Changes in glucose metabolism in Chagas disease: Warburg effect.

• Grant number: 23/09531-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Luciamare Perinetti Alves Martins
• Grantee: Verônica Pedrosa Zandoná
• Host Institution: Faculdade de Medicina de Marília (FAMEMA). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). Marília , SP, Brazil
• Associated scholarship(s): 24/05878-9 - VERIFICATION OF THE MANIFESTATION OF THE WARBURG EFFECT IN THE EVOLUTION OF CHAGAS DISEASE, BE.EP.IC

Abstract

Chagas disease is an endemic anthropozoonosis in 21 countries in the Americas with approximately 6 million people affected, whose etiological agent is the protozoan Trypanosoma cruzi (T. cruzi). After infection, the parasites initiate a metabolic reprogramming with the intention of accelerating intracellular multiplication, opting for a faster energy pathway to obtain ATP, the aerobic glycolysis pathway, characterizing the Warburg effect, similar to that described in the carcinogenesis process. However, in Chagas disease, it is believed that the effect comes from the inflammation developed by the protozoan in the host cells, which culminates in oxidative stress, thus, the accumulation of free radicals alters the available substrates for ATP synthesis and deviates the metabolism of the glucose in oxidative phosphorylation to the aerobic glycolysis pathway producing pyruvate and lactate, even in the presence of high concentrations of oxygen. Thus, 60 Swiss mice will be infected with 5x104 blood trypomastigotes of T. cruzi strain QM2. These animals will be divided into three groups of 20 animals for the study at 30, 60 and 120 days post infection. Each group will be subdivided into two lots, one batch of 10 animals for the control and the other batch of 10 animals infected by the QM2 strain of T. cruzi. Weight, blood glucose and ketones will be analyzed weekly. After the end of each study period, all animals will be euthanized in a CO2 chamber and their blood will be collected by cardiac puncture to determine the lipid profile, thiobarbituric acid (TBARS) and C-reactive protein (CRP) concentrations. It is expected to correlate the biochemical determinations during the evolution of Chagas disease with the possible manifestation of the Warburg effect in parasitized animals.