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Assessing the effects of uracil-based pesticides on hepatic metabolic dysfunctions in low-cost three-dimensional multicellular spheroids

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Autor(es):
de Oliveira, Ana Caroline Pimentel ; Molica, Leticia Ramos ; Moraes, Karen C. M.
Número total de Autores: 3
Tipo de documento: Artigo Científico
Fonte: ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY; v. 121, p. 12-pg., 2025-12-15.
Resumo

Pesticides are used worldwide and cause several pathologies as metabolic dysfunction-associated steatotic liver disease. Steatosis is a mark of the disease beginning; however, the mechanisms by which pesticides act on this dysfunction require further understanding. Thus, this work presents a sensitive and responsive low-cost hepatic multicellular spheroid useful to detail metabolic routes in hepatic dysfunction. Using those spheroids, the effects of pesticides bromacil and terbacil were assessed. Pesticides doses near the acceptable daily intake in Brazil changes energetic, oxidative and the one-carbon metabolism. Moreover, pesticide-specific effects were observed as increased expression of FASN, PPARs, CYP1A1, AHR, DNMTs among others, and changes in the methylation pattern of DNA, RNA and histones. Combined, the results were alarming, considering the long-lasting effects of the evaluated pesticides in agriculture fields. In addition, we can suggest that our spheroid model could be useful for large scale investigation of the effects of pesticides in liver metabolism. (AU)

Processo FAPESP: 22/06302-8 - Efeitos dos contaminantes ambientais terbacil e bromacil no metabolismo lipídico pró-esteatótico em cultura celular hepática e correlações com o metabolismo de uracila e a processos epigenéticos seguido de estudo translacional em Drosophila melanogaster
Beneficiário:Karen Cristiane Martinez de Moraes
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 23/00808-0 - Efeitos de contaminantes ambientais com estrutura análogas a uracila no metabolismo lipídico pró-esteatótico não alcoólico em co-cultura celular e no modelo de cultivo 3D de baixo custo para avaliar suas correlações a processos epigenéticos
Beneficiário:Ana Caroline Pimentel de Oliveira
Modalidade de apoio: Bolsas no Brasil - Mestrado