CARDIOTOXICITY INDUCED BY THE PESTICIDE TEBUCONAZOLE IN MICE: FROM CONCEPTION TO ADULT LIFE

• Grant number: 21/15122-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2022
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Danilo Roman Campos
• Grantee: Leisiane Pereira Marques
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/05584-7 - Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil, AP.JP2

Abstract

Pesticides are important components in the control of pests that affect plants, animals and humans. The intensive use of these chemicals, however, has implications for the ecosystem and human health. Due to its wide use and repeated applications, residues of fungicides, including tebuconazole (TEB), are part of the wide spectrum of pesticides found in water and food consumed by Brazilians. TEB is a triazole fungicide, recognized for inhibiting ergosterol biosynthesis and its high physicochemical stability ensures its persistence in the environment, where it can act on non-target species, including humans. It is described that exposure to TEB can result in toxicity to various organs, such as the liver, kidneys, brain and heart. Furthermore, maternal exposure to TEB during pregnancy results in problems with fetal development. Knowing that women of childbearing age are at increased risk of dietary exposure to TEB and that maternal exposure to environmental toxins is associated with a greater predisposition to develop heart problems in their children after birth and adulthood, we aim to investigate the effects cardiotoxic effects of tebuconazole in offspring mice after maternal exposure to the fungicide during pregnancy and lactation, specifically, assess the effects of TEB on: (1) markers of cardiac injury and lipid profile, through biochemical analyzes of sérum samples; (2) cardiac tissue remodeling, through morphometric and histopathological analysis of the heart; (3) oxidative stress and (4) cardiac electrical activity, through electrocardiography techniques (in vivo and ex vivo) and in vitro through the patch-clamp technique applied to isolated cardiomyocytes. At the end, we will be able to determinate if maternal exposure to TEB is able to induce heart remodeling to the offspring, which may impact the use of TEB in agriculture.

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TEIXEIRA-FONSECA, JORGE LUCAS; SANTOS-MIRANDA, ARTUR; MARQUES, IVAN LOBO SOUSA; MARQUES, LEISIANE PEREIRA; ALCANTARA, FABIANA; CONCEICAO, MICHAEL RAMON DE LIMA; SOUZA, DIEGO SANTOS; GONDIM, ANTONIO NEI SANTANA; ROMAN-CAMPOS, DANILO. Eugenol delays the onset of ouabain-induced ventricular cardiac arrhythmias in guinea pigs. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. N/A, p. 11-pg., 2023-09-19. (21/15122-0, 20/14635-1, 21/05584-7, 19/18918-0)

MARQUES, LEISIANE P.; JOVIANO-SANTOS, JULLIANE, V; SOUZA, DIEGO S.; SANTOS-MIRANDA, A.; ROMAN-CAMPOS, D.. Cardiotoxicity of pyrethroids: molecular mechanisms and therapeutic options for acute and long-term toxicity. BIOCHEMICAL SOCIETY TRANSACTIONS, v. N/A, p. 15-pg., 2022-10-31. (21/15122-0, 21/05584-7, 19/18918-0)

MARQUES, LEISIANE PEREIRA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE VASCONCELOS; TEIXEIRA-FONSECA, JORGE LUCAS; ALCANTARA, FABIANA DA SILVA; SARMENTO, JAQUELINE OLIVEIRA; ROMAN-CAMPOS, DANILO. The fungicide tebuconazole modulates the sodium current of human Na_V1.5 channels expressed in HEK293 cells. Food and Chemical Toxicology, v. 180, p. 12-pg., 2023-08-30. (21/15122-0, 20/14635-1, 21/05584-7)

TEIXEIRA-FONSECA, JORGE LUCAS; JOVIANO-SANTOS, JULLIANE V.; BESERRA, SAMUEL SANTOS; CONCEICAO, MICHAEL RAMON DE LIMA; LEAL-SILVA, POLYANA; MARQUES, LEISIANE PEREIRA; SOUZA, DIEGO SANTOS; ROMAN-CAMPOS, DANILO. Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. N/A, p. 14-pg., 2023-06-20. (19/21304-4, 19/18918-0, 21/15122-0, 20/14635-1, 21/05584-7)

TEIXEIRA-FONSECA, JORGE LUCAS; SOUZA, DIEGO SANTOS; CONCEICAO, MICHAEL RAMON DE LIMA; MARQUES, LEISIANE PEREIRA; DURCO, AIMEE OBOLARI; DA SILVA, POLYANA LEAL; JOVIANO-SANTOS, JULLIANE V.; SANTOS-MIRANDA, ARTUR; ROMAN-CAMPOS, DANILO. In vivo tebuconazole administration impairs heart electrical function and facilitates the occurrence of dobutamine-induced arrhythmias: involvement of reactive oxygen species. Food and Chemical Toxicology, v. 187, p. 12-pg., 2024-04-04. (22/14133-1, 21/05584-7, 20/14635-1, 21/15122-0, 23/11912-2)

DE CONCEICAO, MICHAEL RAMON LIMA; TEIXEIRA-FONSECA, JORGE LUCAS; MARQUES, LEISIANE PEREIRA; SOUZA, DIEGO SANTOS; ROMAN-CAMPOS, DANILO. Interaction of the antiarrhythmic drug Amiodarone with the sodium channel Nav1.5 depends on the extracellular pH. European Journal of Pharmacology, v. 960, p. 12-pg., 2023-10-24. (21/05584-7, 19/18918-0, 21/15122-0, 20/14635-1)