Investigation of epigenetic modulation promoted by the herbicide glyphosate with or without co-exposure to green tea and guarana extracts - metabolic, inflammatory and endocrine outcomes in in vitro cell models.

• Grant number: 24/08979-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Rosemari Otton
• Grantee: Rosemari Otton
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Associated researchers: Anaysa Paola Bolin ; Guilherme Ribeiro Romualdo

Abstract

Glyphosate is an organophosphate herbicide widely used around the world due to its low cost, strong systemic conductivity, and broad herbicidal spectrum. Glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in the shikimate pathway, disrupting the synthesis of aromatic amino acids in plants. Glyphosate-based herbicides (GBHs) like Roundup not only destroy the ecosystem but also accumulate in animals through bioaccumulation and spread along the food chain, producing toxic effects on non-target organisms. Although regulatory agencies have deemed glyphosate safe when used according to recommended guidelines, controversies have arisen over its potential health and environmental impacts, leading to ongoing debate and research. Glyphosate has been reported to have a potential endocrine-disrupting effect, raising concerns about its impact on the hormonal systems of animals and humans, as it interferes with the endocrine system, interrupting hormonal signaling pathways, particularly the estrogen and androgen pathways. There is a time frame between industrialization, large-scale agricultural production, and the emergence of current metabolic and degenerative diseases. The extent to which pesticides and their metabolites, increasingly present in quantity and frequency in fresh and ultra-processed foods, are implicated in the increased incidence of metabolic diseases in the population, is still a topic that has been little studied and discussed. Based on the above, this proposal has as its main pillar the investigation of GBH Roundup's endocrine, metabolic, and inflammatory disruptive effect on adipocytes, hepatocytes, and immune cells (lymphocytes and human peripheral neutrophils) in association with its epigenetic repercussions. To this end, as a novel contribution to the area, we intend to perform both miRNAseq and RNAseq, investigating epigenetic networks modulated by glyphosate as well as the main DNA methylation pathways and expression of enzymes involved in these pathways and its correlation with metabolic, inflammatory and endocrine outcomes. In parallel, we intend to investigate whether green tea and guarana extracts can positively modulate the mentioned parameters, using co-exposure, co-culture, and conditioned medium experiments, revealing a possible reprogramming of cells to a more positive phenotype, to be considered to be less inflammatory and metabolically closer to those of cells in the control group. Such results could serve as a scientific basis for future studies on the human population, helping to increase the area of knowledge about multiple exposures to harmful agents and compounds notably beneficial to human health, facilitating the search for forms of prevention and treatment. (AU)