Ebselen attenuates tobramycin-induced ototoxicity in mice.

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
Rende GuJonathan Kil

Abstract

Cystic fibrosis patients are often adminstered tobramycin to treat pulmonary infections. Unfortunately, a common side effect is hearing loss, which can fluctuate. Ebselen has known anti-inflammatory properties and could reduce the incidence and severity of tobramycin-induced hearing loss. In vitro: neonatal cochlear cultures were treated with tobramycin or cotreated with tobramycin and ebselen for 3 days. In vivo: adult mice were injected with tobramycin or tobramycin and ebselen for 14 days. ABRs were collected in a repeated measures design until 56 days after treatments. ABR threshold shifts were analyzed and a novel cochleotoxic criteria applied to determine the incidence of ototoxicity. Cochlear immunohistology was analyzed for IHC and OHC loss. Tobramycin leads to significant IHC and OHC loss in cochlear explant cultures. Ebselen co-treatment at 1:20 concentrations resulted in significant otoprotection. Tobramycin leads to significant ABR threshold shifts that are ameliorated by ebselen co-treatment. Hearing loss did not correlate with significant IHC or OHC loss. This mouse model of tobramycin-induced ototoxicity is clinically relevant in that it results in an incidence and severity of hearing loss recently documented in ...Continue Reading

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Citations

Oct 13, 2020·Frontiers in Neuroscience·Ryan J LongeneckerJonathan Kil
Mar 9, 2021·Hearing Research·Jonathan KilRyan J Longenecker
Apr 30, 2021·Frontiers in Pharmacology·Dafei LiGuangyong Tian
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Claudio SantiLuca Sancineto

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