Effects of carboplatin on amino acid chemistry in chinchilla cochlear nucleus.
Carboplatin, a drug widely used against solid head and neck tumors, selectively destroys cochlear inner hair cells and type I auditory nerve fibers in chinchilla. This should affect neurotransmitter chemistry, involving amino acids, where the type I auditory nerve fibers terminate in the cochlear nucleus. Using microdissection combined with high-performance liquid chromatography, amino acid concentrations were mapped in the cochlear nuclei of chinchillas injected intraperitoneally 6-8 weeks earlier with 100 mg/kg carboplatin and in those of control animals. Glutamate concentrations were 23% lower in the anteroventral cochlear nucleus (AVCN) and 40% lower in the posteroventral cochlear nucleus (PVCN) of carboplatin-injected chinchillas as compared to controls, while aspartate concentrations were 18% lower in AVCN and 27% lower in PVCN. Using a fluorometric assay, activities of glutaminase, an enzyme which catalyzes glutamate synthesis, were 30% lower in AVCN and 38% lower in PVCN of carboplatin-injected chinchillas. Concentrations of glutamine, gamma-aminobutyrate, and glycine were also lower in some ventral and dorsal cochlear nucleus regions of treated animals. These changes probably result mainly from both primary and later effects of reduced type I auditory nerve fiber input to the cochlear nucleus.
Li
Yingzhe
Y
Department of Otolaryngology - Head and Neck Surgery, Medical College of Ohio, 3065 Arlington Avenue, Toledo 43614, USA.
Godfrey
Donald A
DA
Godfrey
Matthew A
MA
Ding
Da-lian
DL
Salvi
Richard
R
D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002682:Chinchilla; D017626:Cochlear Nucleus / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D050356:Lipid Metabolism; D009994:Osmolar Concentration; D012016:Reference Values; D014018:Tissue Distribution
D000596:Amino Acids; D000970:Antineoplastic Agents; D016190:Carboplatin; D005972:Glutaminase