KMID : 1039520190230020069
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Journal of Audiology & Otology 2019 Volume.23 No. 2 p.69 ~ p.75
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ROS Scavenger, Ebselen, Has No Preventive Effect in New Hearing Loss Model Using a Cholesterol-Chelating Agent
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Lee Min-Young
Kabara Lisa L. Swiderski Donald L. Raphael Yehoash Duncan R. Keith Kim Young-Ho
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Abstract
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Background and Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-¥â-cyclodextrin (HP¥âCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HP¥âCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HP¥âCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HP¥âCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HP¥âCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HP¥âCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HP¥âCD.
Materials and Methods: Ebselen was applied prior to administration of HP¥âCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined.
Results: HP¥âCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HP¥âCD-induced hearing loss or alter the resulting histopathology.
Conclusions: The results indirectly suggest that cochlear damage by HP¥âCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HP¥âCD otopathology is necessary.
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KEYWORD
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Cyclodextrin, Ebselen, Prestin, Tight junctions, Outer hair cell
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