Influence of Cyclooxygenase-2 Inhibitors on Kynurenic Acid Production in Rat Brain in Vitro

被引：10

作者：

Zakrocka, Izabela ^{[1
]}

Targowska-Duda, Katarzyna M. ^{[2
]}

Wnorowski, Artur ^{[2
]}

Kocki, Tomasz ^{[1
]}

Jozwiak, Krzysztof ^{[2
]}

Turski, Waldemar A. ^{[1
]}

机构：

[1] Med Univ Lublin, Dept Expt & Clin Pharmacol, Jaczewskiego 8b, PL-20090 Lublin, Poland

[2] Med Univ Lublin, Dept Biopharm, Chodzki 4a, PL-20093 Lublin, Poland

来源：

NEUROTOXICITY RESEARCH | 2019年 / 35卷 / 01期

关键词：

Kynurenic acid; Central nervous system; Cyclooxygenase-2; inhibitors; Inflammation; ACTIVE METABOLITE VALDECOXIB; GLUTAMATE RELEASE; INDUCIBLE CYCLOOXYGENASE; CELECOXIB AUGMENTATION; DOPAMINERGIC-NEURONS; COGNITIVE DEFICITS; SYNAPTIC ACTIVITY; PARECOXIB SODIUM; COX-2; EXPRESSION; CONTROLLED-TRIAL;

D O I：

10.1007/s12640-018-9952-9

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Significant body of evidence suggests that abnormal kynurenic acid (KYNA) level is involved in the pathophysiology of central nervous system disorders. In the brain, KYNA is synthesized from kynurenine (KYN) by kynurenine aminotransferases (KATs), predominantly by KAT II isoenzyme. Blockage of ionotropic glutamate (GLU) receptors is a main cellular effect of KYNA. High KYNA levels have been linked with psychotic symptoms and cognitive dysfunction in animals and humans. As immunological imbalance and impaired glutamatergic neurotransmission are one of the crucial processes in neurological pathologies, we aimed to analyze the effect of anti-inflammatory agents, inhibitors of cyclooxygenase-2 (COX-2): celecoxib, niflumic acid, and parecoxib, on KYNA synthesis and KAT II activity in rat brain in vitro. The influence of COX-2 inhibitors was examined in rat brain cortical slices and on isolated KAT II enzyme. Niflumic acid and parecoxib decreased in a dose-dependent manner KYNA production and KAT II activity in rat brain cortex in vitro, whereas celecoxib was ineffective. Molecular docking results suggested that niflumic acid and parecoxib interact with an active site of KAT II. In conclusion, niflumic acid and parecoxib are dual COX-2 and KAT II inhibitors.

引用

页码：244 / 254

页数：11

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