Protection against ischemic cochlear damage by intratympanic administration of AM-111.

Abstract

OBJECTIVE:

AM-111, a cell-permeable peptide inhibitor of c-Jun N-terminal kinase, was investigated for its protective effects against ischemic damage of the cochlea in gerbils.

METHODS:

Transient cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for l5 minutes. Then, 10 μl of AM-111 at a concentration of l, 10, or 100 μM in hyaluronic acid gel formulation was applied onto the round window 30 minutes after the insult. Gel without active substance was used in a control group. Treatment effects were evaluated by auditory brainstem response (ABR) and histology of the inner ear.

RESULTS:

In controls, transient cochlear ischemia caused a 25.0 ± 5.0 dB increase in the ABR threshold at 8 kHz and a decrease of 13.3 ± 2.3% in inner hair cells at the basal turn on Day 7. Ischemic damage was mild at 2 and 4 kHz. When the animals were treated with AM-111 at 100 μM, cochlear damage was significantly reduced: the increase in ABR threshold was 3.3 ± 2.4 dB at 8 kHz, and the inner hair cell loss was 3.1 ± 0.6% at the basal turn on Day 7. The effects of AM-111 were concentration dependent: 100 μM was more effective than 1 or 10 μM.

CONCLUSION:

Direct application of AM-111 in gel formulation on the round window was effective in preventing acute hearing loss because of transient cochlear ischemia.

• Authors: Yoshinori Omotehara, Nobuhiro Hakuba, Naohito Hato, Masahiro Okada, Kiyofumi Gyo
• Journal: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology (Otol Neurotol) Vol. 32 Issue 9 Pg. 1422-7 (Dec 2011) ISSN: 1537-4505 [Electronic] United States
• PMID: 22089955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• D-JNKI-1

Topics

• Animals
• Cochlea (blood supply, drug effects, pathology)
• Evoked Potentials, Auditory, Brain Stem (drug effects)
• Gerbillinae
• Hair Cells, Auditory (drug effects, pathology)
• Hearing Loss (etiology, pathology, prevention & control)
• Ischemia (complications, pathology)
• Peptides (administration & dosage, therapeutic use)