VERIFICATION OF THE MANIFESTATION OF THE WARBURG EFFECT IN THE EVOLUTION OF CHAGAS DISEASE

• Grant number: 24/05878-9
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: July 14, 2024
• End date: August 13, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Luciamare Perinetti Alves Martins
• Grantee: Verônica Pedrosa Zandoná
• Supervisor: Marco Aurelio Gouveia Alves
• Host Institution: Faculdade de Medicina de Marília (FAMEMA). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). Marília , SP, Brazil
• Institution abroad: Universidade de Aveiro (UA), Portugal
• Associated to the scholarship: 23/09531-0 - Changes in glucose metabolism in Chagas disease: Warburg effect., BP.IC

Abstract

Chagas disease is an anthropozoonosis endemic in 21 countries in the Americas, whose etiological agent is the protozoan Trypanosoma cruzi (T. cruzi). After infection, the parasites begin metabolic reprogramming with the intention of accelerating intracellular multiplication, opting for a faster energy pathway to obtain ATP, such as the aerobic glycolysis pathway, characterizing the Warburg effect, similar to that described in the process of carcinogenesis. . However, in Chagas disease, it is believed that the effect comes from inflammation developed by the protozoan in the host's cells, which culminates in oxidative stress. It has been suggested that the accumulation of free radicals alters the substrates available for ATP synthesis, which promotes a metabolic shift in oxidative phosphorylation to the aerobic glycolysis pathway producing pyruvate and lactate, even in the presence of high concentrations of oxygen. However, in addition to glucose, branched-chain amino acids (BCAA) and glutamine are believed to be important sources of carbon and nitrogen in the context of rapid cell multiplication in cancer and also in inflammatory processes such as Chagas disease, which would justify the consumptive syndrome that manifests itself in these pathologies. In this way, 60 Swiss mice were infected with 5x104 blood trypomastigote forms of the QM2 strain of T. cruzi, which were divided into three groups of 20 animals for the study at 30, 60 and 120 days post infection. Each group was subdivided into two batches, one batch of 10 animals for the control and the other batch of 10 animals infected by the QM2 strain of T. cruzi. After 10 days of infection, a drop of blood from the tail was observed to verify the success of the infection through fresh examination. At the end of each experimental period, all animals were euthanized and tissues from the heart (atrium) and intestine (colon) were collected, which were stored at -80ºC, later the tissues were freeze-dried for lipid peroxidation tests (TBARS), carbonylation and nitration to detect damage caused by oxidative stress in proteins and lipids. In addition, a metabolic analysis of the tissues will be carried out using Proton Nuclear Magnetic Resonance (1H-NMR), with a particular focus on metabolites of glycolysis and the Krebs cycle such as Pyruvate, Lactate, Alanine, Citrate, among others. Amino acids present such as BCAA (valine, leucine and isoleucine) and Glutamine will also be detected, as well as derivatives of their metabolism. These tasks will be carried out at the Department of Medical Sciences at the University of Aveiro, Portugal. We hope to correlate thebiochemical determinations during the evolution of Chagas disease with the possible manifestation of the Warburg effect in parasitized animals and thereby identifying metabolic targets to mitigate the effects of metabolic reprogramming induced by the infection.