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Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin

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 an...

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Autores principales: Miranda, Camila Araújo, Beretta, Eduardo Morais, Ferreira, Layra Araújo, da Silva, Emmily Sousa, Coimbra, Beatriz Zimermano, Pereira, Priscila Tartari, Miranda, Raul Ghiraldelli, Dorta, Daniel Junqueira, Rodrigues, Flávia Thomaz Verechia, Mingatto, Fábio Erminio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791245/
https://www.ncbi.nlm.nih.gov/pubmed/36578673
http://dx.doi.org/10.1016/j.toxrep.2022.12.005
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author Miranda, Camila Araújo
Beretta, Eduardo Morais
Ferreira, Layra Araújo
da Silva, Emmily Sousa
Coimbra, Beatriz Zimermano
Pereira, Priscila Tartari
Miranda, Raul Ghiraldelli
Dorta, Daniel Junqueira
Rodrigues, Flávia Thomaz Verechia
Mingatto, Fábio Erminio
author_facet Miranda, Camila Araújo
Beretta, Eduardo Morais
Ferreira, Layra Araújo
da Silva, Emmily Sousa
Coimbra, Beatriz Zimermano
Pereira, Priscila Tartari
Miranda, Raul Ghiraldelli
Dorta, Daniel Junqueira
Rodrigues, Flávia Thomaz Verechia
Mingatto, Fábio Erminio
author_sort Miranda, Camila Araújo
collection PubMed
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.
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spelling pubmed-97912452022-12-27 Role of biotransformation in the diazinon-induced toxicity in HepG2 cells and antioxidant protection by tetrahydrocurcumin Miranda, Camila Araújo Beretta, Eduardo Morais Ferreira, Layra Araújo da Silva, Emmily Sousa Coimbra, Beatriz Zimermano Pereira, Priscila Tartari Miranda, Raul Ghiraldelli Dorta, Daniel Junqueira Rodrigues, Flávia Thomaz Verechia Mingatto, Fábio Erminio Toxicol Rep Article 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. Elsevier 2022-12-12 /pmc/articles/PMC9791245/ /pubmed/36578673 http://dx.doi.org/10.1016/j.toxrep.2022.12.005 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Miranda, Camila Araújo
Beretta, Eduardo Morais
Ferreira, Layra Araújo
da Silva, Emmily Sousa
Coimbra, Beatriz Zimermano
Pereira, Priscila Tartari
Miranda, Raul Ghiraldelli
Dorta, Daniel Junqueira
Rodrigues, Flávia Thomaz Verechia
Mingatto, Fábio Erminio
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791245/
https://www.ncbi.nlm.nih.gov/pubmed/36578673
http://dx.doi.org/10.1016/j.toxrep.2022.12.005
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