Uracil-derived pesticides and liver health: evaluation of their toxicological effects on adverse signaling pathways (AOPs) in Drosophila melanogaster as an alternative animal research model.

• Grant number: 24/05728-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Karen Cristiane Martinez de Moraes
• Grantee: Victor Hugo Cotinguiba Cantador
• Host Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil

Abstract

Non-alcoholic fatty liver diseases (NAFLDs) are one major public health concern worldwide, because a large proportion of the population is affected by this disease and there are no effective therapies. NAFLD is characterized by the excessive accumulation of lipids in liver cells, which may progress to more serious clinical conditions such as steatohepatitis, cirrhosis and hepatocarcinoma. In addition, NAFLDs present various etiologies, including exposure to environmental contaminants, which have the potential to contaminate the environment, damaging human health and non-target animals. Among these contaminants are those based on the uracil structure, such as bromacil and terbacil, which have been widely used in agriculture. In this context, the Drosophila melanogaster fly has emerged as an important biotechnological tool for studying human diseases, since 70% of the genes related to human diseases are conserved in D. melanogaster. Moreover, the animal presents conserved metabolic pathways when comparing to humans. Therefore, this study aims to evaluate the effects of the pesticides bromacil and terbacil, on energy homeostasis using the fly D. melanogaster as a translational model, considering the presence of analogs structures to the hepatocytes on the animal. To achieve our goals, studies with D. melanogaster submitted to pesticide-contaminate diet will be performed and among them, biochemical analyzes of energetic metabolites, evaluation of gene expression of adverse outcome pathways (AOPs) signaling, the investigation of the integrity and functioning of mitochondria and epigenetics analysis will help to clarify the molecular and cellular effects of the uracil-dependent structed pesticides on organ homeostasis.