Abstract |
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 NFκB 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.
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Authors | Camila Leite Santos, Larissa Daniele Bobermin, Débora Guerini Souza, Bruna Bellaver, Gabriela Bellaver, Bernardo Assein Arús, Diogo Onofre Souza, Carlos-Alberto Gonçalves, André Quincozes-Santos |
Journal | Toxicology in vitro : an international journal published in association with BIBRA
(Toxicol In Vitro)
Vol. 29
Issue 7
Pg. 1350-7
(Oct 2015)
ISSN: 1879-3177 [Electronic] England |
PMID | 26043815
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents
- Antioxidants
- Cytokines
- Nitrites
- S100 Calcium Binding Protein beta Subunit
- S100b protein, rat
- Thioctic Acid
- Ammonia
- Heme Oxygenase (Decyclizing)
- Hmox1 protein, rat
- Extracellular Signal-Regulated MAP Kinases
- Glutathione
- Acetylcysteine
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Topics |
- Acetylcysteine
(pharmacology)
- Ammonia
(toxicity)
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- Antioxidants
(pharmacology)
- Astrocytes
(drug effects, metabolism)
- Cell Line
- Cytokines
(metabolism)
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Glutathione
(metabolism)
- Heme Oxygenase (Decyclizing)
(metabolism)
- Nitrites
(metabolism)
- Rats
- S100 Calcium Binding Protein beta Subunit
(metabolism)
- Signal Transduction
(drug effects)
- Thioctic Acid
(pharmacology)
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