The protective efficacy of rosmarinic acid in radiotherapy-induced ototoxicity

Background: Radiotherapy-induced ototoxicity remains a significant clinical problem, and potential protective agents such as rosmarinic acid have gained increasing research interest. Objectives: This study investigated the effectiveness of systemic and local rosmarinic acid administration in radiotherapy-induced ototoxicity using the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE) test, and histopathological methods. Material and methods: Sixty rats were included in the study. Seven groups were created, including control, radiotherapy-only, and combinations of radiotherapy with intratympanic or intraperitoneal rosmarinic acid, as well as a radiotherapy plus intratympanic saline group. ABR and DPOAE measurements were performed with all animals initially and at the end of the third week. The temporal bones of the decapitated rats were also fixed in formalin for histopathological measurements. Results: ABR thresholds increased significantly in the radiotherapy–only group (from 22.8 ± 3.1 to 45.4 ± 3.6 dB, p = 0.004) and the radiotherapy plus intratympanic saline group (from 24.6 ± 3.1 to 47.1 ± 3.6 dB, p = 0.005), while remaining stable in the other groups (p > 0.05). Correspondingly, DPOAE values decreased and histopathological damage scores were markedly higher in these two groups. Conclusions and significance: Rosmarinic acid protects against radiotherapy-induced ototoxicity when applied both systemically and locally, as confirmed by histopathological examination and objective audiological methods. © 2026 Acta Oto-Laryngologica AB (Ltd).