Influence of pH on the ototoxicity of cisplatin: a round window application study.
Cisplatin is an antineoplastic agent that produces a number of dose-limiting side effects, including ototoxicity. We investigated the effect of pH on cisplatin ototoxicity. Auditory brainstem responses (ABR) were recorded in chinchillas. Then the auditory bullae were opened and acidic (pH=6.5), neutral (pH=7.4) or alkaline (pH=10.2) phosphate-buffered saline (PBS) was applied to the round window membrane. After 30 min, any remaining solution was removed and cisplatin solution was applied to the round window membrane. After 3 days, follow-up ABRs were performed and the cochleae were processed for morphological analysis. Neutral PBS+cisplatin administration resulted in profound threshold changes at all frequencies. Acidic PBS+cisplatin administration showed had a trend of increased threshold changes, but the change did not reach statistical significance. However, the degree of hair cell loss was significantly higher than that of the neutral PBS-cisplatin group. Alkaline PBS significantly reduced cisplatin-induced threshold changes (P<0.05) compared to the neutral PBS group. Because the pH of cisplatin solution was 6.0, pH 6.0 PBS was applied to round window membrane. This acidic PBS solution did not cause any hearing impairment. These results demonstrate that pH can modulate the ototoxic effects of cisplatin.
Tanaka
Fujinobu
F
Department of Surgery, Southern Illinois University School of Medicine, PO Box 19638, Springfield, IL 62794-9638, USA.
Whitworth
Craig A
CA
Rybak
Leonard P
LP
D000818:Animals; D002021:Buffers; D002452:Cell Count; D002682:Chinchilla; D002945:Cisplatin / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000473:pathology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008855:Microscopy, Electron, Scanning; D010710:Phosphates; D012405:Round Window, Ear / Q000187:drug effects* / Q000648:ultrastructure; D012965:Sodium Chloride / Q000494:pharmacology
D002021:Buffers; D010710:Phosphates; D012965:Sodium Chloride; D006859:Hydrogen; D002945:Cisplatin