Neuroprotective effect of free radical scavengers on beta-N-oxalylamino-L-alanine (BOAA)-induced neuronal damage in rat hippocampus.
The neurotoxin beta-N-oxalylamino-L-alanine (BOAA), found in Lathyrus sativus seeds, is thought to be the causative agent of neurolathyrism. We have investigated the neuroprotective effects of free radical scavengers on BOAA-induced toxicity following focal injection (1 microliter) of BOAA and comparing the pathological outcome with the effects of injections of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainate (KA) or N-methyl-D-aspartate (NMDA) into the dorsal hippocampus of male Wistar rats. Cellular damage was assessed histologically. BOAA (50 nmol) induced a highly selective pattern of hippocampal damage identical with that seen with AMPA (1 nmol). BOAA-induced neurotoxicity, but not AMPA, KA (0.5 nmol) or NMDA (25 nmol)-induced neurotoxicity, was prevented in a dose-dependent manner by focal co-injection of four potential free radical scavengers; dimethyl sulphoxide (DMSO) (1750-7000 nmol), dimethylthiourea (DMTU) (8000 nmol), dimethylformamide (DMF) (7000 nmol) and mannitol (1000 nmol). These findings suggest that hippocampal damage induced by BOAA involves an interaction between AMPA receptors and free radicals.
Willis
C L
CL
Department of Neurology, Institute of Psychiatry, London, UK.
Meldrum
B S
BS
Nunn
P B
PB
Anderton
B H
BH
Leigh
P N
PN
D000818:Animals; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016472:Motor Neuron Disease / Q000139:chemically induced*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D016166:Free Radical Scavengers; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid