Partial recovery of cisplatin-induced hearing loss in the albino guinea pig in relation to cisplatin dose.
The objective of the present study was to further characterize cochlear recovery after cisplatin damage. We equipped albino guinea pigs with permanent round window electrodes. Cisplatin was injected i.p. on a daily basis at either 1.5 or 2.0 mg/kg/day. Treatment was stopped when the criterion of > or =40 dB loss in the compound action potential iso-response level at 8 kHz had occurred. Either shortly (1-3 days) or long (4 weeks or more) after this stop, the endocochlear potential (EP) was measured and all animals were sacrificed for histology. At a cisplatin dose of 2.0 mg/kg/day, the time needed to reach the criterion hearing loss varied from 5 to 11 days. With 1.5 mg/kg/day this period lasted longer, the cumulative dose being the first-order predictor. The cochlear potentials gradually recovered in the first 2 weeks after treatment. At the lower frequencies, recovery was often complete. At the higher frequencies complete recovery was never seen. EP was depressed when measured just after treatment but had normal values long after. Basal outer hair cell (OHC) loss was found for both the short and the long post-treatment period. Thus, loss and recovery of cochlear potentials can for a large part be explained by loss and recovery of the EP. Recovery is limited by permanent OHC loss.
Klis
Sjaak F L
SF
Hearing Research Laboratories, University Medical Center, Room G.02.531, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands. s.klis@kmb.azu.nl
O'Leary
Stephen J
SJ
Wijbenga
Jeroen
J
de Groot
John C M J
JC
Hamers
Frank P T
FP
Smoorenburg
Guido F
GF
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D003638:Deafness / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D006801:Humans; D012038:Regeneration / Q000187:drug effects; D013997:Time Factors
D000970:Antineoplastic Agents; D002945:Cisplatin