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


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.


CONCLUSIONS
The MMP inhibitors oxytetracycline and ilomastat protect from cochlear lateral wall damage caused by LPS-induced labyrinthitis.
Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea.
Cheol Hee
CH
Choi
Chul Ho
CH
Jang
Yong Bum
YB
Cho
Si Young
SY
Jo
Min Young
MY
Kim
Byung Young
BY
Park
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003051:Cochlea / Q000473:pathology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D034381:Hearing Loss / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D006877:Hydroxamic Acids; D007211:Indoles / Q000627:therapeutic use*; D007322:Instillation, Drug; D007762:Labyrinthitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010118:Oxytetracycline / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D006877:Hydroxamic Acids; D007211:Indoles; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; C119203:ilomastat; D010118:Oxytetracycline