Therapeutic potential of N-acetylcysteine in acrylamide acute neurotoxicity in adult zebrafish
| Autor: | Melissa Faria, Manuel Orozco, A I I Mark Arick, Demetrio Raldúa, Eva Prats, Arie Admon, Juliette Bedrossiantz, Shani Ben-Lulu, Cristian Gómez-Canela, Leobardo Manuel Gómez-Oliván, Tamar Ziv, Natàlia Garcia-Reyero, Chuan-Yu Hsu |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Faria, Melissa S. [0000-0003-1451-4427], Prats, Eva [0000-0001-7838-2027], Raldúa, Demetrio [0000-0001-5256-1641], Faria, Melissa S., Prats, Eva, Raldúa, Demetrio |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
medicine.medical_treatment lcsh:Medicine Pharmacology Intestinal absorption Article Acetylcysteine chemistry.chemical_compound In vivo Neurotoxicity syndromes medicine Neurotoxicity Antidote lcsh:Science skin and connective tissue diseases Zebrafish Acrylamide Multidisciplinary ACR lcsh:R Glutathione medicine.disease chemistry Pharmacodynamics lcsh:Q Cysteine medicine.drug |
| Zdroj: | Scientific Reports Digital.CSIC. Repositorio Institucional del CSIC instname Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. This work was supported by the NATO SfP project MD.SFPP 984777 (D.R.) and the Spanish Government (CTM2017-83242-R; D.R.). M.F acknowledges financial support from the Beatriu de Pinós programme (Grant No. 2016 BP 00233) provided by the Secretariat of Universities and Research department of the Ministry for Business and Knowledge, Catalonia Government. Mention of specific products or trade names does not indicate endorsement by the US federal government. |
| Databáze: | OpenAIRE |
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