Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals.
OBJECTIVE
The role of transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) as early indicators of cisplatin-induced ototoxicity in three different rodent species--the guinea pig. the albino rat, and the fat sand rat (Psammomys obesus)--was investigated. In addition, an attempt was made to determine which of the three rodent species is most susceptible to cisplatin-induced ototoxicity as measured by auditory brainstem responses (ABR), BACKGROUND: There have been numerous clinical and experimental reports on cisplatin-induced ototoxicity, but to the authors' best knowledge, there has been no comparative report on the short-term effects of cisplatin on OAE measured with commercially available equipment between different rodent species.


METHODS
Cisplatin was systemically administered as a single high dose (12 mg/kg intraperitoneally) to all three species, and the ototoxic effects were measured before and 3 days after the injection of cisplatin in the same animals, using ABR, TEOAE, and DPOAE.


RESULTS
The ABR thresholds were significantly elevated in the guinea pigs and the albino rats but not in the sand rats. Significant depression of TEOAE energy and DPOAE amplitude occurred only in the guinea pigs. The depression of the DPOAE was greater than that of the TEOAE. The guinea pigs showed the greatest degree of ototoxicity (depression of ABR and OAE).


CONCLUSIONS
Among the three rodent species, the guinea pig has the potential to be used as a sensitive animal model in studies of cisplatin ototoxicity. The study also showed that the recordings of TEOAE and DPOAE, in addition to ABR, are sensitive techniques for the assessment of cisplatin-induced ototoxicity.
Department of Physiology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
R
R
Sockalingam
S
S
Freeman
T L
TL
Cherny
H
H
Sohmer
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001835:Body Weight; D002945:Cisplatin / Q000009:adverse effects*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005849:Gerbillinae; D006168:Guinea Pigs; D006311:Hearing Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D051381:Rats; D012680:Sensitivity and Specificity; D013997:Time Factors
D000970:Antineoplastic Agents; D002945:Cisplatin