Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorRomualdo, Guilherme Ribeiro-
Autor(es): dc.creatorPrata, Gabriel Bacil-
Autor(es): dc.creatorda Silva, Tereza Cristina-
Autor(es): dc.creatorFernandes, Ana Angélica Henrique-
Autor(es): dc.creatorMoreno, Fernando Salvador-
Autor(es): dc.creatorCogliati, Bruno-
Autor(es): dc.creatorBarbisan, Luís Fernando-
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Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionCNPq: #140251/2016-2-
Descrição: dc.descriptionProcesso FAPESP: #2016/ 12015-0-
Descrição: dc.descriptionProcesso FAPESP: #2016/14420-0-
Descrição: dc.descriptionHepatocellular carcinoma causes ~10% of all cancer-related deaths worldwide, usually emerging in a background of liver fibrosis/cirrhosis (70%-90% of cases). Chemically-induced mouse models for fibrosis-associated hepatocarcinogenesis are widely-applied, resembling the corresponding human disease. Nonetheless, a long time is necessary for the development of preneoplastic/neoplastic lesions. Thus, we proposed an early fibrosis-associated hepatocarcinogenesis model for male and female mice separately, focusing on reducing the experimental time for preneoplastic/neoplastic lesions development and establishing standard models for both sexes. Then, two-week old susceptible C3H/HeJ male and female mice (n = 8 animals/sex/group) received a single dose of diethylnitrosamine (DEN, 10 or 50 mg/Kg). During 2 months, mice received 3 weekly doses of carbon tetrachloride (CCl4, 10% corn oil solution, 0.25 to 1.50 μL/g b.wt.) and they were euthanized at week 17. DEN/CCl4 protocols for males and females displayed clear liver fibrosis, featuring collagen accumulation and hepatic stellate cell activation (α-SMA). In addition, liver from males displayed increased CD68+ macrophage number, COX-2 protein expression and IL-6 levels. The DEN/CCl4 models in both sexes impaired antioxidant defense as well as enhanced hepatocyte proliferation and apoptosis. Moreover, DEN/CCl4-treated male and female developed multiple preneoplastic altered hepatocyte foci and hepatocellular adenomas. As expected, the models showed clear male bias. Therefore, we established standard and suitable fibrosis-associated hepatocarcinogenesis models for male and female mice, shortening the experimental time for the development of hepatocellular preneoplastic/neoplastic lesions in comparison to other classical models.-
Idioma: dc.languageen-
Relação: dc.relationPLoS ONE-
Relação: dc.relation1,164-
Direitos: dc.rightsopenAccess-
Título: dc.titleFibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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