Modifying effects of 2,4-D and Glyphosate exposures on gut-liver-adipose tissue axis of diet-induced non-alcoholic fatty liver disease in mice

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorFaculty of Health Sciences-
Autor(es): dc.creatorRomualdo, Guilherme R.-
Autor(es): dc.creatorValente, Letícia Cardoso-
Autor(es): dc.creatorde Souza, Jéssica Luri Hisano-
Autor(es): dc.creatorRodrigues, Josias-
Autor(es): dc.creatorBarbisan, Luís Fernando-
Data de aceite: dc.date.accessioned2025-08-21T22:07:16Z-
Data de disponibilização: dc.date.available2025-08-21T22:07:16Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-11-30-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.ecoenv.2023.115688-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/301337-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/301337-
Descrição: dc.descriptionNonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver steatosis, hypertrophy/inflammation of adipose tissue and deregulation of gut microbiome. Glyphosate and 2,4-D are some of the most applied herbicides worldwide, and their roles in NAFLD have not been investigated. Thus, the present study evaluated whether glyphosate and 2,4-D, in single or mixed exposure, alter WD-induced NAFLD in a mouse model. Male C57Bl/6 mice (n = 10/group) received a fat (30% lard, 0.02% cholesterol), and sucrose-rich diet (20%) and high sugar solution (23.1 and 18.9 g/L of fructose and glucose) for 6 months. Simultaneously, animals received glyphosate (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or their combination (0.05 +0.02 or 5 +2 mg/kg/day) by intragastrical administration (5 ×/week). Doses were based on the Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) levels. Herbicide exposures featured differential responses. WD-induced obesity, hypercholesterolemia, and hyperglycemia remained unaltered. Compared to the group receiving only WD, only the concomitant exposure to WD and 2,4-D (2 mg) enhanced the percentage of mice with moderate/severe hepatic inflammation, CD68 macrophage infiltration, and malondialdehyde levels in the liver. In line, this herbicide modulated immune response- (including Cd4, C8b, Cd28, Cxcr3, Cxcr6) and oxidative stress-related (such as Gsta1, Gsta2, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Nqo1, Gpx2) genes in the hepatic transcriptome analysis. This exposure also enriched pro-inflammatory Deferribacteres phylum in fecal microbiome. In general, the herbicide mixtures did not feature the same effects attributed to 2,4-D isolated exposure. Our findings indicate that 2,4-D, at a dose within the toxicological limits, was able to induce disturbances in mainly at the liver and gut axes involved in NAFLD development in male mice.-
Descrição: dc.descriptionSão Paulo State University (UNESP) Botucatu Medical School Experimental Research Unit (UNIPEX) Multimodel Drug Screening Platform Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) Botucatu Medical School Department of Pathology, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) Biosciences Institute Department of Structural and Functional Biology, SP-
Descrição: dc.descriptionFederal University of Grande Dourados (UFGD) Faculty of Health Sciences, MS-
Descrição: dc.descriptionSão Paulo State University (UNESP) Biosciences Institute Department of Chemical and Biological Sciences, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) Botucatu Medical School Experimental Research Unit (UNIPEX) Multimodel Drug Screening Platform Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) Botucatu Medical School Department of Pathology, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) Biosciences Institute Department of Structural and Functional Biology, SP-
Descrição: dc.descriptionSão Paulo State University (UNESP) Biosciences Institute Department of Chemical and Biological Sciences, SP-
Idioma: dc.languageen-
Relação: dc.relationEcotoxicology and Environmental Safety-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject2,4-D-
Palavras-chave: dc.subjectAdipose tissue-
Palavras-chave: dc.subjectFecal microbiome-
Palavras-chave: dc.subjectGlyphosate-
Palavras-chave: dc.subjectHerbicides-
Palavras-chave: dc.subjectLiver-
Palavras-chave: dc.subjectNonalcoholic fatty liver disease-
Palavras-chave: dc.subjectNonalcoholic steatohepatitis-
Título: dc.titleModifying effects of 2,4-D and Glyphosate exposures on gut-liver-adipose tissue axis of diet-induced non-alcoholic fatty liver disease in mice-
Tipo de arquivo: dc.typelivro digital-
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