Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl
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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 study was designed to examine the effect of a potent antioxidant, melatonin, and the potential neuroprotectant, deprenyl, as inhibitors of quinolinic acid‐induced brain damage. Injections were made into the hippocampus of anaesthetized rats, which were allowed to recover before the brains were taken for histology and the counting of surviving neurones. Quinolinic acid (120 nmols) induced damage to the pyramidal cell layer, which was prevented by the co‐administration of melatonin (5 nmols locally plus 2×20 mg kg−1 i.p.). This protective effect was not prevented by the melatonin receptor blocker luzindole. Neuronal damage produced by NMDA (120 nmols) was not prevented by melatonin. Quinolinic acid increased the formation of lipid peroxidation products from hippocampal tissue and this effect was prevented by melatonin. Deprenyl also prevented quinolinic acid‐induced damage at a dose of 50 nmols but not 10 nmols plus 2×1.0 mg kg−1 i.p. The non‐selective monoamine oxidase inhibitor nialamide (10 and 50 nmols plus 2×25 mg kg−1) did not afford protection. The results suggest that quinolinic acid‐induced neuronal damage can be prevented by a receptor‐independent action of melatonin and deprenyl, agents which can act as a potent free radical scavenger and can increase the activity of endogenous antioxidant enzymes respectively. This suggests that free radical formation contributes significantly to quinolinic acid‐induced damage in vivo. British Journal of Pharmacology (1999) 128, 1754–1760; doi:10.1038/sj.bjp.0702940
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Quinolinic acid contributes to oxidative stress.
“QUIN contributes to oxidative stress”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Behan et al., 1999
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Self-citation
- Authors
- Behan, W. M. H., McDonald, M., Darlington, L. G., & Stone, T. W.
- Affiliations
- University of Glasgow (GB)
- Epsom Hospital (GB)
- Corresponding author
- Stone, T W
- ORCID
- Stone, T W
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1999-12
- Volume
- 128
- Issue
- 8
- Pages
- 1754-1760
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1571800
- OpenAlex
- W2083949851
- Cited by
- 225
- References
- 55
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 12 · 2016: 7 · 2015: 11 · 2014: 7 · 2013: 5 · 2012: 13
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- quinolinic acid, hippocampal neuronal damage, oxidative stress, melatonin, selegiline, excitotoxicity, NMDA receptor, lipid peroxidation, free radical scavenging, neuroprotection, monoamine oxidase inhibition, nialamide, pyramidal neurons, antioxidant enzymes
- MeSH terms
- Animals, Antioxidants, Hippocampus, Male, Melatonin, Selegiline, Lipid Peroxidation, Rats, Wistar, Quinolinic Acid, Oxidative Stress, Neuroprotective Agents, Rats
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