title: Resveratrol prevents ammonia toxicity in astroglial cells.
abstract: Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO) production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS). Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS), GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB) are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox) were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity.
authors.affiliation: Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Larissa Daniele
authors.initials: LD
authors.lastname: Bobermin
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Guerra
authors.forename: Marina Concli
authors.initials: MC
authors.lastname: Leite
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
mesh_terms: D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase; D000077185:Resveratrol