Calpain immunoreactivity and morphological damage in chinchilla inner ears after carboplatin.
Carboplatin produces an unusual pattern of damage in the chinchilla inner ear, characterized by early destruction of type I afferent fibers and preferential loss of type I hair cells in the vestibular end organs and inner hair cells (IHCs) in the cochlea. In the present study, we investigated a potential role of calpains, a family of calcium-activated proteases, in carboplatin ototoxicity. Chinchillas received carboplatin (100 mg/kg IP) and were sacrificed 12, 24, 48, or 72 h later for morphological evaluation or immunocytochemistry. Nerve fibers and myelin were the initial sites of increased calpain immunoreactivity (IR) and morphological damage. At 12 h, granular immunoreactive puncta were present within nerve fibers and their myelin sheaths in the spiral ganglion. In the habenula perforata, dense reaction product was present in large vacuoles in the myelin surrounding the nerve fibers. At 24 h, nerve fibers and myelin were destroyed in the habenula, and those in the spiral ganglion showed increased calpain IR and morphological damage. At 72 h, nerve fibers and myelin were completely destroyed. Calpain IR was not a prominent feature of IHCs, type I vestibular hair cells, or ganglion cells at any time after carboplatin. The results show a correlation between calpain IR and carboplatin-induced axon and myelin degeneration. We propose that calpain-induced axonopathy and myelinopathy are primary features of carboplatin ototoxicity in chinchilla.
Ding
Lian
L
Center for Hearing and Deafness, University of Buffalo, NY 14214, USA.
McFadden
Sandra L
SL
Salvi
Richard J
RJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002154:Calpain / Q000378:metabolism*; D016190:Carboplatin / Q000494:pharmacology*; D002682:Chinchilla; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007758:Ear, Inner / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D012016:Reference Values; D013997:Time Factors; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D016190:Carboplatin; D002154:Calpain