Noise trauma and systemic application of the selective glucocorticoid receptor modulator compound A

Abstract

BackgroundSelective 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).MethodsForty 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.ResultsRelative to the control treatments, Compound A failed to preserve auditory thresholds post-noise exposure with statistical significance. Histological analyses confirm the physiological result.ConclusionThe present findings suggest that Compound A does not have substantial otoprotective capacities in a noise trauma model.

Assessment of the efficacy of a local steroid rescue treatment administered 2 days after a moderate noise-induced trauma in guinea pig

“…Albino guinea pigs usually have lower hearing than pigmented guinea pigs, especially in the midfrequencies [10]. Thus, the albino model might experience poorer recovery probably related to the properties of the stria vascularis which lacked melanin and showed a different glutathione distribution [10,11]; however, this point remains under debate because similar noise trauma experiments performed in both models showed higher hearing loss in pigmented guinea pigs (Table 1) [11][12][13][14].…”

Evaluation of Sustained-Release Steroid Hydrogels in a Guinea Pig Model for Noise-Induced Hearing Loss

“…Organ of Corti whole mounts were prepared as previously described Landegger et al, 2016] and stained with phalloidin-tetramethylrhodamine B isothiocyanate (0.4 µg/ mL in PBS; phalloidin-TRITC; Sigma-Aldrich, Austria) and Hoechst 33342 trihydrochloride trihydrate (5 µg /mL in PBS; Molecular Probes ® , Invitrogen Corp., CA, USA) for 30 min at room temperature. Then samples were embedded in FluorSave TM reagent (Calbiochem, Germany) and analyzed by fluorescence microscopy (Axio Observer Z1 and AxioVision software, Zeiss, Germany).…”