Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.fct.2016.08.020 http://hdl.handle.net/11449/173397 |
Resumo: | Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect. |
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Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesisAntioxidant defenseDiethylnitrosamineMouse hepatocarcinogenesisPreneoplasiaZinc deficiencyZinc supplementationAlthough there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)UNESP – São Paulo State University Botucatu Medical School Department of PathologyUNESP – São Paulo State University Institute of Biosciences of Botucatu Department of MorphologyUNESP – São Paulo State University Institute of Biosciences of Botucatu Department of Chemistry and BiochemistryUSP – University of São Paulo School of Veterinary Medicine and Animal Science Department of PathologyUNESP – São Paulo State University Botucatu Medical School Department of PathologyUNESP – São Paulo State University Institute of Biosciences of Botucatu Department of MorphologyUNESP – São Paulo State University Institute of Biosciences of Botucatu Department of Chemistry and BiochemistryFAPESP: 2012/13004-1FAPESP: 2014/01795-0Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Romualdo, Guilherme Ribeiro [UNESP]Goto, Renata Leme [UNESP]Henrique Fernandes, Ana Angélica [UNESP]Cogliati, BrunoBarbisan, Luis Fernando [UNESP]2018-12-11T17:04:59Z2018-12-11T17:04:59Z2016-10-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article280-289application/pdfhttp://dx.doi.org/10.1016/j.fct.2016.08.020Food and Chemical Toxicology, v. 96, p. 280-289.1873-63510278-6915http://hdl.handle.net/11449/17339710.1016/j.fct.2016.08.0202-s2.0-849834911762-s2.0-84983491176.pdf3278528112652257Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFood and Chemical Toxicology1,144info:eu-repo/semantics/openAccess2024-09-03T13:14:54Zoai:repositorio.unesp.br:11449/173397Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:14:54Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
title |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
spellingShingle |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis Romualdo, Guilherme Ribeiro [UNESP] Antioxidant defense Diethylnitrosamine Mouse hepatocarcinogenesis Preneoplasia Zinc deficiency Zinc supplementation |
title_short |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
title_full |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
title_fullStr |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
title_full_unstemmed |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
title_sort |
Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis |
author |
Romualdo, Guilherme Ribeiro [UNESP] |
author_facet |
Romualdo, Guilherme Ribeiro [UNESP] Goto, Renata Leme [UNESP] Henrique Fernandes, Ana Angélica [UNESP] Cogliati, Bruno Barbisan, Luis Fernando [UNESP] |
author_role |
author |
author2 |
Goto, Renata Leme [UNESP] Henrique Fernandes, Ana Angélica [UNESP] Cogliati, Bruno Barbisan, Luis Fernando [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Romualdo, Guilherme Ribeiro [UNESP] Goto, Renata Leme [UNESP] Henrique Fernandes, Ana Angélica [UNESP] Cogliati, Bruno Barbisan, Luis Fernando [UNESP] |
dc.subject.por.fl_str_mv |
Antioxidant defense Diethylnitrosamine Mouse hepatocarcinogenesis Preneoplasia Zinc deficiency Zinc supplementation |
topic |
Antioxidant defense Diethylnitrosamine Mouse hepatocarcinogenesis Preneoplasia Zinc deficiency Zinc supplementation |
description |
Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-10-01 2018-12-11T17:04:59Z 2018-12-11T17:04:59Z |
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.fct.2016.08.020 Food and Chemical Toxicology, v. 96, p. 280-289. 1873-6351 0278-6915 http://hdl.handle.net/11449/173397 10.1016/j.fct.2016.08.020 2-s2.0-84983491176 2-s2.0-84983491176.pdf 3278528112652257 |
url |
http://dx.doi.org/10.1016/j.fct.2016.08.020 http://hdl.handle.net/11449/173397 |
identifier_str_mv |
Food and Chemical Toxicology, v. 96, p. 280-289. 1873-6351 0278-6915 10.1016/j.fct.2016.08.020 2-s2.0-84983491176 2-s2.0-84983491176.pdf 3278528112652257 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Food and Chemical Toxicology 1,144 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
280-289 application/pdf |
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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1810021377208483840 |