo assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS.Materials and methodsTube 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 1 h after LPS as positive control (n = 8), and intratympanic instillation of ALH-L1005 (n = 8) 1 h 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.ResultsFor 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.ConclusionOur results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.