Título:	Investigação do potencial adipogênico dos agrotóxicos ametrina e carbosulfano em cultura de células de mamíferos
Autor(es):	Rodrigues, Kathlen Deruci
Orientador(es):	Amato, Angélica Amorim
Coorientador(es):	Milton, Flora Aparecida
Assunto:	Desreguladores endócrinos Agrotóxicos Receptores nucleares
Data de publicação:	26-Jun-2026
Data de defesa:	3-Ago-2022
Referência:	RODRIGUES, Kathlen Deruci. Investigação do potencial adipogênico dos agrotóxicos ametrina e carbosulfano em cultura de células de mamíferos. 2022. 85 f., il. Dissertação (Mestrado em Ciências da Saúde) — Universidade de Brasília, Brasília, Brasília, 2025.
Abstract:	Brazil is one of the largest consumers of pesticides in the world. Recent studies show that these substances can act as endocrine disruptors, causing adverse effects in the body, including adipogenesis which can lead to weight gain and contribute to the development of obesity. Recent unpublished studies by the research group which I belong identified that the pesticides ametryn and carbosulfan have adipogenic effects on 3T3-L1 cells and that carbosulfan promotes PPARγ activation, a key regulator of adipogenesis. Taking intoconsideration these results and the scarce knowledge about the endocrine disrupting effect of pesticides, studies that investigate this topic are extremely relevant. The aim of this work was to investigate, in mammalian cells culture, other mechanisms that may be related to the adipogenic potential promoted by the pesticides ametryn and carbosulfan. Considering the results previously obtained, a transfection and gene reporter assay using HeLa cells was carried out to evaluate if cysteine 285 was important for the activation of PPARγpromoted by carbosulfan and also to evaluate if the pesticides would promote activation of GRα, PPARα and β, TRα and β and PXR. To evaluate if the lipid accumulation promoted by the pesticides occurred via PPARγ, a cell differentiation assay using 3T3-L1 cells was performed during 15 days. The cells were treated with the concentrations of the pesticides that promoted lipid accumulation, in the presence or absence of T0070907, a specific PPARγantagonist. A RT-qPCR was also performed to compare the expression of inflammatory genes in 3T3-L1 cells treated with ametryn or rosiglitazone, that is a well-known PPARγ agonist with anti-inflammatory properties. As a result, thepresence of the mutation in cysteine 285 abolished the transcriptional activity promoted by carbosulfan suggesting that the cysteine is essential for its activation and that carbosulfan can mimic endogenous ligands. Regarding the receptors investigated, none of the pesticides promoted activation of GRα, PPARα and βand TRα and β. However, carbosulfan promoted PXR activation and can be considered its partial agonist. In the cell differentiation assay with the antagonist was observed that the co-treatment reduced the lipid accumulation promoted by the tested pesticides, suggesting that this accumulation occurs via PPARγ.Regarding the expression of inflammatory genes, ametryn decreased their expression and in its highest concentration, the decrease was similar to that promoted by rosiglitazone but it’s worth mentioning that a higher concentration of ametryn was necessary to promote this effect. The results of this work allow greater knowledge about some pesticides used in Brazil but more studies are needed to understand their effects on complex organisms.
Unidade Acadêmica:	Faculdade de Ciências da Saúde (FS)
Informações adicionais:	Dissertação (mestrado) — Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2025.
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências da Saúde
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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