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Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil

Grant number: 21/05584-7
Support Opportunities:Research Grants - Young Investigators Grants - Phase 2
Duration: September 01, 2022 - August 31, 2027
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Principal Investigator:Danilo Roman Campos
Grantee:Danilo Roman Campos
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated researchers: Adriano de Jesus da Silva ; DANIELLE OLIVEIRA COSTA SANTOS ; Dr Udo Kraushaar ; Fernando Augusto de Oliveira Ribeiro ; João Bosco Pesquero ; Marcela Sorelli Carneiro Ramos ; Zhiguang Yuchi
Associated research grant:14/09861-1 - The role of late sodium current in the inherited and acquired cardiac arrhythmias: from the biophysics properties to new therapeutic targets, AP.JP
Associated scholarship(s):22/14133-1 - 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, BP.PD
23/11912-2 - Pesticide as an enhancement factor for Doxorubicin-induced cardiotoxicity, BP.PD
23/04603-3 - Evaluation of in vivo cardiotoxicity of oral exposure to the triazol tebuconazole and the pyrethroid Bifenthrin, BP.DR
+ associated scholarships 23/04028-9 - Morphofunctional studies of cardiotoxicity induced by the pesticide chlorpyrifos, BP.IC
21/15122-0 - CARDIOTOXICITY INDUCED BY THE PESTICIDE TEBUCONAZOLE IN MICE: FROM CONCEPTION TO ADULT LIFE, BP.DR
22/07256-0 - Role of SCN5A polymorphisms on pharmacological properties of pesticides against Nav1.5, BP.PD - associated scholarships

Abstract

Brazil is the third country in the world in total tons of pesticides use per year. Pesticides are toxic substances or a mixture of substances that are naturally or chemically synthesized. They are widely used in agriculture to control plagues; however, since they are toxic to life, they are inevitably toxic to humans. Heavy use of pesticides has contaminated ecosystems. In Brazil, at least 27 pesticides are found in potable water, with a range of concentrations. Ministry of Health set concentration threshold levels for each pesticide, in theory not toxic, allowed to be found in potable water. However, in the literature, there is no systematic investigation of heart and nervous system toxicity of human tissue by these compounds at concentrations set by Ministry of Health. Also, there is no information if a mixture of these pesticides potentiates toxicity. Thus, to address these questions, we had the following aims: 1) evaluate in vitro single or mixture of pesticides in acute and chronic toxicity for cardiomyocytes and neurons derived from human-induced pluripotent stem cells, using the concentration approved by the Ministry of Health; 2) using mice determine in vivo if long-term low dose of single or a mixture of pesticides impact the functioning of the heart and central nervous system; 3) investigate in vivo how long-term low-dose pesticides impact the functioning of the heart and central nervous system in offspring of pregnant mice exposed to pesticides during pregnancy; 4) if SCN5A polymorphisms enhance the potency and toxicity of pesticides in vitro. At the end we will be able to determine the safety of potable water of Brazil in terms of pesticide contamination or if changes are needed in the guidelines of Ministry of Health. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
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Scientific publications (9)
(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)
SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, V. JULLIANE; CRUZ-NASCIMENTO, TAYNARA; NERI, ELIDA ADALGISA; SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; KRIEGER, JOSE E.; ROMAN-CAMPOS, DANILO. The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine heart and human cardiomyocytes derived from induced pluripotent stem cells. Toxicology Letters, v. 359, p. 10-pg., . (18/22830-9, 19/18918-0, 21/05584-7, 19/21304-4, 20/14635-1, 18/20777-3)
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., . (21/15122-0, 21/05584-7, 19/18918-0)
DA SILVA, MARIA VITORIA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE, V; SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; SARMENTO, JAQUELINE OLIVEIRA; BESERRA, SAMUEL SANTOS; ROMAN-CAMPOS, DANILO. The insecticide beta-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype. Clinical Science, v. 136, n. 5, p. 15-pg., . (21/05584-7, 19/18918-0, 18/20777-3, 18/22830-9, 20/09403-4, 19/21304-4)
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 NaV1.5 channels expressed in HEK293 cells. Food and Chemical Toxicology, v. 180, p. 12-pg., . (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., . (19/21304-4, 19/18918-0, 21/15122-0, 20/14635-1, 21/05584-7)
TEIXEIRA-FONSECA, JORGE LUCAS; DE LIMA CONCEICAO, MICHAEL RAMON; LEAL-SILVA, POLYANA; ROMAN-CAMPOS, DANILO. Ranolazine exerts atrial antiarrhythmic effects in a rat model of monocrotaline-induced pulmonary hypertension. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. 132, n. 5, p. 10-pg., . (19/21304-4, 21/05584-7)
JORGE LUCAS TEIXEIRA-FONSECA; JULLIANE VASCONCELOS JOVIANO-SANTOS; FABIANA DA SILVA ALCÂNTARA; POLYANA LEAL DA SILVA; MICHAEL RAMON LIMA CONCEIÇÃO; DANILO ROMAN-CAMPOS. Estudo Morfofuncional do Átrio Esquerdo Isolado de um Modelo Experimental de Hipertensão Pulmonar em Ratos. Arquivos Brasileiros de Cardiologia, v. 120, n. 10, . (21/05584-7, 19/21304-4)
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., . (21/15122-0, 20/14635-1, 21/05584-7, 19/18918-0)
SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; COSTA, ALEXANDRE DANTAS; CRUZ, JADER SANTOS; RHANA, PAULA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE VASCONCELOS; DURCO, AIMEE OBOLARI; LINS VASCONCELOS, CARLA MARIA; ROMAN-CAMPOS, DANILO. Experimental hypothyroidism induces cardiac arrhythmias and ranolazine reverts and prevents the phenotype. Life Sciences, v. 308, p. 13-pg., . (20/14635-1, 21/05584-7, 19/21304-4, 19/18918-0)

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