Cisplatin-induced ototoxicity: morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs?
Cisplatin is frequently used in the treatment of various forms of malignancies. Its therapeutic efficacy, however, is limited by the occurrence of sensorineural hearing loss. Little is known about the course of hearing loss over longer time intervals after cessation of cisplatin administration. Infrequently, recovery of hearing has been described in animals and humans. Stengs et al. (1997) treated guinea pigs with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days and subsequently studied cochlear function after survival times varying from 1 day to 16 weeks. Spontaneous improvement of the hair cell-related potentials (cochlear microphonics and summating potentials) was observed starting 2 weeks after cessation of treatment. In the present study we examined light microscopically the cochleas used in the study of Stengs et al. (1997). One day after cessation of cisplatin administration outer hair cell (OHC) loss in the basal cochlear turn averaged 66%. In the 1-week survival group, OHC counts were similar to those of the 1-day survival group. In the 4-week survival group, however, a relatively small loss of OHCs was found in the basal cochlear turn; OHC loss averaged only 15%. A similar loss was found after 8 weeks. In the 16-week survival group, OHC loss in the basal turn increased to 48%, but this was not statistically significant. Our histological observations are in line with the electrophysiological data from the same animals. Our findings suggest that OHCs recover from cisplatin-induced damage 1-4 weeks after treatment. However, the results do not allow a conclusion as to whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs.
Cardinaal
R M
RM
Hearing Research Laboratories, Department of Otorhinolaryngology, University Medical Center, Room G.02.531, P.O. Box 85.500, 3508 GA, Utrecht, The Netherlands.
de Groot
J C
JC
Huizing
E H
EH
Veldman
J E
JE
Smoorenburg
G F
GF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001306:Auditory Pathways / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000506:poisoning*; D007758:Ear, Inner / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018159:Endolymphatic Hydrops / Q000139:chemically induced; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009475:Neurons, Afferent / Q000473:pathology; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D020127:Recovery of Function; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D013316:Stria Vascularis / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D002945:Cisplatin