Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.
The effects of a common industrial solvent, trichloroethylene (TCE), which was once used as an anesthetic agent but its in vivo mechanism is still unknown, on convulsant-induced seizures in mice were examined. Pretreatment with TCE (250-2000 mg/kg, i.p.) significantly increased pentylenetetrazol (PTZ)-, picrotoxin (PIC)-, bicuculline (BIC)-, strychnine (STY)-, 4-aminopyridine (4-AP)- and N-methyl-D-aspartate (NMDA)-induced convulsion thresholds and lethal doses. However, the increase in convulsion thresholds and lethal doses was much greater for GABAergic antagonists (PIC, BIC, and PTZ) than non-GABAergic convulsants (STY, 4AP, and NMDA) following 2000 mg/kg TCE administration. Pre-treatment of mice with disulfiram (an inhibitor of CYP 4502E1) but not 4-methyl pyrazole (an inhibitor of alcohol dehydrogenase) significantly prolonged the time required for TCE (5000 mg/kg, i.p.) to induce the loss of righting reflex. These results suggest that acute exposure to TCE differentially alters the susceptibility to chemically induced convulsions in mice. The anticonvulsive effect of TCE may be predominantly mediated by GABA(A) receptors. In addition, TCE appears to exert a direct anesthetic effect.
Shih
C L
CL
Department of Pharmacology, Tzu Chi University, 701 Section 3, Chung Yang Road, Hualien 970, Taiwan.
Chen
H H
HH
Chiu
T H
TH
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000931:Antidotes / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology* / Q000633:toxicity; D004221:Disulfiram / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000077604:Fomepizole; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology / Q000633:toxicity; D011720:Pyrazoles / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D012997:Solvents / Q000494:pharmacology*; D014241:Trichloroethylene / Q000494:pharmacology*
D000927:Anticonvulsants; D000931:Antidotes; D003292:Convulsants; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D012997:Solvents; D014241:Trichloroethylene; D000077604:Fomepizole; D004221:Disulfiram; D010433:Pentylenetetrazole