Abstract
Cisplatin is used to treat a variety of solid tumors in both children and adults. However, cisplatin has serious side-effects, some of which may permanently affect patients' quality of life following treatment, such as ototoxicity. There is currently no FDA-approved therapy for the prevention or treatment of cisplatin-induced hearing loss. Herein we examine the potential for statins to prevent cisplatin-induced ototoxicity. Statins, a class of drugs commonly used to prevent or manage hypercholesterolemia, have been of clinical utility for decades with dependable outcomes and reliable safety profiles in humans. Statins are known to be protective in animal models of noise-induced and age-related hearing loss. Moreover, studies have demonstrated an additive benefit of statins in cancer treatment. In the current study, lovastatin reduces cisplatin-induced hearing loss in adult mice. Lovastatin-mediated protection was significantly greater among female than male mice, and the dose of lovastatin required for protection was different between the sexes. Taken together our data indicate that lovastatin reduces cisplatin-induced hearing loss in mice and suggest that concurrent statin and cisplatin therapy may represent a feasible clinical strategy for reducing cisplatin-induced ototoxicity that should be explored for future clinical use.