Molecular mechanisms of increased susceptibility to cardiac arrhythmias due to chronic in vivo exposure to low doses of triazole pesticides: implications for worsening heart disease caused by Pulmonary Hypertension

• Grant number: 22/14133-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Danilo Roman Campos
• Grantee: Jorge Lucas Teixeira da Fonseca
• 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

In recent decades, the demand for pesticides has grown significantly. However, inappropriate use poses a serious risk to humans and wildlife. Diphenoconazole, prothioconazole and tebuconazole are all antifungal pesticides with systemic action in the triazole class, and are leaders in their class in terms of sales and use. Due to their physicochemical characteristics, they are found in soil, water and commercialized foods, thus leading a significant portion of the population to long-term exposure to fungicides. However, the molecular mechanisms of the possible cardiotoxicity induced by the pesticides difenoconazole, prothioconazole and tebuconazole are not known. Furthermore, it is not publicly or scientifically known whether pre-existing heart disease can potentiate the cardiotoxic effect of these compounds. Furthermore, the minimum dose administered in vivo of difenoconazole, prothioconazole and tebuconazole that does not cause an adverse effect on heart and lung tissue (NOAEL, no observable adverse effect level) is not known. Therefore, in this project we will focus on clarifying the following topics involving the three compounds: 1) Determining the NOAEL for the heart; 2) Understanding the molecular mechanisms of fungicide-induced cardiotoxicity; 3) Evaluating whether pre-existing diseases potentiate the cardiotoxic effect of pesticides, using a model of right-sided heart disease induced by pulmonary hypertension. (AU)

Scientific publications

(4)

(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)

CONCEICAO, MICHAEL RAMON DE LIMA; TEIXEIRA-FONSECA, JORGE LUCAS; ORTS, DIEGO JOSE BELATO; NASCIMENTO, DANIELLA SANTOS; DANTAS, CACIA OLIVEIRA; DE VASCONCELOS, CARLA MARIA LINS; SOUZA, DIEGO SANTOS; ROMAN-CAMPOS, DANILO. Exploring the interplay between extracellular pH and Dronedarone's pharmacological effects on cardiac function. European Journal of Pharmacology, v. 983, p. 11-pg., 2024-09-12. (24/06444-2, 22/07256-0, 22/14133-1, 21/05584-7, 20/14635-1)

DURCO, AIMEE OBOLARI; SOUZA, DIEGO SANTOS; CONCEICAO, MICHAEL RAMON DE LIMA; BESERRA, SAMUEL DOS SANTOS; DA FONSECA, JORGE LUCAS TEIXEIRA; LOCH, LEONARDO; SILVA, MICHEL AUGUSTO; DE OLIVEIRA, ALDEIDIA PEREIRA; ARAUJO, ADRIANO ANTUNES DE SOUZA; DE VASCONCELOS, CARLA MARIA LINS; et al. D-limonene complexed with hydroxypropyl-(3-cyclodextrin prevents impaired cardiac excitation-contraction coupling by reducing oxidative stress and cardiac apoptosis in an animal model of cardiotoxicity induced by doxorubicin. Chemico-Biological Interactions, v. 418, p. 10-pg., 2025-09-05. (21/05584-7, 23/11912-2, 22/14133-1, 24/06444-2, 20/14635-1, 09/53840-0)

JORGE LUCAS TEIXEIRA-FONSECA; DIEGO JOSE BELATO Y ORTS; POLYANA LEAL DA SILVA; MICHAEL RAMON DE LIMA CONCEIÇÃO; HERNAN HERMES; CARLOS R. PRUDENCIO; DANILO ROMAN-CAMPOS. Atividade Anti-Inflamatória In Vivo do D-Limoneno em um Modelo de Hipertensão Pulmonar Induzida por Monocrotalina em Ratos: Implicações à Função Cardíaca. Arquivos Brasileiros de Cardiologia, v. 121, n. 12, 2024-12-13. (21/05584-7, 22/14133-1, 20/14635-1, 22/07256-0)

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)