Possible mediation of quinolinic acid-induced hippocampal damage by reactive oxygen species.
Several differences exist between quinolinic acid and N-methyl-D-aspartate (NMDA) in the potency and pharmacology of their neurotoxic actions in the brain, suggesting that quinolinic acid may act by mechanisms additional to the activation of NMDA receptors, possibly involving lipid peroxidation. In the present review, studies are considered which have attempted to determine whether free radicals might contribute to the neuronal damage induced by quinolinic acid. Following Injections into the hippocampus of anaesthetised rats, quinolinic acid induced damage is prevented by melatonin, by an action not blocked by the melatonin receptor blocker luzindole. Deprenyl, but not the non-selective monoamine oxidase inhibitor nialamide, also prevent quinolinic acid-induced damage. In vitro, several groups have shown that quinolinic acid can induce lipid peroxidation of brain tissue The results suggest that free radical formation contributes significantly to quinolinic acid-induced damage in vivo.
Stone
T W
TW
Institute of Biomedical & Life Sciences, University of Glasgow, United Kingdom.
Behan
W M
WM
MacDonald
M
M
Darlington
L G
LG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation; D009474:Neurons / Q000187:drug effects; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D017378:Quinolinic Acid