Article (Scientific journals)
Pre- and post-treatment with pirlindole and dehydropirlindole protects cultured brain cells against nitric oxide-induced death.
Boland, André; Gérardy, Jean; Mossay, Danielle et al.
2003In European Journal of Pharmacology, 466, p. 21-30
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Keywords :
Pirlindole; Brain cells; nitric oxyde
Abstract :
[en] We have previously shown that pirlindole and dehydropirlindole, two monoamine oxidase type-A inhibitors, protect cultured brain cells against iron-induced toxicity through a mechanism unrelated to monoamine oxidase type-A inhibition. The current study was performed to test whether the protective effect of pirlindole and dehydropirlindole could be extended to a nitric oxide (NO)-induced insult. A comparison with other monoamine oxidase inhibitors (brofaromine, moclobemide and deprenyl) and with trolox was made. In a first series of experiments, rat hippocampal or cortical cultured cells were exposed to a drug for 3 h, then 5 muM sodium nitroprusside, a NO donor, was added and the incubation was continued for 16 h. Cell survival assessment showed that pirlindole, dehydropirlindole and trolox significantly protected cultures against NO-induced toxicity in a concentration-dependent manner with respective EC50's of 7, 3 and 17 muM. Similarly, pirlindole, dehydropirlindole or trolox, at a concentration of 50 muM, significantly decreased both intracellular peroxide production and lipoperoxidation. Other drugs were ineffective. In a post-hoc treatment protocol (3- or 6-h pre-incubation in the presence of sodium nitroprusside, then addition of one of the above mentioned compounds), only pirlindole and dehydropirlindole significantly improved cell survival in a concentration-dependent manner with respective EC50'S of 9 and 4 muM. The maximal protection in terms of cell survival was 90% and 78% after 3 and 6 h, respectively. They also reduced the production of both lipoperoxides and endoperoxides. Our results show that pirlindole and dehydropirlindole protect neurons against NO-induced toxicity at pharmacologically relevant concentrations. Moreover, their protective effect is still apparent when they are applied after the start of the insult. Therefore, our preclinical study suggests a new strategy that may be efficient to reduce NO-induced damage in the central nervous system. (C) 2003 Elsevier Science B.V. All rights reserved.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Boland, André ;  Université de Liège - ULiège > Centre d'oncologie
Gérardy, Jean;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Mossay, Danielle ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Seutin, Vincent 
Language :
English
Title :
Pre- and post-treatment with pirlindole and dehydropirlindole protects cultured brain cells against nitric oxide-induced death.
Publication date :
30 May 2003
Journal title :
European Journal of Pharmacology
ISSN :
0014-2999
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
466
Pages :
21-30
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 April 2010

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