On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress
Abstract
Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (OH) under controlled conditions of free radical production. In this work we evaluated the ability of KYNA to scavenge superoxide anion (O(2)(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: OH=O(2)(-)>ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 μM) were tested in cerebellum and forebrain homogenates exposed to 5 μM FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 μM), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 μM) in a biological preparation free of these receptors - defolliculated Xenopus laevis oocytes - incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner. In addition, the in vivo formation of OH evoked by an acute infusion of FeSO(4) (100 μM) in the rat striatum was estimated by microdialysis and challenged by a topic infusion of KYNA (1 μM). FeSO(4) increased the striatal OH production, while KYNA mitigated this effect. Altogether, these data strongly suggest that KYNA, in addition to be a well-known antagonist acting on nicotinic and NMDA receptors, can be considered as a potential endogenous antioxidant.
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Peripheral kynurenic acid may be involved in the pathophysiology of MDD through its antioxidative activity on reactive oxygen species.
“peripheral kynurenic acid may be involved in the pathophysiology of MDD through its antioxidative activity on reactive oxygen species (Lugo-Huitron et al., 2011).”
From Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naïve patients with major depressive disorder: An exploratory pilot case-control study (2018) · cites this paper as Lugo-Huitron et al., 2011
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- Authors
- Lugo-Huitrón, R., Blanco-Ayala, T., Ugalde-Muñiz, P., Carrillo-Mora, P., Pedraza-Chaverrí, J., Silva-Adaya, D., Maldonado, P. D., Torres, I., Pinzón, E., Ortiz-Islas, E., López, T., García, E., Pineda, B., Torres-Ramos, M., Santamaría, A., & La Cruz, V. P.-D.
- Affiliations
- Instituto Nacional de Neurología y Neurocirugía (MX)
- Universidad Nacional Autónoma de México (MX)
- Venue
- Neurotoxicology and Teratology
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 33
- Issue
- 5
- Pages
- 538-547
- ISSN
- 0892-0362 (ISSN-L)
- OpenAlex
- W2087714907
- Cited by
- 346
- References
- 59
- Citations by year
- 2026: 25 · 2025: 21 · 2024: 29 · 2023: 34 · 2022: 40 · 2021: 40 · 2020: 18 · 2019: 18 · 2018: 27 · 2017: 22 · 2016: 23 · 2015: 16 · 2014: 12 · 2013: 9 · 2012: 11
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurotoxicology and Teratology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- kynurenic acid, antioxidant activity, free radical scavenging, oxidative stress, lipid peroxidation, reactive oxygen species, superoxide, peroxynitrite, hydroxyl radicals, NMDA receptor antagonists, alpha7 nicotinic acetylcholine receptor, kynurenine pathway, tryptophan metabolism, 3-nitropropionic acid, iron-induced oxidative stress
- MeSH terms
- Animals, Antioxidants, Cells, Cultured, Cerebellum, Corpus Striatum, Dose-Response Relationship, Drug, Ferrous Compounds, Hydroxides, Kynurenic Acid, Male, Microinjections, Nitro Compounds, Oocytes, Propionates, Xenopus laevis, Lipid Peroxidation, Free Radical Scavengers, Prosencephalon, Rats, Wistar, Reactive Oxygen Species, Oxidative Stress, Rats
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