Effects of a single high dose of cisplatin on the melanocytes of the stria vascularis in the guinea pig.
The antineoplastic drug cisplatin is known to cause a reduction in endocochlear potential. The hypothesis to be tested was whether a single high dose of cisplatin affects the melanocytes by altering the expression of melanin. Pigmented guinea pigs received a bolus injection of cisplatin (8 mg/kg as a 15-second intravenous infusion). Auditory brainstem response (ABR) thresholds and morphological analysis of the hair cells and the stria vascularis were made 96 h after injection. ABR thresholds were elevated (15-40 dB) at 12-30 kHz and a significant loss of outer hair cells in the more basal regions was found. Cisplatin caused a significantly lower density of melanin in the intermediate cells in the basal region without any signs of apoptosis. Changes in melanin content were not noted in the middle or apical cochlear regions. Significant correlations were found between melanin density, ABR threshold shifts and outer hair cell loss in the region corresponding to 30 kHz. The findings reported here further support the multiple cytotoxic effect of cisplatin on the inner ear.
Laurell
Göran
G
Department of Clinical Sciences, Umeå University, Umeå, Sweden. goran.laurell@ent.umu.se
Ekborn
Andreas
A
Viberg
Agneta
A
Canlon
Barbara
B
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013316:Stria Vascularis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D000970:Antineoplastic Agents; D002945:Cisplatin