Characterization of the neurotoxicity induced by the extract of Magnistipula butayei (Chrysobalanaceae) in rat: Effects of a new natural convulsive agent
[en] 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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Karangwa, Charles; Université Nationale du Rwanda - UNR > Pharmacie
Esters, Virginie ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Tits, Monique ; Université de Liège - ULiège > Département de pharmacie > Phytochimie et phytothérapie
Minet, Arlette ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Boland, André ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Seutin, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Noirfalise, Alfred ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Angenot, Luc ; Université de Liège - ULiège > Département de pharmacie > Pharmacognosie
Grisar, Thierry ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Foidart, Agnès ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Service administratif de la Faculté (Médecine)
Language :
English
Title :
Characterization of the neurotoxicity induced by the extract of Magnistipula butayei (Chrysobalanaceae) in rat: Effects of a new natural convulsive agent
Publication date :
15 June 2007
Journal title :
Toxicon
ISSN :
0041-0101
eISSN :
1879-3150
Publisher :
Pergamon-Elsevier Science Ltd, Oxford, United Kingdom
Volume :
49
Issue :
8
Pages :
1109-1119
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Centre Interfacultaire de Recherche du Médicament (C.I.R.M.)
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