Antioxidative effects of cysteinyl leukotriene receptor antagonists montelukast and HAMI 3379 on ischemic injury in rat cortical neurons in vitro.
- Author:
Dong-min XU
1
;
Xia-yan ZHANG
1
;
Xiao-rong WANG
1
;
Lu CHEN
2
;
Li-hui ZHANG
3
;
Qiao-juan SHI
1
;
San-hua FANG
1
;
Yun-bi LU
1
;
Wei-ping ZHANG
1
;
Er-qing WEI
1
Author Information
- Publication Type:Journal Article
- MeSH: Acetates; pharmacology; Animals; Antioxidants; pharmacology; Cell Hypoxia; drug effects; Cell Survival; drug effects; Cells, Cultured; Cerebral Cortex; cytology; Cyclohexanecarboxylic Acids; pharmacology; Leukotriene Antagonists; pharmacology; Neurons; drug effects; metabolism; Phthalic Acids; pharmacology; Quinolines; pharmacology; Rats; Reactive Oxygen Species; metabolism
- From: Journal of Zhejiang University. Medical sciences 2014;43(3):257-264
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro.
METHODSCultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/R）or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined. Meanwhile, RNA interference was used to inhibit the expression of CysLT1R and CysLT2R，and the effects were observed.
RESULTSROS production in neurons was significantly increased after 1 h OGD, which reached the peak at 30 min and lasted for 1.5 h after recovery. Montelukast and HAMI 3379 at 0.01-1μmol/L moderately decreased OGD/R-induced ROS production (P<0.05). Montelukast mildly attenuated OGD/R-induced MMP depolarization (P<0.05)，but HAMI 3379 had no effect. H2O2 reduced neuronal viability and increased LDH release, namely inducing neuronal injury. Montelukast and HAMI 3379 at 0.1-1μmol/L moderately attenuated H2O2-induced neuronal injury (P<0.05). However, both CysLT1R siRNA and CysLT2R shRNA did not significantly affect the responses mentioned above.
CONCLUSIONIn ischemic neuronal injury, montelukast and HAMI 3379 exert a moderate antioxidative effect, and this effect may be receptor-independent.
