Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.toxrep.2022.12.005 http://hdl.handle.net/11449/249479 |
Resumo: | Diazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indicriminated use may lead to liver damage in animals and humans. This study aimed to evaluate the toxicity of DZN (25–150 µM) on human hepatoblastoma (HepG2) cells after 24 and 48 h of exposure and the role of its biotransformation on the toxicological potential. We also tested the protective effect of tetrahydrocurcumin (THC), an antioxidant agent, in the DZN-induced citotoxicity. DZN caused cytotoxicity in the HepG2 cells, inhibiting cell proliferation and reducing cell viability in a dose- and time-dependent manner. The pre-incubation of HepG2 cells with chemical inducers of cytochrome P450 monooxygenase 3-methylcholanthrene and phenobarbital resulted in a further decrease of cell viability associated with DZN exposure. In addition, the metabolite diazoxon was more toxic than DZN. Our results also revealed that THC alleviated DZN-induced cytotoxicity and reactive oxygen and nitrogen species (RONS) generation in HepG2 cells. In conclusion, our data provide novel insights into the involvement of biotransformation in the mechanisms of DZN-induced cytotoxicity and suggest that amelioration of RONS accumulation might be involved in the protective effect of THC on DZN-induced liver injury. |
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Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcuminAntioxidantsHepG2 cell lineOrganophosphorus insecticidesRONSToxicityDiazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indicriminated use may lead to liver damage in animals and humans. This study aimed to evaluate the toxicity of DZN (25–150 µM) on human hepatoblastoma (HepG2) cells after 24 and 48 h of exposure and the role of its biotransformation on the toxicological potential. We also tested the protective effect of tetrahydrocurcumin (THC), an antioxidant agent, in the DZN-induced citotoxicity. DZN caused cytotoxicity in the HepG2 cells, inhibiting cell proliferation and reducing cell viability in a dose- and time-dependent manner. The pre-incubation of HepG2 cells with chemical inducers of cytochrome P450 monooxygenase 3-methylcholanthrene and phenobarbital resulted in a further decrease of cell viability associated with DZN exposure. In addition, the metabolite diazoxon was more toxic than DZN. Our results also revealed that THC alleviated DZN-induced cytotoxicity and reactive oxygen and nitrogen species (RONS) generation in HepG2 cells. In conclusion, our data provide novel insights into the involvement of biotransformation in the mechanisms of DZN-induced cytotoxicity and suggest that amelioration of RONS accumulation might be involved in the protective effect of THC on DZN-induced liver injury.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Animal Science College of Agricultural and Technological Sciences São Paulo State University (Unesp), SPMedical School Unifadra Faculdades de Dracena, SPDepartment of Chemistry Faculty of Philosophy Sciences and Letters of Ribeirão Preto University of São Paulo, SPDepartment of Animal Science College of Agricultural and Technological Sciences São Paulo State University (Unesp), SPFAPESP: 2018/22002-9FAPESP: 2019/12497-3Universidade Estadual Paulista (UNESP)Faculdades de DracenaUniversidade de São Paulo (USP)Miranda, Camila Araújo [UNESP]Beretta, Eduardo Morais [UNESP]Ferreira, Layra Araújo [UNESP]da Silva, Emmily SousaCoimbra, Beatriz ZimermanoPereira, Priscila TartariMiranda, Raul GhiraldelliDorta, Daniel JunqueiraRodrigues, Flávia Thomaz Verechia [UNESP]Mingatto, Fábio Erminio [UNESP]2023-07-29T15:42:31Z2023-07-29T15:42:31Z2023-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article32-39http://dx.doi.org/10.1016/j.toxrep.2022.12.005Toxicology Reports, v. 10, p. 32-39.2214-7500http://hdl.handle.net/11449/24947910.1016/j.toxrep.2022.12.0052-s2.0-85144068222Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxicology Reportsinfo:eu-repo/semantics/openAccess2024-05-07T13:47:22Zoai:repositorio.unesp.br:11449/249479Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:51:39.196281Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
