On a model of cisplatin-induced ototoxicity in Wistar rats

An experimental in vivo model of cisplatin-induced ototoxicity (CO) is a prerequisite for developing methods to prevent hearing loss resulting from cisplatin (CP) chemotherapy. However, there are no clear guidelines regarding its design in a research model as widely used as the Wistar rat. Objective. To develop and validate a model of auditory analyzer injury in Wistar rats that reflects the specific nature of cisplatin-induced ototoxicity. Material and methods. The study was conducted on male Wistar rats of SPF status, n=24, weighing 300–340 g. CP was administered in doses of 6, 8, 10, and 12 mg/kg as a single intraperitoneal injection to four groups of 6 rats (12 ears). Survival, body weight and audiological parameters were assessed. Otoacoustic emissions at the distortion product frequency (DP OAE) and auditory brainstem responses (ABR) were examined at baseline and on day 30 of the experiment. The amplitude of DP OAE was assessed at 8 and 10 kHz; ABR was assessed during monaural stimulation with 20 and 30 kHz tones in a free sound field. Additionally, plasma creatinine levels and histological preparations of cochleae and kidneys were assessed. Results. A single administration of CP at a dose of 8 mg/kg or higher in Wistar rats is associated with acute mortality. A CIOT model allowing for animal survival is achieved using CP at a dose of 6 mg/kg. In this case, by the end of the experiment, a decrease in the amplitude of the OAE in the 10 kHz range was noted (p=0.043); for the ABR, an increase in the threshold by 10–15 dB in response to a 20 kHz stimulus was observed in 3 out of 12 ears, along with a decrease in the amplitude of the second peak (p=0.012). Histological sections of the temporal bones revealed partial neuronal death in the spiral ganglion of the cochlea’s main turn. Kidney tissue showed irreversible damage characteristic of tubulo-interstitial nephritis. However, plasma creatinine levels remained within the reference range. Conclusion. A single intraperitoneal administration of CP at a dose of 6 mg/kg allows the establishment of a model of acute CO in adult Wistar rats, characterized by moderate depression of audiological parameters and irreversible pathomorphological changes in the neurons of the spiral ganglion. The absence of mortality and biochemical signs of nephrotoxicity indicates specific damage to the peripheral component of the auditory system without the additional ototoxic influence of renal failure factors.