PROTECTION OF BOTH AUDITORY HAIR-CELLS AND AUDITORY NEURONS FROM CISPLATIN-INDUCED DAMAGE

Cisplatin is an effective anti-neoplastic agent used in the treatment of squamous cell cancer of the head and neck, but with serious side ef fects. One serious side effect is damage to both the auditory hair cel ls and the auditory neurons. The damage to the neurons has been shown to be a direct effect and not due to the loss of the neurotrophic supp ort provided by the hair cells. Several neurotrophins have been shown to lessen the extent of cisplatin induced damage of auditory neurons i n vitro, but these neurotrophins have had no effect on the extent of d amage to the hair cells. D-methionine (D-met) has been demonstrated to provide protection against cisplatin's nephrotoxicity in vivo and oto toxicity in vitro. In this study the combination of brain derived neur otrophic factor (BDNF) with D-met has shown that both auditory neurons and auditory hair cells can be protected from cisplatin induced damag e in vitro. These results demonstrate that this type of combination th erapy (i.e. a neurotrophin combined with a free radical scavenger) can provide more complete protection for the auditory receptor against ci splatin toxicity than either of these agents alone. Because both BDNF and D-met have been shown to have trophic activity in vitro we propose d that the combination of these agents will also provide effective pro tection against cisplatin induced ototoxicity and neurotoxicity of the auditory receptor in vivo.