title |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
spellingShingle |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin Miranda, Camila Araújo [UNESP] Antioxidants HepG2 cell line Organophosphorus insecticides RONS Toxicity |
title_short |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
title_full |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
title_fullStr |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
title_full_unstemmed |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
title_sort |
Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin |
author |
Miranda, Camila Araújo [UNESP] |
author_facet |
Miranda, Camila Araújo [UNESP] Beretta, Eduardo Morais [UNESP] Ferreira, Layra Araújo [UNESP] da Silva, Emmily Sousa Coimbra, Beatriz Zimermano Pereira, Priscila Tartari Miranda, Raul Ghiraldelli Dorta, Daniel Junqueira Rodrigues, Flávia Thomaz Verechia [UNESP] Mingatto, Fábio Erminio [UNESP] |
author_role |
author |
author2 |
Beretta, Eduardo Morais [UNESP] Ferreira, Layra Araújo [UNESP] da Silva, Emmily Sousa Coimbra, Beatriz Zimermano Pereira, Priscila Tartari Miranda, Raul Ghiraldelli Dorta, Daniel Junqueira Rodrigues, Flávia Thomaz Verechia [UNESP] Mingatto, Fábio Erminio [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Faculdades de Dracena Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Miranda, Camila Araújo [UNESP] Beretta, Eduardo Morais [UNESP] Ferreira, Layra Araújo [UNESP] da Silva, Emmily Sousa Coimbra, Beatriz Zimermano Pereira, Priscila Tartari Miranda, Raul Ghiraldelli Dorta, Daniel Junqueira Rodrigues, Flávia Thomaz Verechia [UNESP] Mingatto, Fábio Erminio [UNESP] |
dc.subject.por.fl_str_mv |
Antioxidants HepG2 cell line Organophosphorus insecticides RONS Toxicity |
topic |
Antioxidants HepG2 cell line Organophosphorus insecticides RONS Toxicity |
description |
Diazinon (DZN) is an insecticide extensively used to control pests in crops and animals. However, its indicriminated use may lead to liver damage in animals and humans. This study aimed to evaluate the toxicity of DZN (25–150 µM) on human hepatoblastoma (HepG2) cells after 24 and 48 h of exposure and the role of its biotransformation on the toxicological potential. We also tested the protective effect of tetrahydrocurcumin (THC), an antioxidant agent, in the DZN-induced citotoxicity. DZN caused cytotoxicity in the HepG2 cells, inhibiting cell proliferation and reducing cell viability in a dose- and time-dependent manner. The pre-incubation of HepG2 cells with chemical inducers of cytochrome P450 monooxygenase 3-methylcholanthrene and phenobarbital resulted in a further decrease of cell viability associated with DZN exposure. In addition, the metabolite diazoxon was more toxic than DZN. Our results also revealed that THC alleviated DZN-induced cytotoxicity and reactive oxygen and nitrogen species (RONS) generation in HepG2 cells. In conclusion, our data provide novel insights into the involvement of biotransformation in the mechanisms of DZN-induced cytotoxicity and suggest that amelioration of RONS accumulation might be involved in the protective effect of THC on DZN-induced liver injury. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T15:42:31Z 2023-07-29T15:42:31Z 2023-01-01 |
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/10.1016/j.toxrep.2022.12.005 Toxicology Reports, v. 10, p. 32-39. 2214-7500 http://hdl.handle.net/11449/249479 10.1016/j.toxrep.2022.12.005 2-s2.0-85144068222 |
url |
http://dx.doi.org/10.1016/j.toxrep.2022.12.005 http://hdl.handle.net/11449/249479 |
identifier_str_mv |
Toxicology Reports, v. 10, p. 32-39. 2214-7500 10.1016/j.toxrep.2022.12.005 2-s2.0-85144068222 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Toxicology Reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
32-39 |
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 |
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1808128711062454272 |