» Articles » PMID: 10721057

Neuroprotective Effects of Kynurenine-3-hydroxylase Inhibitors in Models of Brain Ischemia

Overview
Date 2000 Mar 18
PMID 10721057
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

The neuroprotective effects of two kynurenine hydroxylase inhibitors, (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfona mide (Ro 61-8048), were studied in vitro and in vivo. In organotypic hippocampal slice cultures deprived of oxygen and glucose, these inhibitors significantly reduced neuronal damage. In gerbils subjected to bilateral carotid occlusion for 5 min, the administration of mNBA (400 mg/kg i.p., 3 times) or Ro 61-8048 (40 mg/kg i.p., 3 times) dramatically decreased the percentage of damaged pyramidal neurones in the hippocampal CA1 region. Finally, in rats with permanent occlusion of the middle cerebral artery, mNBA (200-400 mg/kg i.p.) and Ro 61-8048 (40 mg/kg i.p.) administration reduced the infarct volume. Our results demonstrate that ischemic neuronal damage may be significantly decreased by inhibiting kynurenine hydroxylase.

Citing Articles

Cellular Localization of Kynurenine 3-Monooxygenase in the Brain: Challenging the Dogma.

Sathyasaikumar K, la Cruz V, Pineda B, Vazquez Cervantes G, Ramirez Ortega D, Donley D Antioxidants (Basel). 2022; 11(2).

PMID: 35204197 PMC: 8868204. DOI: 10.3390/antiox11020315.


Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders.

Mor A, Tankiewicz-Kwedlo A, Krupa A, Pawlak D Cells. 2021; 10(7).

PMID: 34206739 PMC: 8306609. DOI: 10.3390/cells10071603.


Systematic Review on the Involvement of the Kynurenine Pathway in Stroke: Pre-clinical and Clinical Evidence.

Colpo G, Venna V, McCullough L, Teixeira A Front Neurol. 2019; 10:778.

PMID: 31379727 PMC: 6659442. DOI: 10.3389/fneur.2019.00778.


Kynurenines with neuroactive and redox properties: relevance to aging and brain diseases.

Reyes Ocampo J, Lugo Huitron R, Gonzalez-Esquivel D, Ugalde-Muniz P, Jimenez-Anguiano A, Pineda B Oxid Med Cell Longev. 2014; 2014:646909.

PMID: 24693337 PMC: 3945746. DOI: 10.1155/2014/646909.


Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration.

Zwilling D, Huang S, Sathyasaikumar K, Notarangelo F, Guidetti P, Wu H Cell. 2011; 145(6):863-74.

PMID: 21640374 PMC: 3118409. DOI: 10.1016/j.cell.2011.05.020.