Comparative ototoxicity of cisplatin during acute and chronic treatment.
Functional and morphological alterations were compared in guinea pig cochleae treated acutely (7.5 mg/kg x 2) and chronically (1.5 mg/kg x 10) with cisplatin. Drastic and rapid hearing impairments using compound action potential were observed only after the second injection during acute treatment. During chronic treatment, threshold changes were observed abruptly after 8 or 9 days of treatment. Morphological changes of outer hair cells were stronger in the acute treatment than the chronic one, and they appeared to concur with the functional data. Partial damage in the stria vascularis was observed only after acute treatment. From these results, it was suspected that acute and chronic ototoxic mechanisms differed according to the pharmacokinetics of cisplatin in the inner ear fluid and tissues.
Department of Otolaryngology, Fukui Medical School, Japan.
T
T
Saito
J M
JM
Aran
D000818:Animals; D001309:Auditory Threshold; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D006311:Hearing Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008854:Microscopy, Electron; D013997:Time Factors
D002945:Cisplatin