N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/224211 |
Resumo: | Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extrasynaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet. Methods: In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish. Results: NAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects. Discussion: NAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD. |
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Benvenutti, RadharaniMarcon, Matheus FelipeReis, Carlos Guilherme RosaNery, Laura RoeslerMiguel, CamilaHerrmann, Ana PaulaVianna, Monica Ryff Moreira RocaPiato, Angelo Luis Stapassoli2021-07-21T04:23:16Z20182167-8359http://hdl.handle.net/10183/224211001077044Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extrasynaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet. Methods: In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish. Results: NAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects. Discussion: NAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.application/pdfengPeerJ. Corte Madera. Vol. 6 (2018), e4957, 17 p.Doença de ParkinsonPeixe-zebraOxidopaminaAcetilcisteínaNeuroproteçãoN-acetylcysteineParkinson’s diseaseZebrafish6-HydroxydopamineN-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvaeEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001077044.pdf.txt001077044.pdf.txtExtracted Texttext/plain47080http://www.lume.ufrgs.br/bitstream/10183/224211/2/001077044.pdf.txt7cef443cacd190b0f182e79610f60721MD52ORIGINAL001077044.pdfTexto completo (inglês)application/pdf1854723http://www.lume.ufrgs.br/bitstream/10183/224211/1/001077044.pdfacd59af3b3fc62d1c44a82508dba6553MD5110183/2242112021-08-18 04:27:40.196278oai:www.lume.ufrgs.br:10183/224211Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-08-18T07:27:40Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
title |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
spellingShingle |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae Benvenutti, Radharani Doença de Parkinson Peixe-zebra Oxidopamina Acetilcisteína Neuroproteção N-acetylcysteine Parkinson’s disease Zebrafish 6-Hydroxydopamine |
title_short |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
title_full |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
title_fullStr |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
title_full_unstemmed |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
title_sort |
N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae |
author |
Benvenutti, Radharani |
author_facet |
Benvenutti, Radharani Marcon, Matheus Felipe Reis, Carlos Guilherme Rosa Nery, Laura Roesler Miguel, Camila Herrmann, Ana Paula Vianna, Monica Ryff Moreira Roca Piato, Angelo Luis Stapassoli |
author_role |
author |
author2 |
Marcon, Matheus Felipe Reis, Carlos Guilherme Rosa Nery, Laura Roesler Miguel, Camila Herrmann, Ana Paula Vianna, Monica Ryff Moreira Roca Piato, Angelo Luis Stapassoli |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Benvenutti, Radharani Marcon, Matheus Felipe Reis, Carlos Guilherme Rosa Nery, Laura Roesler Miguel, Camila Herrmann, Ana Paula Vianna, Monica Ryff Moreira Roca Piato, Angelo Luis Stapassoli |
dc.subject.por.fl_str_mv |
Doença de Parkinson Peixe-zebra Oxidopamina Acetilcisteína Neuroproteção |
topic |
Doença de Parkinson Peixe-zebra Oxidopamina Acetilcisteína Neuroproteção N-acetylcysteine Parkinson’s disease Zebrafish 6-Hydroxydopamine |
dc.subject.eng.fl_str_mv |
N-acetylcysteine Parkinson’s disease Zebrafish 6-Hydroxydopamine |
description |
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extrasynaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet. Methods: In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish. Results: NAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects. Discussion: NAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018 |
dc.date.accessioned.fl_str_mv |
2021-07-21T04:23:16Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/224211 |
dc.identifier.issn.pt_BR.fl_str_mv |
2167-8359 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001077044 |
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http://hdl.handle.net/10183/224211 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
PeerJ. Corte Madera. Vol. 6 (2018), e4957, 17 p. |
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openAccess |
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