Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells

Detalhes bibliográficos
Autor(a) principal: Soares, Jorge
Data de Publicação: 2020
Outros Autores: Costa, Vera Marisa, Gaspar, Helena, Santos, Susana, Bastos, Maria de Lourdes
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.8/6139
Resumo: Jorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE—Fundo Social Europeu, NORTE2020—Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work was supported by the Applied Molecular Biosciences Unit—UCIBIO through UID/MULTI/04378/2019 support with funding from FCT/MCTES through national funds. Centro de Química Estrutural, BioISI—Biosystems and Integrative Sciences Institute, and MARE—Marine and Environmental Sciences Centre, acknowledges the fnancial support of Fundação para a Ciência e Tecnologia—FCT (UIDB/00100/2020, UID/MULTI/04046/2019 and UIDB/04292/2020, respectively). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the Norma Transitória—DL57/2016/CP1334/CT0006. The authors wish to thank the Laboratório de Polícia Científca da Polícia Judiciária (LPC-PJ) for providing the smartshop product within the scope of the protocol established between LPC-PJ, FCUL, and FFUP.
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spelling Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cellsCathinonesMETHToxicological pathwaysMitochondrial impairmentOxidative stressSH-SY5Y cellsJorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE—Fundo Social Europeu, NORTE2020—Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work was supported by the Applied Molecular Biosciences Unit—UCIBIO through UID/MULTI/04378/2019 support with funding from FCT/MCTES through national funds. Centro de Química Estrutural, BioISI—Biosystems and Integrative Sciences Institute, and MARE—Marine and Environmental Sciences Centre, acknowledges the fnancial support of Fundação para a Ciência e Tecnologia—FCT (UIDB/00100/2020, UID/MULTI/04046/2019 and UIDB/04292/2020, respectively). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the Norma Transitória—DL57/2016/CP1334/CT0006. The authors wish to thank the Laboratório de Polícia Científca da Polícia Judiciária (LPC-PJ) for providing the smartshop product within the scope of the protocol established between LPC-PJ, FCUL, and FFUP.Cathinones (β-keto amphetamines), widely abused in recreational settings, have been shown similar or even worse toxicological profile than classical amphetamines. In the present study, the cytotoxicity of two β-keto amphetamines [3,4-dimethylmethcathinone (3,4-DMMC) and 4-methylmethcathinone (4-MMC)], was evaluated in differentiated dopaminergic SH-SY5Y cells in comparison to methamphetamine (METH). MTT reduction and NR uptake assays revealed that both cathinones and METH induced cytotoxicity in a concentration- and time-dependent manner. Pre-treatment with trolox (antioxidant) partially prevented the cytotoxicity induced by all tested drugs, while N-acetyl-l-cysteine (NAC; antioxidant and glutathione precursor) and GBR 12909 dopamine transporter inhibitor) partially prevented the cytotoxicity induced by cathinones, as evaluated by the MTT reduction assay. Unlike METH, cathinones induced oxidative stress evidenced by the increase on intracellular levels of reactive oxygen species (ROS), and also by the decrease of intracellular glutathione levels. Trolox prevented, partially but significantly, the ROS generation elicited by cathinones, while NAC inhibited it completely. All tested drugs induced mitochondrial dysfunction, since they led to mitochondrial membrane depolarization and to intracellular ATP depletion. Activation of caspase-3, indicative of apoptosis, was seen both for cathinones and METH, and confirmed by annexin V and propidium iodide positive staining. Autophagy was also activated by all drugs tested. Pre-incubation with bafilomycin A1, an inhibitor of the vacuolar H+- ATPase, only protected against the cytotoxicity induced by METH, which indicates dissimilar toxicological pathways for the tested drugs. In conclusion, the mitochondrial impairment and oxidative stress observed for the tested cathinones may be key factors for their neurotoxicity, but different outcome pathways seem to be involved in the adverse effects, when compared to METH.SpringerIC-OnlineSoares, JorgeCosta, Vera MarisaGaspar, HelenaSantos, SusanaBastos, Maria de Lourdes2021-08-23T12:41:05Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.8/6139engSoares J, Costa VM, Gaspar H, Santos S, Bastos ML, Carvalho F, Capela JP. Adverse outcome pathways induced by 3,4-dimethylmethcathinone and 4-methylmethcathinone in differentiated human SH-SY5Y neuronal cells. Arch Toxicol. 2020 Jul;94(7):2481-2503. doi: 10.1007/s00204-020-02761-y.0340-576110.1007/s00204-020-02761-ymetadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-17T15:52:28Zoai:iconline.ipleiria.pt:10400.8/6139Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:49:27.692416Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
title Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
spellingShingle Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
Soares, Jorge
Cathinones
METH
Toxicological pathways
Mitochondrial impairment
Oxidative stress
SH-SY5Y cells
title_short Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
title_full Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
title_fullStr Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
title_full_unstemmed Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
title_sort Adverse outcome pathways induced by 3,4‑dimethylmethcathinone and 4‑methylmethcathinone in differentiated human SH‑SY5Y neuronal cells
author Soares, Jorge
author_facet Soares, Jorge
Costa, Vera Marisa
Gaspar, Helena
Santos, Susana
Bastos, Maria de Lourdes
author_role author
author2 Costa, Vera Marisa
Gaspar, Helena
Santos, Susana
Bastos, Maria de Lourdes
author2_role author
author
author
author
dc.contributor.none.fl_str_mv IC-Online
dc.contributor.author.fl_str_mv Soares, Jorge
Costa, Vera Marisa
Gaspar, Helena
Santos, Susana
Bastos, Maria de Lourdes
dc.subject.por.fl_str_mv Cathinones
METH
Toxicological pathways
Mitochondrial impairment
Oxidative stress
SH-SY5Y cells
topic Cathinones
METH
Toxicological pathways
Mitochondrial impairment
Oxidative stress
SH-SY5Y cells
description Jorge Soares acknowledges University of Porto/Faculty of Medicine University of Porto through FSE—Fundo Social Europeu, NORTE2020—Programa Operacional Regional do Norte for his grant (NORTE-08-5369-FSE-000011). This work was supported by the Applied Molecular Biosciences Unit—UCIBIO through UID/MULTI/04378/2019 support with funding from FCT/MCTES through national funds. Centro de Química Estrutural, BioISI—Biosystems and Integrative Sciences Institute, and MARE—Marine and Environmental Sciences Centre, acknowledges the fnancial support of Fundação para a Ciência e Tecnologia—FCT (UIDB/00100/2020, UID/MULTI/04046/2019 and UIDB/04292/2020, respectively). Vera Marisa Costa acknowledges Fundação da Ciência e Tecnologia (FCT) for her grant (SFRH/BPD/110001/2015) that was funded by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the Norma Transitória—DL57/2016/CP1334/CT0006. The authors wish to thank the Laboratório de Polícia Científca da Polícia Judiciária (LPC-PJ) for providing the smartshop product within the scope of the protocol established between LPC-PJ, FCUL, and FFUP.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2021-08-23T12:41:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.8/6139
url http://hdl.handle.net/10400.8/6139
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Soares J, Costa VM, Gaspar H, Santos S, Bastos ML, Carvalho F, Capela JP. Adverse outcome pathways induced by 3,4-dimethylmethcathinone and 4-methylmethcathinone in differentiated human SH-SY5Y neuronal cells. Arch Toxicol. 2020 Jul;94(7):2481-2503. doi: 10.1007/s00204-020-02761-y.
0340-5761
10.1007/s00204-020-02761-y
dc.rights.driver.fl_str_mv metadata only access
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dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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