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There are temporal changes in the outer-hair-cell-specific protein, prestin, in the blood after administration of low-dose cisplatin.Two rodent models of ototoxicity were used. After control and baseline data collection, mice (n = 30) and guinea pigs (n = 10), respectively, were treated with cisplatin at 8 mg/kg. Auditory brainstem responses were recorded on Days 1, 3, 7, and 14 after treatment. Five mice were sacrificed at each time point and serum samples were obtained. A group of 10 guinea pigs were tested and serum samples were collected at each time point. Serum prestin concentrations were measured using separate enzyme-linked immunosorbent assays for each species.Auditory brainstem responses thresholds changed relatively little in mice, but gradually increased in guinea pigs, as a function of time after cisplatin exposure. In contrast, serum prestin concentrations rose, reaching a peak on Days 3 and 7 after cisplatin treatment in mouse and guinea pig, respectively, before declining back to or below baseline/control levels 14 days after treatment.There was a time-dependent pattern of change in serum prestin after exposure to low-dose cisplatin in a resistant (mouse) and sensitive (guinea pig) rodent models. These comparative results suggest prestin may serve as a biomarker for cisplatin ototoxicity.