Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of endotoxin

• Published in: International journal of pediatric otorhinolaryngology Vol. 76; no. 4; pp. 544 - 548
• Main Authors: Choi, Cheol Hee, Jang, Chul Ho, Cho, Yong Bum, Jo, Si Young, Kim, Min Young, Park, Byung Young
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.04.2012
• Subjects: Animals; Anti-Bacterial Agents - therapeutic use; Brain stem; Cerebral blood flow; Cochlea; Cochlea - pathology; Disease Models, Animal; Ear; Endotoxins; Evoked Potentials, Auditory, Brain Stem; Extravasation; Gelatin; Gelatinase A; Gelatinase B; Guinea Pigs; Hair cells; Hearing loss; Hearing Loss - etiology; Hearing Loss - pathology; Hearing Loss - prevention & control; Hydroxamic Acids; Indoles - therapeutic use; Inhibitor; Instillation, Drug; Labyrinthitis; Labyrinthitis - etiology; Labyrinthitis - pathology; Labyrinthitis - prevention & control; Lateral wall; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Male; Matrix metalloproteinase; Matrix Metalloproteinase Inhibitors; Organ of Corti; Otitis interna; Otolaryngology; Oxytetracycline; Oxytetracycline - therapeutic use; Pediatrics; Scanning electron microscopy; Statistical analysis; Cochlea; Inhibitor; Labyrinthitis; Matrix metalloproteinase; Lateral wall
• ISSN: 0165-5876; 1872-8464
• DOI: 10.1016/j.ijporl.2012.01.013

Abstract 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.