Xenobiotics and the pro-steatotic process in cell culture: a metabolic and molecular study

• Grant number: 23/08538-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Karen Cristiane Martinez de Moraes
• Grantee: Lívia Helena Carmona Durante
• Host Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a global public health concern. It is a pathology characterized by the accumulation of fat in the liver, which may progress to more severe clinical conditions. The etiologies of NAFLD are diverse, including exposure to xenobiotics, such as pesticides and pharmaceutical drugs. These compounds have the potential to contaminate the environment, harming the health of animals and humans. Therefore, this proposal aims to investigate the effects of the pesticide Lenacil, and the fármacos, 5-Fluorouracil, both with molecular structures based on the structure of uracil. In addition to the risks of direct handling of these substances, there is the risk of environmental contamination, harming animals, and humans. Because the structure analogous to uracil, drugs and pesticides can disrupt the homeostasis of pyrimidines by being incorporated into the structure of RNA and DNA, causing damage to liver health, through different biochemical pathways. In this context, we propose to evaluate these xenobiotics in a comparative way in a cellular model of coculture of liver cells, to clarify the metabolic and molecular aspects that cause changes in mitochondrial health and in the generation of oxidative stress, related to hepatotoxicity and induction of prosteatotic process. To this end, cell cultures and analyses of cell viability, biochemical analyses related to energy metabolism, evaluation of gene expression and assays related to the integrity and functionality of mitochondria will be performed. The elucidation of the mechanisms of these Xenobiotics is fundamental for their safe use in order to avoid harmful effects on health and the environment.