The effects of 5-lipoxygenase inhibitor and cysteinyl leukotriene receptor 1 antagonist on 1-methyl-4-phenylpyridine-induced neurotoxicity

被引：0

作者：

ZHANG Xiao-yan ^{[1
,2
]}

LI Chen-tan ^{[1
]}

WANG Yan-fang ^{[1
]}

ZHAO Jian-bo ^{[1
]}

WEI Er-qing ^{[3
]}

ZHANG Li-hui ^{[1
]}

机构：

[1] Department of Pharmacology,Hangzhou Key Laboratory of Medical Neurobiology, School of Medicine,Hangzhou Normal University

[2] Biotherapy Center,The General Hospital of Beijing Military Command

[3] Department of Pharmacology,School of Medicine,Zhejiang University

来源：

中国药理学与毒理学杂志 | 2016年 / 10期

基金：

中国国家自然科学基金;

关键词：

MPP+; neurotoxicity; PC12; cell; 5-lipoxygenase; cysteinyl leukotriene receptor;

D O I：

暂无

中图分类号：

R96 [药理学];

学科分类号：

100602 ; 100706 ;

摘要：

OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.

引用

页码：1022 / 1023

页数：2