Behavioral toxicity of guanidinosuccinic acid in adult and young mice.
Guanidinosuccinic acid (GSA), a guanidino compound found to be greatly increased in uremia, was administered by intraperitoneal (i.p.) injection to adult albino mice and to young mice 7, 14 and 21 days old. Epileptogenic and toxic properties were assessed and GSA brain levels following i.p. injection were determined. In adult mice, GSA induced long-lasting generalized clonic and clonic-tonic convulsions in a dose-dependent manner with a CD50 (and 95% confidence interval) of 363 (287-458) mg/kg (n = 35), and an LD50 of 579 (445-756) mg/kg. The CD50 of GSA corresponded with a brain concentration of 56 nmol/g tissue. Electrocorticographic recording in five adult mice revealed epileptiform discharges (spikes, spike-waves, and polyspike-waves) which appeared concomitant with the convulsions. When young mice were i.p. injected with a (for adults) subconvulsive dose of GSA (250 mg/kg), an age-dependent decrease was noted in GSA-induced convulsions and in the resulting brain concentration. The presented findings suggest that GSA could be an important uremic toxin which could contribute to the epileptic symptomatology in uremia.
D'Hooge
R
R
Laboratory of Neurochemistry and Behavior, Born-Bunge Foundation, University of Antwerp (UIA), Belgium.
Pei
Y Q
YQ
Marescau
B
B
De Deyn
P P
PP
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D004569:Electroencephalography; D005260:Female; D006146:Guanidines / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051379:Mice; D012640:Seizures / Q000139:chemically induced; D013386:Succinates / Q000378:metabolism / Q000633:toxicity*
D006146:Guanidines; D013386:Succinates; C001318:guanidinosuccinic acid