Effects of carboplatin on amino acid chemistry in chinchilla cochlear nucleus

Hear Res. 2002 Mar;165(1-2):19-29. doi: 10.1016/s0378-5955(01)00389-6.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / analysis*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology*
  • Cell Survival / drug effects
  • Chinchilla
  • Cochlear Nucleus / chemistry*
  • Cochlear Nucleus / drug effects*
  • Cochlear Nucleus / metabolism
  • Glutaminase / metabolism
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / physiology
  • Injections, Intraperitoneal
  • Lipid Metabolism
  • Osmolar Concentration
  • Reference Values
  • Tissue Distribution

Substances

  • Amino Acids
  • Antineoplastic Agents
  • Carboplatin
  • Glutaminase