The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress
The over-activation of NMDA receptors and oxidative stress are important components of neonatal hypoxia–ischemia (HI). Kynurenic acid (KYNA) acts as an NMDA receptor antagonist and is known as a reactive oxygen species (ROS) scavenger, which makes it a potential therapeutic compound. This study aime...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/11/1775 |
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| author | Ewelina Bratek-Gerej Apolonia Ziembowicz Jakub Godlewski Elzbieta Salinska |
| author_facet | Ewelina Bratek-Gerej Apolonia Ziembowicz Jakub Godlewski Elzbieta Salinska |
| author_sort | Ewelina Bratek-Gerej |
| collection | DOAJ |
| description | The over-activation of NMDA receptors and oxidative stress are important components of neonatal hypoxia–ischemia (HI). Kynurenic acid (KYNA) acts as an NMDA receptor antagonist and is known as a reactive oxygen species (ROS) scavenger, which makes it a potential therapeutic compound. This study aimed to establish the neuroprotective and antioxidant potential of KYNA in an experimental model of HI. HI on seven-day-old rats was used as an experimental model. The animals were injected i.p. with different doses of KYNA 1 h or 6 h after HI. The neuroprotective effect of KYNA was determined by the measurement of brain damage and elements of oxidative stress (ROS and glutathione (GSH) level, SOD, GPx, and catalase activity). KYNA applied 1 h after HI significantly reduced weight loss of the ischemic hemisphere, and prevented neuronal loss in the hippocampus and cortex. KYNA significantly reduced HI-increased ROS, GSH level, and antioxidant enzyme activity. Only the highest used concentration of KYNA showed neuroprotection when applied 6 h after HI. The presented results indicate induction of neuroprotection at the ROS formation stage. However, based on the presented data, it is not possible to pinpoint whether NMDA receptor inhibition or the scavenging abilities are the dominant KYNA-mediated neuroprotective mechanisms. |
| first_indexed | 2024-03-10T05:45:19Z |
| format | Article |
| id | doaj.art-93a58beeddcc4ebeb74d1e4501a38547 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T05:45:19Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-93a58beeddcc4ebeb74d1e4501a385472023-11-22T22:13:31ZengMDPI AGAntioxidants2076-39212021-11-011011177510.3390/antiox10111775The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative StressEwelina Bratek-Gerej0Apolonia Ziembowicz1Jakub Godlewski2Elzbieta Salinska3Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, PolandDepartment of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, PolandTumor Microenvironment Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, PolandDepartment of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, PolandThe over-activation of NMDA receptors and oxidative stress are important components of neonatal hypoxia–ischemia (HI). Kynurenic acid (KYNA) acts as an NMDA receptor antagonist and is known as a reactive oxygen species (ROS) scavenger, which makes it a potential therapeutic compound. This study aimed to establish the neuroprotective and antioxidant potential of KYNA in an experimental model of HI. HI on seven-day-old rats was used as an experimental model. The animals were injected i.p. with different doses of KYNA 1 h or 6 h after HI. The neuroprotective effect of KYNA was determined by the measurement of brain damage and elements of oxidative stress (ROS and glutathione (GSH) level, SOD, GPx, and catalase activity). KYNA applied 1 h after HI significantly reduced weight loss of the ischemic hemisphere, and prevented neuronal loss in the hippocampus and cortex. KYNA significantly reduced HI-increased ROS, GSH level, and antioxidant enzyme activity. Only the highest used concentration of KYNA showed neuroprotection when applied 6 h after HI. The presented results indicate induction of neuroprotection at the ROS formation stage. However, based on the presented data, it is not possible to pinpoint whether NMDA receptor inhibition or the scavenging abilities are the dominant KYNA-mediated neuroprotective mechanisms.https://www.mdpi.com/2076-3921/10/11/1775neonatal hypoxia–ischemiakynurenic acid (KYNA)oxidative stressneuroprotection |
| spellingShingle | Ewelina Bratek-Gerej Apolonia Ziembowicz Jakub Godlewski Elzbieta Salinska The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress Antioxidants neonatal hypoxia–ischemia kynurenic acid (KYNA) oxidative stress neuroprotection |
| title | The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress |
| title_full | The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress |
| title_fullStr | The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress |
| title_full_unstemmed | The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress |
| title_short | The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress |
| title_sort | mechanism of the neuroprotective effect of kynurenic acid in the experimental model of neonatal hypoxia ischemia the link to oxidative stress |
| topic | neonatal hypoxia–ischemia kynurenic acid (KYNA) oxidative stress neuroprotection |
| url | https://www.mdpi.com/2076-3921/10/11/1775 |
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