Running head: EFFECTS OF COCHLEAR PRE-CONDITIONING ON CISPLATIN OTOXICITY 1 Effects of cochlear pre-conditioning on cisplatin ototoxicity Honors Research Thesis Presented in Partial Fulfillment of the Requirements for graduation with Honors Research

The protective effects of cochlear pre-conditioning have been documented, especially in regard to noise. Conditioning with moderate-intensity noise toughens the ear and makes it more resistant to damage from high-level noise exposures. The goal of the project was to determine whether cochlear pre-conditioning is effective in protecting against the ototoxic effects of cisplatin. Pre-conditioning with noise has shown to reduce hearing loss from cisplatin, but preconditioning with cisplatin had never been attempted. 21 Fischer 344 rats, split into control and experimental groups, were used for the test. Saline solution was administered to the control group while cisplatin was given to the experimental group, each increasing doses throughout the conditioning period. Injections were given once every two weeks with a hearing test during off weeks. The threshold of each animal was determined through measuring auditory brainstem responses while the animal was under sedation. After conditioning, each animal was given a large dose of cisplatin (12 mg/kg) and given a hearing test three days later to determine if the pre-conditioning was successful in reducing hearing loss. During the conditioning phase, animals treated with low-dose cisplatin lost weight in the week after the cisplatin exposure, but did not develop any hearing loss. Following the high dose of cisplatin, results showed that the cochlear pre-conditioning with cisplatin did not reduce cisplatin-induced hearing loss. The experimental group had higher thresholds and was in worse health after the final cisplatin dose than the animals conditioned with saline. Since there was no evidence that the saline conditioning affected cisplatin ototoxicity, the conclusion can be made that prolonged exposure to cisplatin, even at lower exposure levels, weakens the animal and exacerbates cisplatin’s ototoxicity. Therefore, cochlear pre-conditioning prior to cisplatin exposure cannot be executed using cisplatin itself as the conditioning agent. EFFECTS OF COCHLEAR PRE-CONDITIONING ON CISPLATIN OTOXICITY 3