TY - JOUR
T1 - Seizures induced by fluoroacetic acid and fluorocitric acid may involve chelation of divalent cations in the spinal cord
AU - Hornfeldt, Carl S.
AU - Larson, Alice A.
PY - 1990/4/25
Y1 - 1990/4/25
N2 - 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, critic 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.
AB - 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, critic 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.
UR - http://www.scopus.com/inward/record.url?scp=0025216634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025216634&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(90)90170-B
DO - 10.1016/0014-2999(90)90170-B
M3 - Article
C2 - 2364992
AN - SCOPUS:0025216634
VL - 179
SP - 307
EP - 313
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -