Evaluation of Nivolumab for Ototoxic Effects: An Animal Study in Rats

OBJECTIVES: The aim of this study was to assess whether nivolumab is ototoxic in rats and whether this ototoxicity is dose-dependent.

MATERIALS and METHODS: Twelve rats were divided into two groups: Group 1 (control group, 6 rats, 12 ears) received intraperitoneal saline for 14 days. Group 2 (study group, 6 rats, 12 ears) and received two doses of 3 mg/kg intraperitoneal nivolumab within 14 days. Auditory brainstem responses (ABRs) were performed preoperatively and 4 and 8 weeks postoperatively. We compared between the groups, morphologic appearance of spiral ganglion cells and organ of Corti and density of spiral ganglion cells (measured with conventional light microscope connected to a personal computer).

RESULTS: In our control group, both spiral ganglion and organ of corti had a normal morphological appearance. In our study group, spiral ganglion cells had a normal morphological appearance. However, some sections showed possibly mild degenerative changes in the organ of corti. Of 12 samples in the study group, four had a significant loss of density of spiral ganglion cells compared to the control group. The baseline ABR thresholds did not significantly differ between the groups (p=0.713). There was no statistically significant difference between the groups regarding ABR thresholds at week 4 (p=0.347). However, a statistically significant difference was observed in the ABR thresholds at week 8 (p=0.045).

CONCLUSION: The results of our study showed that nivolumab treatment has ototoxic effects. Based on our results, we recommend monitoring the changes in the hearing ability of chemotherapy patients.

Cite this article as: Güler İ, Kuzucu İ, Baklacı D, Kum RO, Özhamam Uçaryılmaz E, Özcan M. Evaluation of Nivolumab for Ototoxic Effects: An Animal Study in Rats. J Int Adv Otol 2020; 16(2): 218-21.