Lipoic acid and N-acetylcysteine prevent ammonia-induced inflammatory response in C6 astroglial cells: The putative role of ERK and HO1 signaling pathways

被引：20

作者：

Santos, Camila Leite ^{[1
]}

Bobermin, Larissa Daniele ^{[1
]}

Souza, Debora Guerini ^{[1
]}

Bellaver, Bruna ^{[1
]}

Bellaver, Gabriela ^{[1
]}

Arus, Bernardo Assein ^{[1
]}

Souza, Diogo Onofre ^{[1
]}

Goncalves, Carlos-Alberto ^{[1
]}

Quincozes-Santos, Andre ^{[1
]}

机构：

[1] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Programa Posgrad Ciencias Biol Bioquim, Dept Bioquim, BR-90035003 Porto Alegre, RS, Brazil

来源：

TOXICOLOGY IN VITRO | 2015年 / 29卷 / 07期

关键词：

Ammonia cytotoxicity; LA; NAC; Inflammatory response; ERK; HO1; GLUTAMINE-SYNTHETASE ACTIVITY; CENTRAL-NERVOUS-SYSTEM; KAPPA-B ACTIVATION; OXIDATIVE STRESS; ACETYL-CYSTEINE; ENERGY-METABOLISM; NITRIC-OXIDE; ASTROCYTES; BRAIN; INHIBITION;

D O I：

10.1016/j.tiv.2015.05.023

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Hyperammonemia induces significant changes in the central nervous system (CNS) in direct association with astroglial functions, such as oxidative damage, glutamatergic excitotoxicity, and impaired glutamine synthetase (GS) activity and pro-inflammatory cytokine release. Classically, lipoic acid (LA) and N-acetylcysteine (NAC) exhibit antioxidant and anti-inflammatory activities by increasing glutathione (GSH) biosynthesis and decreasing pro-inflammatory mediator levels in glial cells. Thus, we evaluated the protective effects of LA and NAC against ammonia cytotoxicity in C6 astroglial cells. Ammonia decreased GSH levels and increased cytokine release and NEKB transcriptional activation. LA and NAC prevented these effects by the modulation of ERK and HO1 pathways. Taken together, these observations show that LA and NAC prevent the ammonia-induced inflammatory response. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：1350 / 1357

页数：8

共 76 条

[41] Supplementation of N-acetylcysteine normalizes lipopolysaccharide-induced nuclear factor κB activation and proinflammatory cytokine production during early rehabilitation of protein malnourished mice [J].