Background: Although chemotherapy and radiotherapy are effective in cancer treatment, different adverse effects induced by these therapeutic modalities (such as ototoxicity) restrict their clinical use. Co-treat-ment of melatonin may alleviate the chemotherapy/radiotherapy-induced ototoxicity. Objective: In the present study, the otoprotective potentials of melatonin against the ototoxicity induced by chemotherapy and radiotherapy were reviewed. Methods: According to the PRISMA guideline, a systematic search was carried out to identify all relevant studies on “the role of melatonin against ototoxic damage associated with chemotherapy and radiotherapy” in the different electronic databases up to September 2022. Sixty-seven articles were screened based on a pre-defined set of inclusion and exclusion criteria. Seven eligible studies were finally included in this review. Results: The in vitro findings showed that cisplatin chemotherapy significantly decreased the auditory cell viability compared to the control group; in contrast, the melatonin co-administration increased the cell viability of cisplatin-treated cells. The results obtained from the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests demonstrated a decreased amplitude of DPOAE and increased values of ABR I-IV interval and ABR threshold in mice/rats receiving radiotherapy and cisplatin; nevertheless, mela-tonin co-treatment indicated an opposite pattern on these evaluated parameters. It was also found that cisplatin and radiotherapy could significantly induce the histological and biochemical changes in the auditory cells/tis-sue. However, melatonin co-treatment resulted in alleviating the cisplatin/radiotherapy-induced biochemical and histological changes. Conclusion: According to the findings, it was shown that melatonin co-treatment alleviates the ototoxic damage induced by chemotherapy and radiotherapy. Mechanically, melatonin may exert its otoprotective effects via its anti-oxidant, anti-apoptotic, and anti-inflammatory activities and other mechanisms.
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