Use of omics approaches (proteomics and metabolomics) to elucidate the toxicity mechanisms of ametrine and clomazone, isolated or combined, in HepG2 cells and Zebrafish

• Grant number: 22/05645-9
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2023
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Fábio Erminio Mingatto
• Grantee: Fábio Erminio Mingatto
• Host Institution: Faculdade de Ciências Agrárias e Tecnológicas. Universidade Estadual Paulista (UNESP). Campus de Dracena. Dracena , SP, Brazil
• Associated researchers: Carlos Manuel Marques Palmeira ; Daniel Junqueira Dorta ; Danielle Palma de Oliveira ; Ernani Pinto Junior ; Lilian Cristina Pereira
• Associated scholarship(s): 24/04954-3 - Effects of the herbicides ametrine and clomazone, alone or combined, on parameters related to MPT, calcium homeostasis and oxidative stress in mitochondria isolated from rat liver and cell death and omics analyzes in HepG2 cells, BP.TT

Abstract

Ametrine (AMT) and clomazone (CLZ) are two herbicides widely used in agriculture. Both are found in food and water samples and there are reports in the literature that these compounds are toxic to humans and animals. Studies have shown that exposure to herbicides can cause metabolic disorders and oxidative damage in various tissues, including the liver. Data on the effects of mixing AMT and CLZ are still scarce. Preliminary data obtained in our laboratory using isolated rat liver mitochondria suggest that AMT inhibits the respiratory chain, leading to reduced ATP synthesis. Furthermore, studies in zebrafish embryos showed that AMT induces oxidative stress and alters the protein profile of these animals, including proteins related to oxidative phosphorylation, while a metabolomic analysis in fungi indicated that AMT promoted changes in carbon and nitrogen metabolism. Regarding CLZ, studies with zebrafish embryos showed that the herbicide affected several parameters of embryonic development, leading to an increase in the embryo mortality rate, however, the biochemical mechanisms involved have not yet been studied in depth. Therefore, based on the previous results obtained in our laboratory and the data found in the literature, we propose the development of two complementary studies: (I) investigation of the metabolic alterations caused by the herbicides AMT and CLZ, isolated or combined, through approaches " omics" (proteomics and metabolomics) in a study model "in vitro" using HepG2 cells and "in vivo" using zebrafish; (II) "in vitro" study using mitochondria isolated from rat liver and HepG2 cells in order to better characterize the metabolic alterations observed in the initial study. (AU)