Long-Term Synergistic Interaction of Cisplatin- and Noise-Induced Hearing Losses

Objective: Past experiments in the literature have shown that cisplatin interacts synergistically with noise to create hearing loss. Much of the previous work on the synergistic interaction of noise and cisplatin tested exposures that occurred very close together in time. The present study assessed whether rats that have been exposed to cisplatin continue to show increased susceptibility to noise-induced hearing loss months after conclusion of the cisplatin exposure. Design: Thirty-two Fischer 344/NHsd rats were exposed to one of five conditions: (1) cisplatin exposure followed by immediate cochlear tissue harvest, (2) cisplatin exposure and a 20-week monitoring period before tissue harvest, (3) cisplatin exposure followed immediately by noise exposure, (4) cisplatin exposure followed by noise exposure 16 weeks later, and (5) noise exposure without cisplatin exposure. The cisplatin exposure was an 8-week interval in which cisplatin was given every 2 weeks. Cochlear injury was evaluated using auditory brainstem response thresholds, P1 wave amplitudes, and postmortem outer hair cell counts. Results: The 8-week cisplatin exposure induced little threshold shift or P1 amplitude loss, and a small lesion of missing outer hair cells in the basal half of the cochlea. The rats exposed to noise immediately after the cisplatin exposure interval showed a synergistic interaction of cisplatin and noise. The group exposed to noise 16 weeks after the cisplatin exposure interval also showed more severe threshold shift and outer hair cell loss than control subjects. The controls exposed to cisplatin and monitored for 20 weeks showed little threshold shift or outer hair cell loss, but did show P1 wave amplitude changes over the 20-week monitoring period. Conclusions: The results from the groups exposed to cisplatin followed by noise, combined with the findings from the cisplatin- and noise-only groups, suggest that the cisplatin induced cochlear injuries that were not severe enough to result in threshold shift, but left the cochlea in a state of heightened susceptibility to future injury. The heightened susceptibility to noise injury was still present 16 weeks after the conclusion of the cisplatin exposure.

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