title: Noise trauma and systemic application of the selective glucocorticoid receptor modulator compound A.
abstract: BACKGROUND
  Selective glucocorticoid receptor modulators (SEGRMs) comprise a novel class of drugs promising both reduced side effects and similar pharmacological potency relative to glucocorticoids, which presently serve as the only clinical treatment for many otologic disorders. In the first otologic SEGRM experiment in an animal model of noise trauma, we compare the effects of Compound A (a SEGRM) and dexamethasone (potent glucocorticoid).
  
  
  METHODS
  Forty adult guinea pigs received experimental treatment once daily for ten days. The animals were divided into four cohorts based on the treatment received: Compound A (1 mg/kg or 3 mg/kg), dexamethasone (1 mg/kg) as gold standard, or water as negative control. After five applications, animals were exposed to broadband noise (8-16 kHz) at 115 dB for three hours. Hearing thresholds were determined by recording auditory brainstem responses to clicks and noise bursts (1-32 kHz) and were assessed a week prior to and immediately after exposure, as well as on days 1, 3, 7, 14, 21, and 28. Cochleae were prepared as whole-mounts or embedded and sectioned for histological analysis.
  
  
  RESULTS
  Relative to the control treatments, Compound A failed to preserve auditory thresholds post-noise exposure with statistical significance. Histological analyses confirm the physiological result.
  
  
  CONCLUSIONS
  The present findings suggest that Compound A does not have substantial otoprotective capacities in a noise trauma model.
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Lukas D
authors.initials: LD
authors.lastname: Landegger
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. clemens.honeder@meduniwien.ac.at.
authors.forename: Clemens
authors.initials: C
authors.lastname: Honeder
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Chengjing
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Pathobiology, Institute of Anatomy, Histology and Embryology, University of Veterinary Medicine, Veterinaerplatz 1, 1210, Vienna, Austria.
authors.forename: Hanna
authors.initials: H
authors.lastname: Schöpper
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Engleder
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gstoettner
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Arnoldner
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage*; D006168:Guinea Pigs; D009622:Noise / Q000009:adverse effects*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*
chemical_list: D011965:Receptors, Glucocorticoid; D003907:Dexamethasone
keywords: Compound A; Dexamethasone; Guinea pigs; Noise-induced hearing loss; Otoprotection; SEGRMs; Selective glucocorticoid receptor modulators