title: Comparison of cochlear cell death caused by cisplatin, alone and in combination with furosemide.
abstract: Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis.
authors.affiliation: 1Department of Otolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiao Tong University, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.forename: Zhengnong
authors.initials: Z
authors.lastname: Chen
authors.forename: Kaiming
authors.initials: K
authors.lastname: Su
authors.forename: Shankai
authors.initials: S
authors.lastname: Yin
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005665:Furosemide / Q000633:toxicity*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D011897:Random Allocation; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests
chemical_list: D005665:Furosemide; D002945:Cisplatin
keywords: auditory brain-stem response; cisplatin; furosemide; hair cell; spiral ganglion neuron.; totoxicity
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