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Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of
Cheol Hee Choi1, Chul Ho Jang, Yong Bum Cho
1Research Center for Resistant Cells, Chosun Medical School, Gwangju, South Korea.
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.
Insights
Matrix metalloproteinase (MMP) inhibitors, oxytetracycline and ilomastat, protect against hearing loss and cochlear damage from lipopolysaccharide (LPS)-induced labyrinthitis.
Area of Science:
- Ototoxicology
- Pharmacology
- Cell Biology
Background:
- Matrix metalloproteinases (MMPs) play a role in inflammatory processes.
- Lipopolysaccharide (LPS) can induce labyrinthitis, leading to cochlear damage and hearing loss.
Purpose of the Study:
- To investigate the protective effects of oxytetracycline and ilomastat against LPS-induced cochlear damage.
- To evaluate the impact of these MMP inhibitors on auditory function, cochlear blood flow, and the blood-labyrinth barrier.
Main Methods:
- Experiments were conducted on guinea pigs with induced labyrinthitis via intratympanic LPS instillation.
- Auditory brainstem response (ABR), cochlear blood flow (CBF), and blood-labyrinth barrier (BLB) integrity were measured.
- Organ of Corti was assessed using field emission scanning electron microscopy (FE-SEM), and MMP expression was analyzed by gelatin zymography.
Main Results:
- MMP inhibitors significantly protected against hearing loss and hair cell damage.
- Treatment with oxytetracycline and ilomastat restored cochlear blood flow and reduced blood-labyrinth barrier opening.
- Active MMP-9 expression, elevated in the LPS group, was attenuated by MMP inhibitor treatment.
Conclusions:
- Oxytetracycline and ilomastat demonstrate protective effects against cochlear lateral wall damage.
- MMP inhibition is a potential therapeutic strategy for labyrinthitis and associated hearing impairment.
