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

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.