title: Characterization of the neurotoxicity induced by the extract of Magnistipula butayei (Chrysobalanaceae) in rat: effects of a new natural convulsive agent.
abstract: This study was designed to document convulsant and neurotoxic properties of extracts of a tropical tree, Magnistipula butayei subsp. Montana, and to investigate the involvement of the glutamatergic system in these effects. Continuous behavioral observations and electroencephalographic (EEG) records were obtained after per os administration of an aqueous extract of Magnistipula (MBMAE) in rats. MBMAE (800 mg/kg) induced behavioral changes resembling motor limbic seizures: staring and head tremor, automatisms, forelimb clonic movements and violent tonic-clonic seizures leading to death in all animals. Concomitantly, important seizure activity that gradually evolved to epileptiform activity was recorded on the EEG. Moreover, c-Fos immunohistochemistry has revealed an increased c-Fos expression in the dentate gyrus and in piriform, peri- and entorhinal cortices 2 and 4h after treatment. This expression pattern suggested that the mechanism of action for the MBMAE is similar to that observed in glutamate-induced models of epilepsy. The MBMAE increased cell death also in hippocampal cell cultures. Furthermore, the build-up of convulsive activity and epileptic discharges induced by MBMAE in rat were abolished by MK-801, an NMDA receptor antagonist. Our study suggests that MBMAE contains a potent toxin, with a powerful neurotoxic activity in rat, and corresponding to a new natural component(s) that act as an NMDA-mediated convulsant molecule.
authors: Natural and Synthetic Drugs Research Center (CPSNS), University of Liege, B-4000 Liege, Belgium.
authors: Charles
authors: C
authors: Karangwa
authors: Virginie
authors: V
authors: Esters
authors: Monique
authors: M
authors: Tits
authors: Arlette
authors: A
authors: Minet
authors: André
authors: A
authors: Boland
authors: Vincent
authors: V
authors: Seutin
authors: Alfred
authors: A
authors: Noirfalise
authors: Luc
authors: L
authors: Angenot
authors: Thierry
authors: T
authors: Grisar
authors: Agnès
authors: A
authors: Foidart
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045469:Chrysobalanaceae / Q000737:chemistry*; D003292:Convulsants / Q000032:analysis / Q000633:toxicity*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009498:Neurotoxins / Q000032:analysis / Q000633:toxicity*; D010936:Plant Extracts / Q000032:analysis / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D003292:Convulsants; D009498:Neurotoxins; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate