Round window pH manipulation alters the ototoxicity of systemic cisplatin.
The effect of manipulation of pH on the ototoxicity of systemic cisplatin was studied in Wistar rats. After control auditory brainstem responses (ABR) were performed, the auditory bullae were opened and acidic (pH 6.0), neutral (pH 7.4) or basic (pH 9.0) phosphate-buffered saline (PBS) was applied to fill the round window niche (RWN). After 30 min, 13 mg/kg cisplatin solution or saline was administered intraperitoneally. After 3 days, follow-up ABRs were performed and cochleae were processed for morphological analysis. Animals that received basic PBS on the RWN and cisplatin intraperitoneally had significantly smaller ABR threshold shifts compared to rats pretreated with neutral pH buffer (P<0.05). Animals that received acidic PBS on the RWN and systemic cisplatin showed significantly greater ABR threshold shifts compared to those pretreated with neutral pH buffer (P<0.05). No significant threshold changes were observed in animals that received buffer of any pH on the RWN, followed by saline intraperitoneally. Semiquantitative analysis of hair cell survival confirmed a protective effect by basic PBS against cisplatin and a synergistic effect by acidic PBS on cisplatin ototoxicity (P<0.05). It appears that changes in cochlear pH can modulate the ototoxic effects of systemically applied cisplatin.
Tanaka
Fujinobu
F
Department of Surgery, Southern Illinois University School of Medicine, P.O. Box 19638,Springfield, IL 62794-9638, USA.
Whitworth
Craig A
CA
Rybak
Leonard P
LP
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000506:poisoning*; D001309:Auditory Threshold / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000506:poisoning*; D004423:Ear / Q000473:pathology* / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D008297:Male; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D012405:Round Window, Ear / Q000378:metabolism*
D000970:Antineoplastic Agents; D011522:Protons; D002945:Cisplatin