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Evaluation of the selective glucocorticoid receptor agonist compound A for ototoxic effects
Author(s) -
Honeder Clemens,
Engleder Elisabeth,
Schöpper Hanna,
Krause Markus,
Landegger Lukas David,
Plasenzotti Roberto,
Gabor Franz,
Gstoettner Wolfgang,
Arnoldner Christoph
Publication year - 2015
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.25011
Subject(s) - auditory brainstem response , spiral ganglion , medicine , agonist , hearing loss , inner ear , ototoxicity , pharmacology , receptor , audiology , anatomy , chemotherapy , cisplatin
Objectives/Hypothesis To evaluate the selective glucocorticoid receptor agonist (SEGRA) compound A, a potential novel therapeutic for inner ear disorders, for ototoxic effects. Study Design Laboratory animal study. Methods Experimental guinea pigs were grouped as follows: Systemic application of compound A (1.5 mg/kg and 4.5 mg/kg; n = 6/group) and intratympanic application of compound A (1 mM and 10 mM; n = 6/group). Contralateral ears in topically treated animals served as controls. Hearing thresholds were determined by auditory brainstem response before and directly after the application of compound A, as well as on days 3, 7, 14, 21, and 28. At the end of the experiments, temporal bones were harvested for histological evaluation. Results Systemic administration of compound A (1.5 mg/kg and 4.5 mg/kg) did not cause hearing threshold shifts, whereas the intratympanic injection (1 mM and 10 mM) resulted in a hearing loss. Histological analysis of the middle and inner ears after topical compound A application showed alterations in the tympanic membranes, the auditory ossicles, and the round window membranes, whereas spiral ganglion cells and hair cells were not affected. Conclusion SEGRAs such as compound A could provide novel therapeutic options for the treatment of inner ear disorders and reduce metabolic side effects. Whereas the intratympanic application of compound A resulted in a hearing loss, the systemic application of compound A merits evaluation for otoprotective effects in trauma models. Level of Evidence N/A. Laryngoscope , 125:E149–E155, 2015