Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl

Citation
Wmh. Behan et al., Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl, BR J PHARM, 128(8), 1999, pp. 1754-1760
Citations number
55
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
00071188 → ACNP
Volume
128
Issue
8
Year of publication
1999
Pages
1754 - 1760
Database
ISI
SICI code
0007-1188(199912)128:8<1754:OSAAMF>2.0.ZU;2-6
Abstract
1 There are differences between the excitotoxic actions of quinolinic acid and N-methyl-D-aspartate (NMDA) which suggest that quinolinic acid may act by mechanisms additional to the activation of NMDA receptors. The present s tudy was designed to examine the effect of a potent antioxidant, melatonin, and the potential neuroprotectant, deprenyl, as inhibitors of quinolinic a cid-induced brain damage. Injections were made into the hippocampus of anae sthetized rats, which were allowed to recover before the brains were taken for histology and the counting of surviving neurones. 2 Quinolinic acid (120 nmols) induced damage to the pyramidal cell layer, w hich was prevented by the co-administration of melatonin (5 nmols locally p lus 2 x 20 mg kg(-1) i.p.). This protective effect was not prevented by the melatonin receptor blocker luzindole. Neuronal damage produced by NMDA (12 0 nmols) was not prevented by melatonin. 3 Quinolinic acid increased the formation of lipid peroxidation products fr om hippocampal tissue and this effect was prevented by melatonin. 4 Deprenyl also prevented quinolinic acid-induced damage at a dose of 50 nm ols but not 10 nmols plus 2 x 1.0 mg kg(-1) i.p. The non-selective monoamin e oxidase inhibitor nialamide(10 and 50 nmols plus 2 x 25 mg kg(-1)) did no t afford protection. 5 The results suggest that quinolinic acid-induced neuronal damage can be p revented by a receptor-independent action of melatonin and deprenyl, agents which can act as a potent free radical scavenger and can increase the acti vity of endogenous antioxidant enzymes respectively. This suggests that fre e radical formation contributes significantly to quinolinic acid-induced da mage in vivo.