Seizures induced by fluoroacetic acid and fluorocitric acid may involve chelation of divalent cations in the spinal cord.
Fluoroacetic and fluorocitric acid toxicity is often characterized by seizures, however the mechanism of this activity is unknown. Intrathecal (i.t.) injection of fluorocitrate in mice resulted in seizures after an average latency of 15 s, while intracerebroventricular (i.c.v.) injection produced seizures after 36.5 min, and required higher doses to achieve this effect. This indicates the probable site of fluoroacetate and fluorocitrate neurotoxicity is the spinal cord. To mimic citrate accumulation, characteristic of fluoroacetate and fluorocitrate poisoning, citric acid was injected i.t. and also found to produce seizures. The structurally unrelated compounds EDTA, EGTA, glutamic acid and lactic acid also produced seizures identical to fluorocitrate. The ability of these compounds to chelate Ca2+ correlates well with their ability to cause seizures when administered i.t. and coadministration of calcium greatly attenuated the neurotoxicity of these compounds as well as fluoroacetate and fluorocitrate. In contrast, Ca2+ was unable to inhibit seizures elicited by strychnine, suggesting calcium's ability to inhibit chelators of divalent cations is not due to a general anticonvulsant effect. These results suggest that changes in Ca2+ concentration in the spinal cord may be responsible for some forms of seizure activity.
Hornfeldt
C S
CS
Department of Veterinary Biology, University of Minnesota, St. Paul, MN 55108.
Larson
A A
AA
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000134:cerebrospinal fluid*; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D005463:Fluoroacetates / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013116:Spinal Cord / Q000502:physiology; D013331:Strychnine
D002413:Cations, Divalent; D002614:Chelating Agents; D002951:Citrates; D005463:Fluoroacetates; C007744:fluorocitrate; D013331:Strychnine; D002118:Calcium