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Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model

Objective Programmed cell death protein-1 (PD-1) inhibitors that have been recently introduced for the systemic treatment of head and neck cancers offer the advantage of fewer side effects and more effective treatment than chemotherapy drugs. A review of the literature shows that the ototoxic side e...

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Autores principales: Kuzucu, İhsan, Baklacı, Deniz, Guler, İsmail, Uçaryılmaz, Esra Özhamam, Kum, Rauf Oğuzhan, Özcan, Müge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cureus 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890160/
https://www.ncbi.nlm.nih.gov/pubmed/31827988
http://dx.doi.org/10.7759/cureus.6057
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author Kuzucu, İhsan
Baklacı, Deniz
Guler, İsmail
Uçaryılmaz, Esra Özhamam
Kum, Rauf Oğuzhan
Özcan, Müge
author_facet Kuzucu, İhsan
Baklacı, Deniz
Guler, İsmail
Uçaryılmaz, Esra Özhamam
Kum, Rauf Oğuzhan
Özcan, Müge
author_sort Kuzucu, İhsan
collection PubMed
description Objective Programmed cell death protein-1 (PD-1) inhibitors that have been recently introduced for the systemic treatment of head and neck cancers offer the advantage of fewer side effects and more effective treatment than chemotherapy drugs. A review of the literature shows that the ototoxic side effects of the PD-1 inhibitor have not yet been fully elucidated. In this study, we aimed to investigate whether the PD-1 inhibitor has ototoxic activity using both electrophysiological and histopathological methods. Methods A total of 24 rats, 12 for the study group, and 12 for the control group were included in the study. The study group was administered the PD-1 inhibitor. The auditory brainstem responses (ABR) of the study and control groups were evaluated. At the end of the study, all animals were sacrificed, and their cochleae were examined by immunohistochemical staining. Results In the study group, the ABR values ​​were 13.95 ± 2.70 before treatment, 15.83 ± 1.94 at week 4 of treatment (p=0.024), and 15.00 ± 1.06 at week 7 (p=0.157). Furthermore, according to immunohistochemical staining, the cochlear hair cells were reduced in the study group compared to the control group. Conclusion It was determined that the PD-1 inhibitor showed ototoxic activity during the course of treatment, but this was spontaneously resolved during follow-up. The clinical significance of these findings should be supported by human studies.
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spelling pubmed-68901602019-12-11 Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model Kuzucu, İhsan Baklacı, Deniz Guler, İsmail Uçaryılmaz, Esra Özhamam Kum, Rauf Oğuzhan Özcan, Müge Cureus Otolaryngology Objective Programmed cell death protein-1 (PD-1) inhibitors that have been recently introduced for the systemic treatment of head and neck cancers offer the advantage of fewer side effects and more effective treatment than chemotherapy drugs. A review of the literature shows that the ototoxic side effects of the PD-1 inhibitor have not yet been fully elucidated. In this study, we aimed to investigate whether the PD-1 inhibitor has ototoxic activity using both electrophysiological and histopathological methods. Methods A total of 24 rats, 12 for the study group, and 12 for the control group were included in the study. The study group was administered the PD-1 inhibitor. The auditory brainstem responses (ABR) of the study and control groups were evaluated. At the end of the study, all animals were sacrificed, and their cochleae were examined by immunohistochemical staining. Results In the study group, the ABR values ​​were 13.95 ± 2.70 before treatment, 15.83 ± 1.94 at week 4 of treatment (p=0.024), and 15.00 ± 1.06 at week 7 (p=0.157). Furthermore, according to immunohistochemical staining, the cochlear hair cells were reduced in the study group compared to the control group. Conclusion It was determined that the PD-1 inhibitor showed ototoxic activity during the course of treatment, but this was spontaneously resolved during follow-up. The clinical significance of these findings should be supported by human studies. Cureus 2019-11-02 /pmc/articles/PMC6890160/ /pubmed/31827988 http://dx.doi.org/10.7759/cureus.6057 Text en Copyright © 2019, Kuzucu et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Otolaryngology
Kuzucu, İhsan
Baklacı, Deniz
Guler, İsmail
Uçaryılmaz, Esra Özhamam
Kum, Rauf Oğuzhan
Özcan, Müge
Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model
title Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model
title_full Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model
title_fullStr Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model
title_full_unstemmed Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model
title_short Investigation of the Ototoxic Effect of Pembrolizumab Using a Rat Model
title_sort investigation of the ototoxic effect of pembrolizumab using a rat model
topic Otolaryngology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890160/
https://www.ncbi.nlm.nih.gov/pubmed/31827988
http://dx.doi.org/10.7759/cureus.6057
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