Establishment of an optimized guinea pig model of cisplatin-induced ototoxicity

Navid Ahmadi; Nodir Saidov; Julia Clara Gausterer; Anne-Margarethe Kramer; Clemens Honeder; Christoph Arnoldner

doi:10.3389/fvets.2023.1112857

Establishment of an optimized guinea pig model of cisplatin-induced ototoxicity

Front Vet Sci. 2023 Apr 13:10:1112857. doi: 10.3389/fvets.2023.1112857. eCollection 2023.

Authors

Navid Ahmadi¹, Nodir Saidov¹, Julia Clara Gausterer², Anne-Margarethe Kramer³, Clemens Honeder¹, Christoph Arnoldner¹

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
² Division of Pharmaceutical Technology and Biopharmaceutics, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.
³ Department of Biomedical Research, Medical University of Vienna, Vienna, Austria.

Abstract

Background: Cisplatin is among the most effective antineoplastic agents and has revolutionized the treatment of many cancer diseases. However, one of its serious side effects is a progressive and irreversible hearing loss, occurring in both adults and children. For the development of otoprotective therapies that prevent this side effect, cisplatin-induced hearing loss animal models are indispensable. Due to the high toxicity of cisplatin, the establishment of such animal models is a difficult and time-consuming task. Here we introduce the detailed protocol of a sophisticated guinea pig model with a sufficient and permanent hearing loss induced by cisplatin. This manuscript is intended to provide guidance in the development of future cisplatin guinea pig models which may reduce the mortality rate of the animals and help to gain more reproducible results.

Methods: Pigmented and unpigmented guineapigs were treated with an intravenous single application of 8 mg/kg cisplatin under general anesthesia. An extensive and long-term intensive care protocol consisting of scheduled application of fluids, antiemetics, analgesics, glucose and supportive feeding among others, was used to ensure wellbeing of the animals. Hearing tests were performed prior to and 5 days after cisplatin application. Animals were then euthanized.

Results: The ABR audiometry 5 days after cisplatin application revealed a hearing threshold ranging from 70 dB to 90 dB in the frequencies from 1 kHz to 32 kHz respectively.All animals presented a good health condition despite the treatment with cisplatin.

Discussion: The introduced care protocol in this manuscript is intended to serve as a guidance for the establishment of a stable guinea pig model for short- and long-term investigation regarding the inner ear and its protection in the frame work of cisplatin-induced damage.

Keywords: cisplatin; guinea pig model; otoprotection; ototoxicity; protocol.

Grants and funding

The authors declare that this study received funding from MED-EL Corporation. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.