ROS Scavenger, Ebselen, Has No Preventive Effect in New Hearing Loss Model Using a Cholesterol-Chelating Agent

Abstract

Background and Objectives The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-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 HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. Materials and Methods Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. Results HPβCD-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 HPβCD-induced hearing loss or alter the resulting histopathology. Conclusions The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.

Estrogen Replacement Reduces Hearing Threshold Shifts and Cochlear Hair Cell Loss After Acoustic Overexposure in Ovariectomized Rats

“…Several previous studies have shown that estrogen is protective against noise exposure and glutamate toxicity [ 16 , 17 ]. Estrogen can increase the production of the powerful antioxidants superoxide dismutase 2 and hydrogen sulfide, conferring protection against oxidative stress and decreasing the production of reactive oxygen species [ 18 , 19 ]. An estrogenstimulated increase in the production of brain-derived neurotrophic factor may also confer protective effects [ 16 ].…”

Enhanced Inner-Ear Organoid Formation from Mouse Embryonic Stem Cells by Photobiomodulation

“…After mounting, the cells were permeabilized with 0.25% Triton X-100 (Sigma-Aldrich) in PBS for 10 min at room temperature (RT) and blocked for 1 h at RT with 10% normal goat serum (NGS; Vector Laboratories, Burlington, ON, Canada) and 0.1% Triton X-100 to prevent nonspecific binding. 45 To identify MYO7A-positive cells inside organoids, cells were incubated with primary antibody in PBS containing 3% NGS and 0.1% Triton X-100 overnight at 4 C. The cells were washed three times with PBS for 5 min each and then incubated with corresponding secondary antibody for 1 h. Nuclei were visualized using 4 0 ,6-diamidino-2-phenylindole (DAPI). The primary antibodies are shown in Table S5.…”

Blood Prestin Levels in Normal Hearing and in Sensorineural Hearing Loss: A Scoping Review

“… Hana and Bawi (2018) observed a significant positive correlation between prestin blood levels and blood 8 OHdg. Nevertheless, evidence from age- and noise-related HL rodent models shows that intracochlear reactive oxidative species accumulation may affect, to some degree, OHCs’ lateral wall and electromotility ( Chen 2006 ; Chen et al 2009 ; Lee et al 2019 ). OHC structure changes may decrease prestin’s cellular, and thus free intracochlear, concentration, which may consequently have an effect on its blood concentration.…”