Cisplatinum (cis-diamminedichloroplatinum II), an inorganic compound with potent antineoplastic activity against various experimental tumor systems, has been known to have some untoward side effects such as nephrotoxicity, bone marrow depression, and gastrointestinal toxicity, as frequently found in other anticancer drugs. In addition to these side effects, there have been several clinical reports on the ototoxicity of Cisplatinum ; that is, patients treated with large doses of this agent often exhibited tinnitus, temporary or permanent hearing loss for high frequency tones. The purpose of this preliminary study was to examine the possible toxic effect on the organ of Corti of the guinea pig cochleas, and to compare it with the ototoxic aminoglycoside antibiotics and the other agents with ototoxicity.
The results obtained in this study were as follows.
1) Ototoxicity was evaluated by the disappearance of Preyer's pinna-reflex in response to high frequency pure tones and by histopathological examination of the organ of Corti of the guinea pig cochleas with surface preparation technique.
2) The animals treated with repeated intraperitoneal injections of Cisplatinum (e. g., a daily dose of 3mg/kg for 5-7 days for a total of approximately 15-20mg/kg) developed permanent hearing loss and histological lesions with a scattered or an irregular patchy form of the outer hair cell degeneration in the lower-half of the cochlear turns (from the basal end to the second turn of the cochlea). No obvious morphological alteration was observed in a row of the inner hair cells throughout the cochlea by light microscopy.
3) Thus, the lesions appearing in the organ of Corti following administration of Cisplatinum were limited to the outer hair cells and considered to be fairly less severe as compared with the cases of administration of neomycin or nitrogen mustard N-oxide, which had previously been reported by us and the form of the cochlear lesions due to this inorganic agent might be characterized by “patchy degeneration pattern” of the outer hair cells in the lower half of the cochlea.
