Utilizad este identificador para citar o enlazar este documento: http://hdl.handle.net/2072/521628

Título:	Therapeutic potential of N-acetylcysteine in acrylamide acute neurotoxicity in adult zebrafish
Autor/a:	Gómez Canela, Cristian; Faria, Melissa; Prats, Eva; Hsu, Chuan-Yu; Arick, Mark A. II; Bedrossiantz, Juliette; Orozco, Manuel; Garcia-Reyero, Natàlia; Ziv, Tamar; Ben-Lulu, Shani; Admon, Arie; Gómez-Oliván, Leonardo Manuel; Raldúa, Demetrio
Otros autores:	Universitat Ramon Llull. IQS
Abstract:	Two essential key events in acrylamide (ACR) acute neurotoxicity are the formation of adducts with nucleophilic sulfhydryl groups on cysteine residues of selected proteins in the synaptic terminals and the depletion of the glutathione (GSx) stores in neural tissue. The use of N-acetylcysteine (NAC) has been recently proposed as a potential antidote against ACR neurotoxicity, as this chemical is not only a well-known precursor of the reduced form of glutathione (GSH), but also is an scavenger of soft electrophiles such as ACR. In this study, the suitability of 0.3 and 0.75 mM NAC to protect against the neurotoxic effect of 0.75 mM ACR has been tested in vivo in adult zebrafish. NAC provided only a mild to negligible protection against the changes induced by ACR in the motor function, behavior, transcriptome and proteome. The permeability of NAC to cross blood-brain barrier (BBB) was assessed, as well as the ACR-scavenging activity and the gamma-glutamyl-cysteine ligase (γ-GCL) and acylase I activities. The results show that ACR not only depletes GSx levels but also inhibits it synthesis from NAC/cysteine, having a dramatic effect over the glutathione system. Moreover, results indicate a very low NAC uptake to the brain, probably by a combination of low BBB permeability and high deacylation of NAC during the intestinal absorption. These results strongly suggest that the use of NAC is not indicated in ACR acute neurotoxicity treatment.
Notas:	Al 2020 es publica una correcció a Scientific Reports. Vol.10, n.1 (2020), 2247 (https://doi.org/10.1038/s41598-020-58946-z)
Fecha de creación:	11-2019
Materias (CDU):	615 - Farmacologia. Terapèutica. Toxicologia. Radiologia
Materia(s):	Neurotoxicologia Química farmacèutica Tecnologia farmacèutica Neurotoxicity syndromes Pharmacodynamics
Derechos:	L'accés als continguts d'aquest document queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons:http://creativecommons.org/licenses/by/4.0/ © L'autor/a
Páginas:	11 p.
Tipo de documento:	Artículo Artículo - Versión publicada
DOI:	https://doi.org/10.1038/s41598-019-53154-w; https://doi.org/10.1038/s41598-020-58946-z
Editor:	Nature Research
Publish at:	Scientific Reports. Vol.9, n.1 (2019), 16467
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