title: Electrophysiological findings in the Sprague-Dawley rat induced by moderate-dose carboplatin.
abstract: Carboplatin is a second generation platinum-containing anti-tumor drug which selectively alters the micromechanical function of the inner hair cells (IHCs) of the organ of Corti in the chinchilla. Data from a recent study [Wake et al., Acta Otolaryngol. 116 (1996) 374-381], using the chinchilla model, have suggested that a moderate dose of carboplatin alters the efferent feedback loop gain of the OHCs. The present study was designed to evaluate the possible 'efferent feedback alteration mechanism' in the Sprague-Dawley rat using distortion product otoacoustic emissions (DPOAEs). A moderate dose of carboplatin (50 mg/kg body weight) was administered by a 30 min i.p. infusion. Pre- and 72-h post-treatment DPOAE and auditory brainstem response (ABR) recordings were acquired from a group of 12 rats. The animals were anesthetized with a ketamine-atropin anesthesia administered in two consecutive phases. The DPOAE responses (cubic distortion products) were recorded with four asymmetrical protocols: P1=60-50, P2=50-40, P3=40-30 and P4=30-20 dB SPL (sound pressure level), in the frequency range from 4.0 to 16 kHz. ABR responses were obtained for bipolar clicks and tone pips at the frequencies 8.0, 10.0, 20.0 and 30 kHz using stimuli in the range from 100 to 30 dB SPL. Significant ABR threshold shifts of 15 dB were observed at 30 kHz, and shifts of 10 dB at 20, 16 and 10 kHz. The comparison of pre- and post-treatment DPOAE responses did not reveal any significant changes for protocols P1, P2 and P4. Data from the P3 protocol indicated a decrease of the DPOAE amplitude. The findings from the rat model suggest that (a) moderate doses of carboplatin do not affect the efferent feedback loop OHC function and (b) the cochlear susceptibility to carboplatin across species is different, even at moderate-dose regimes.
authors.affiliation: Department of Audiology, University of Ferrara, 203 Corso Giovecca, 44100 Ferrara, Italy. sdh@dns.unife.it
authors.forename: Stavros
authors.initials: S
authors.lastname: Hatzopoulos
authors.forename: Joseph
authors.initials: J
authors.lastname: Petruccelli
authors.forename: Goran
authors.initials: G
authors.lastname: Laurell
authors.forename: Maurizio
authors.initials: M
authors.lastname: Previati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001696:Biomechanical Phenomena; D016190:Carboplatin / Q000633:toxicity*; D002682:Chinchilla; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D016057:Evoked Potentials, Auditory, Brain Stem; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D017084:Otoacoustic Emissions, Spontaneous; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin