Trimethyltin effects on auditory function and cochlear morphology

Abstract

Trimethyltin (TMT) is a neurotoxicant known to alter auditory function. The present study was designed to compare TMT-induced auditory dysfunction using behavioral, electrophysiological, and anatomical techniques. Adult male Long-Evans hooded rats ( n = 9–12/group) were acutely exposed to saline, 3, 5, or 7 mg/kg TMT. Auditory thresholds were determined 11 weeks postdosing for 5- and 40-kHz tones using reflex modification of the auditory startle response (ASR). Brainstem auditory evoked response (BAER) thresholds were determined for 5-, 40-, and 80-kHz tonal stimuli 9 weeks postdosing. Cochlear histology was assessed at 13 weeks postdosing. Functional endpoints demonstrated a high-frequency hearing loss. ASR thresholds for 40-kHz tones were elevated 25–35 dB in all dosage groups. BAER thresholds for 40- and 80-kHz tones were elevated 30–50 dB in the 5 and 7 mg/kg groups. Organ of Corti surface preparations revealed a pattern of damage suggesting classical ototoxicity. That is, outer hair cells died preferentially in regions associated with high-frequency hearing, in a dosage-dependent manner from base to apex. These data demonstrate the utility of the ASR and BAER in detecting functional alterations in audition and indicate that TMT-induced high-frequency hearing loss is associated with cochlear damage.