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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Autores principales:	Ewelina Bratek-Gerej, Apolonia Ziembowicz, Jakub Godlewski, Elzbieta Salinska
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	neonatal hypoxia–ischemia kynurenic acid (KYNA) oxidative stress neuroprotection Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/93a58beeddcc4ebeb74d1e4501a38547
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spelling	oai:doaj.org-article:93a58beeddcc4ebeb74d1e4501a385472021-11-25T16:28:18ZThe Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress10.3390/antiox101117752076-3921https://doaj.org/article/93a58beeddcc4ebeb74d1e4501a385472021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1775https://doaj.org/toc/2076-3921The 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.Ewelina Bratek-GerejApolonia ZiembowiczJakub GodlewskiElzbieta SalinskaMDPI AGarticleneonatal hypoxia–ischemiakynurenic acid (KYNA)oxidative stressneuroprotectionTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1775, p 1775 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neonatal hypoxia–ischemia kynurenic acid (KYNA) oxidative stress neuroprotection Therapeutics. Pharmacology RM1-950
spellingShingle	neonatal hypoxia–ischemia kynurenic acid (KYNA) oxidative stress neuroprotection Therapeutics. Pharmacology RM1-950 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
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.
format	article
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
title	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_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_sort	mechanism of the neuroprotective effect of kynurenic acid in the experimental model of neonatal hypoxia–ischemia: the link to oxidative stress
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/93a58beeddcc4ebeb74d1e4501a38547
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The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia–Ischemia: The Link to Oxidative Stress

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