title: Intracochlear administration of thiourea protects against cisplatin-induced outer hair cell loss in the guinea pig.
abstract: Amelioration of cisplatin-induced side-effects is of great clinical importance. Local administration of a cytoprotective agent to the inner ear offers a possibility to prevent cisplatin-induced ototoxicity without risk of interference with the antitumour effect. The ideal substance for local administration has yet to be identified. Thiourea (TU) has unique properties that make it an interesting candidate. This study was initiated to test the hypothesis that TU given by local administration protects against cisplatin ototoxicity in the guinea pig. After baseline auditory brainstem response (ABR) assessment, the left cochlea was implanted with a microtip catheter connected to an osmotic pump filled with either 27 mg/ml TU in artificial perilymph (AP), or AP administered for the full duration of the study. Three days post-implant, animals with normal ABRs received an intravenous injection of 8 mg/kg body-weight cisplatin. Five days after the cisplatin treatment ABRs were reassessed, animals decapitated and bilateral cytocochleograms prepared. TU-treated ears demonstrated significantly lower outer hair cell (OHC) loss as compared to contralateral untreated ears, and significantly lower OHC loss compared to AP-treated ears. ABR threshold shift did not differ significantly between the two groups. It can be postulated that TU demonstrates partial protection against cisplatin-induced ototoxicity.
authors.affiliation: Department of Otorhinolaryngology, Karolinska Hospital, 17176 Stockholm, Sweden. andreas.ekborn@ks.se
authors.forename: A
authors.initials: A
authors.lastname: Ekborn
authors.forename: G
authors.initials: G
authors.lastname: Laurell
authors.forename: H
authors.initials: H
authors.lastname: Ehrsson
authors.forename: J
authors.initials: J
authors.lastname: Miller
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000506:poisoning*; D016923:Cell Death / Q000187:drug effects; D002945:Cisplatin / Q000506:poisoning*; D003051:Cochlea; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology*; D008856:Microscopy, Fluorescence; D013890:Thiourea / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D013890:Thiourea; D002945:Cisplatin