SOC-V-10 Hearing loss: side-effects of multiple compounds and formulations which can be monitored with functional and histological read-outs

ABSTRACT

Purpose: Hearing loss is a major global health issue affecting around 1.5 billion people worldwide, with an increasing prevalence. Acquired hearing loss is attributed to different environmental factors including ageing, noise exposure, and the intake of ototoxic medicines. Some commonly used medications can considerably affect the auditory system, resulting in cochlear and central damage that can lead to permanent hearing loss. More than 600 classes of medications are ototoxic. The most used in clinical practice are chemotherapeutics (cisplatin) and aminoglycoside antibiotics (such as gentamicin). Some investigated drugs for Covid-19 treatment (hydroxychloroquine, HCQ) and certain drug delivery agents like cyclodextrins (CD) have also been reported to induce auditory side effects. The aim of these in vivo studies was to provide functional and histological data on auditory assessments related to cisplatin, gentamicin, HCQ, and CD, when administered similarly to clinical protocol. Method(s) The studies were conducted in Wistar rats and Albino guinea pigs * Cisplatin was administered by intraperitoneal route at 10 mg/kg in rats * Gentamicin was administered by intramuscular route at 160 mg/kg for 5 days in rats * HCQ was administered at 62 mg/kg per os daily for five days in rats * A cyclodextrin-based formulation was administered by transtym-panic route at 4 mg/mL 1 h and 30 h after noise exposure in guinea pigs Hearing was assessed using the techniques of Distortion Product Otoacoustic Emissions (DPOAE) and Auditory Brainstem Responses (ABR) at several timepoints. DPOAE are acoustic signals created and amplified by the cochlear epithelium and measured in the ear canal. DPOAE reflect the activity of outer hair cells (OHC). ABR is an electrophysiological measure of the sensorineural activity of the auditory pathway from the cochlea to the central auditory structures in response to a sound stimulus, recorded as electric potentials from scalp electrodes. A cochleogram, an FDA-recommended histological analysis for hair cell counting, was performed at the end of certain studies. Result(s) Results based on ABR thresholds, DPOAE amplitudes, and the cochleogram, showed different patterns of auditory side-effects. Cisplatin induced immediate and permanent hearing loss;gentamicin displayed delayed side-effects on auditory measures;HCQ did not affect Outer Hair Cells but might have had an effect on neurons. CD had an immediate and prolonged effect on hearing. Conclusion(s) This short presentation will help you learn the current available methods to measure hearing in preclinical in-vivo trials using two complementary functional read-outs and a histological analysis, and to determine the different sites of damage. Copyright © 2022 Elsevier B.V.