Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells

In the environment, or during mammalian metabolism, the diuron herbicide (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is transformed mainly into 3-(3,4-dichlorophenyl)-1-methylurea (DCPMU) and 3,4-dichloroaniline (DCA). Previous research suggests that such substances are toxic to the urothelium of Wist...

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Autores: Lima, Thania Rios Rossi [UNESP], Kohori, Natalia Akemi [UNESP], de Camargo, João Lauro Viana [UNESP], da Silva, Carla Adriene [UNESP], Pereira, Lilian Cristina [UNESP]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/301050
Acceso en línea:http://dx.doi.org/10.1080/15376516.2023.2250430
https://hdl.handle.net/11449/301050
Access Level:acceso abierto
Palabra clave:1T1 cell culture
diuron and metabolites
mitochondrial pathways
Mitotoxicants
toxicodynamics
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spelling Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells1T1 cell culturediuron and metabolitesmitochondrial pathwaysMitotoxicantstoxicodynamicsIn the environment, or during mammalian metabolism, the diuron herbicide (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is transformed mainly into 3-(3,4-dichlorophenyl)-1-methylurea (DCPMU) and 3,4-dichloroaniline (DCA). Previous research suggests that such substances are toxic to the urothelium of Wistar rats where, under specific exposure conditions, they may induce urothelial cell degeneration, necrosis, hyperplasia, and eventually tumors. However, the intimate mechanisms of action associated with such chemical toxicity are not fully understood. In this context, the purpose of the current in vitro study was to analyze the underlying mechanisms involved in the urothelial toxicity of those chemicals, addressing cell death and the possible role of mitochondrial dysfunction. Thus, human 1T1 urothelial cells were exposed to six different concentrations of diuron, DCA, and DCPMU, ranging from 0.5 to 500 µM. The results showed that tested chemicals induced oxidative stress and mitochondrial damage, cell cycle instability, and cell death, which were more expressive at the higher concentrations of the metabolites. These data corroborate previous studies from this laboratory and, collectively, suggest mitochondrial dysfunction as an initiating event triggering urothelial cell degeneration and death.São Paulo State University (UNESP) Medical SchoolCenter for Evaluation of Environmental Impact on Human Health (TOXICAM) UNESP Medical SchoolSão Paulo State University (UNESP) School of AgricultureSão Paulo State University (UNESP) Medical SchoolCenter for Evaluation of Environmental Impact on Human Health (TOXICAM) UNESP Medical SchoolSão Paulo State University (UNESP) School of AgricultureUniversidade Estadual Paulista (UNESP)2025-04-29T18:57:07Z2024-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article32-45http://dx.doi.org/10.1080/15376516.2023.2250430Toxicology Mechanisms and Methods, v. 34, n. 1, p. 32-45, 2024.1537-65241537-6516https://hdl.handle.net/11449/30105010.1080/15376516.2023.22504302-s2.0-85169822100Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxicology Mechanisms and Methodsinfo:eu-repo/semantics/openAccessLima, Thania Rios Rossi [UNESP]Kohori, Natalia Akemi [UNESP]de Camargo, João Lauro Viana [UNESP]da Silva, Carla Adriene [UNESP]Pereira, Lilian Cristina [UNESP]2025-10-16T08:04:28Zoai:repositorio.unesp.br:11449/301050Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462025-10-16T08:04:28Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
title Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
spellingShingle Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
Lima, Thania Rios Rossi [UNESP]
1T1 cell culture
diuron and metabolites
mitochondrial pathways
Mitotoxicants
toxicodynamics
title_short Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
title_full Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
title_fullStr Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
title_full_unstemmed Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
title_sort Diuron and its metabolites induce mitochondrial dysfunction-mediated cytotoxicity in urothelial cells
dc.creator.none.fl_str_mv Lima, Thania Rios Rossi [UNESP]
Kohori, Natalia Akemi [UNESP]
de Camargo, João Lauro Viana [UNESP]
da Silva, Carla Adriene [UNESP]
Pereira, Lilian Cristina [UNESP]
author Lima, Thania Rios Rossi [UNESP]
author_facet Lima, Thania Rios Rossi [UNESP]
Kohori, Natalia Akemi [UNESP]
de Camargo, João Lauro Viana [UNESP]
da Silva, Carla Adriene [UNESP]
Pereira, Lilian Cristina [UNESP]
author_role author
author2 Kohori, Natalia Akemi [UNESP]
de Camargo, João Lauro Viana [UNESP]
da Silva, Carla Adriene [UNESP]
Pereira, Lilian Cristina [UNESP]
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
dc.subject.por.fl_str_mv 1T1 cell culture
diuron and metabolites
mitochondrial pathways
Mitotoxicants
toxicodynamics
topic 1T1 cell culture
diuron and metabolites
mitochondrial pathways
Mitotoxicants
toxicodynamics
description In the environment, or during mammalian metabolism, the diuron herbicide (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is transformed mainly into 3-(3,4-dichlorophenyl)-1-methylurea (DCPMU) and 3,4-dichloroaniline (DCA). Previous research suggests that such substances are toxic to the urothelium of Wistar rats where, under specific exposure conditions, they may induce urothelial cell degeneration, necrosis, hyperplasia, and eventually tumors. However, the intimate mechanisms of action associated with such chemical toxicity are not fully understood. In this context, the purpose of the current in vitro study was to analyze the underlying mechanisms involved in the urothelial toxicity of those chemicals, addressing cell death and the possible role of mitochondrial dysfunction. Thus, human 1T1 urothelial cells were exposed to six different concentrations of diuron, DCA, and DCPMU, ranging from 0.5 to 500 µM. The results showed that tested chemicals induced oxidative stress and mitochondrial damage, cell cycle instability, and cell death, which were more expressive at the higher concentrations of the metabolites. These data corroborate previous studies from this laboratory and, collectively, suggest mitochondrial dysfunction as an initiating event triggering urothelial cell degeneration and death.
publishDate 2024
dc.date.none.fl_str_mv 2024-01-01
2025-04-29T18:57:07Z
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://dx.doi.org/10.1080/15376516.2023.2250430
Toxicology Mechanisms and Methods, v. 34, n. 1, p. 32-45, 2024.
1537-6524
1537-6516
https://hdl.handle.net/11449/301050
10.1080/15376516.2023.2250430
2-s2.0-85169822100
url http://dx.doi.org/10.1080/15376516.2023.2250430
https://hdl.handle.net/11449/301050
identifier_str_mv Toxicology Mechanisms and Methods, v. 34, n. 1, p. 32-45, 2024.
1537-6524
1537-6516
10.1080/15376516.2023.2250430
2-s2.0-85169822100
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicology Mechanisms and Methods
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 32-45
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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score 15,198674

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