Fluorocitrate ototoxicity. A morphologic and cytochemical model for primary neural degeneration in the guinea pig cochlea

Ann Otol Rhinol Laryngol. 1976 Mar-Apr;85(2 pt.1):185-97. doi: 10.1177/000348947608500202.

Abstract

Fluorocitrate, an inhibitor of the tricarboxylic acid cycle at the aconitase reaction, produces a time and dose related neural dystrophy in the guinea pig cochlea. There is direct inhibition of succinic dehydrogenase activity but not nicotinamide adenine dinucleotide dehydrogenase and cytochrome oxidase via cytochrome c activities. The dystrophic neural changes morphologically are similar to those noted in primary neural degeneration and neural presbycusis in man. Neural degeneration in aging appears to be the result of a dissociation of biochemical reactions preventing the proper utilization of organic fuel molecules for generation of energy and direct or indirect inhibition of respiration.

MeSH terms

  • Animals
  • Citrates / pharmacology
  • Citrates / toxicity*
  • Cochlear Nerve / drug effects*
  • Cochlear Nerve / enzymology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Electron Transport Complex IV
  • Guinea Pigs
  • Histocytochemistry
  • Mitochondrial Swelling / drug effects
  • Nerve Degeneration / drug effects*
  • Oxidoreductases
  • Succinate Dehydrogenase

Substances

  • Citrates
  • Oxidoreductases
  • Succinate Dehydrogenase
  • Electron Transport Complex IV