A clinically derived guinea pig dosing model of cisplatin ototoxicity

James K Stanford; Nicholas A Bosworth; Drew S Morgan; Tianwen Chen; Christopher Spankovich

doi:10.1016/j.heares.2021.108202

A clinically derived guinea pig dosing model of cisplatin ototoxicity

Hear Res. 2021 May:404:108202. doi: 10.1016/j.heares.2021.108202. Epub 2021 Feb 12.

Authors

James K Stanford¹, Nicholas A Bosworth², Drew S Morgan³, Tianwen Chen⁴, Christopher Spankovich⁵

Affiliations

¹ Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: jstanford@umc.edu.
² Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; School of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: nbosworth@umc.edu.
³ Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; School of Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: dsmorgan@umc.edu.
⁴ Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: tchen2@umc.edu.
⁵ Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: cspankovich@umc.edu.

PMID: 33621791
DOI: 10.1016/j.heares.2021.108202

Abstract

The guinea pig is a commonly-used animal model in hearing research, as their audible frequency range is similar to that of humans, and they possess comparatively large cochleae among rodents. Numerous studies have investigated the ototoxic effects of cisplatin in guinea pigs, but these have been mostly limited to single high-dose bolus injections of cisplatin. This method of drug administration is not consistent with human treatment schedules, and therefore lacks translational value to clinical applications. We tested several different cisplatin dosing schedules in guinea pigs based on common research based and clinical regimens, measuring the resulting hearing loss and morbidity (weight loss). We propose a dosing paradigm of once-weekly 4 mg/kg cisplatin injections for three weeks to best mimic clinical treatment schedules. This method resulted in a configuration of hearing loss similar to what is observed in humans along with minimal changes in weight.

Keywords: Auditory brainstem response (ABR); Cisplatin; Guinea pig; Ototoxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / toxicity
Cisplatin / toxicity
Evoked Potentials, Auditory, Brain Stem / drug effects
Guinea Pigs
Hearing
Hearing Loss* / chemically induced
Ototoxicity*

Substances

Antineoplastic Agents
Cisplatin