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.
D000818:Animals; D002951:Citrates / Q000494:pharmacology / Q000633:toxicity*; D003056:Cochlear Nerve / Q000187:drug effects* / Q000201:enzymology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV; D006168:Guinea Pigs; D006651:Histocytochemistry; D008933:Mitochondrial Swelling / Q000187:drug effects; D009410:Nerve Degeneration / Q000187:drug effects*; D010088:Oxidoreductases; D013385:Succinate Dehydrogenase
D002951:Citrates; D010088:Oxidoreductases; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV