Inositol hexaphosphate alleviates ototoxicity and age-related hearing loss by preserving cochlear hair cells in mice

Background and Purpose: Inositol hexaphosphate (IP6) is a natural carbohydrate compound in plants and mammalian cells. We aimed to investigate whether IP6 could protect cochlear hair cells and ameliorate sensorineural hearing loss (SNHL) in multiple experimental mouse models of SNHL. Experimental Approach: Three SNHL female mouse models were designed, namely (1) a model induced by the chemotherapy drug cisplatin (3 mg kg−1, intraperitoneal [i.p.] injection), (2) a model induced by aminoglycosides (kanamycin, 1 g kg−1, subcutaneous injection; furosemide 0.1 g kg−1, i.p. injection), and (3) an age-related hearing loss (ARHL) mouse model. For IP6 treatments, IP6 (40 or 80 mg kg−1) was injected i.p. into multiple mouse models to investigate its protective effects on SNHL and ARHL. In addition, another group of mice was fed 2% IP6 (added in their drinking water) to investigate its protective effects on ARHL. Key Results: The collected ABR data suggested that IP6 (80 mg kg−1) significantly reduced hearing threshold shifts in all three female mouse models. Furthermore, the collected immunohistochemical staining data suggested that IP6 significantly ameliorated the loss of outer hair cells in all three mouse models. Conclusion and Implications: These findings support further investigation of IP6 as a potential otoprotective agent for future clinical translation.