The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10284/10013 |
Resumo: | Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC > MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N‑acetyl‑L‑cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury. |
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The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cellsSynthetic cathinonesNephrotoxicityOxidative stressApoptosisAutophagyAntioxidantsSynthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC > MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N‑acetyl‑L‑cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.ElsevierRepositório Institucional da Universidade Fernando PessoaVaz, I.Carvalho, T.Valente, M.J.Castro, A.Araújo, A.M.Bastos, M.L.Carvalho, Márcia2021-07-02T09:32:00Z2020-01-01T00:00:00Z2020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10284/10013eng0378-427410.1016/j.toxlet.2020.05.025metadata 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:RCAAP2022-09-06T02:09:18Zoai:bdigital.ufp.pt:10284/10013Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:46:47.278378Repositório 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 |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
title |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
spellingShingle |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells Vaz, I. Synthetic cathinones Nephrotoxicity Oxidative stress Apoptosis Autophagy Antioxidants |
title_short |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
title_full |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
title_fullStr |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
title_full_unstemmed |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
title_sort |
The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells |
author |
Vaz, I. |
author_facet |
Vaz, I. Carvalho, T. Valente, M.J. Castro, A. Araújo, A.M. Bastos, M.L. Carvalho, Márcia |
author_role |
author |
author2 |
Carvalho, T. Valente, M.J. Castro, A. Araújo, A.M. Bastos, M.L. Carvalho, Márcia |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Institucional da Universidade Fernando Pessoa |
dc.contributor.author.fl_str_mv |
Vaz, I. Carvalho, T. Valente, M.J. Castro, A. Araújo, A.M. Bastos, M.L. Carvalho, Márcia |
dc.subject.por.fl_str_mv |
Synthetic cathinones Nephrotoxicity Oxidative stress Apoptosis Autophagy Antioxidants |
topic |
Synthetic cathinones Nephrotoxicity Oxidative stress Apoptosis Autophagy Antioxidants |
description |
Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC > MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N‑acetyl‑L‑cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-01-01T00:00:00Z 2020-01-01T00:00:00Z 2021-07-02T09:32:00Z |
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/10284/10013 |
url |
http://hdl.handle.net/10284/10013 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0378-4274 10.1016/j.toxlet.2020.05.025 |
dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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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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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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