Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis

Autor: Bruno Cogliati, Luis Fernando Barbisan, Guilherme Ribeiro Romualdo, Ana Angélica Henrique Fernandes, Renata Leme Goto
Přispěvatelé: Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP)
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Antioxidant
medicine.medical_treatment
ZINCO
Apoptosis
Toxicology
medicine.disease_cause
Antioxidants
Mice
chemistry.chemical_compound
Liver Neoplasms
Experimental
0302 clinical medicine
Antioxidant defense
Diethylnitrosamine
Mice
Inbred BALB C
Zinc deficiency
Organ Size
General Medicine
Zinc
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Female
Preneoplasia
Alkylating Agents
medicine.medical_specialty
Carcinoma
Hepatocellular
chemistry.chemical_element
Biology
Dietary zinc deficiency
03 medical and health sciences
Mouse hepatocarcinogenesis
Internal medicine
medicine
Animals
Humans
Zinc supplementation
Cell Proliferation
Cell growth
Glutathione
medicine.disease
Diet
030104 developmental biology
Endocrinology
Animals
Newborn
chemistry
Dietary Supplements
Immunology
Tumor Suppressor Protein p53
Genotoxicity
DNA Damage
Food Science
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 0278-6915
DOI: 10.1016/j.fct.2016.08.020
Popis: Made available in DSpace on 2018-12-11T17:04:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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. UNESP – São Paulo State University Botucatu Medical School Department of Pathology UNESP – São Paulo State University Institute of Biosciences of Botucatu Department of Morphology UNESP – São Paulo State University Institute of Biosciences of Botucatu Department of Chemistry and Biochemistry USP – University of São Paulo School of Veterinary Medicine and Animal Science Department of Pathology UNESP – São Paulo State University Botucatu Medical School Department of Pathology UNESP – São Paulo State University Institute of Biosciences of Botucatu Department of Morphology UNESP – São Paulo State University Institute of Biosciences of Botucatu Department of Chemistry and Biochemistry FAPESP: 2012/13004-1 FAPESP: 2014/01795-0
Databáze: OpenAIRE
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