Role of SCN5A polymorphisms on pharmacological properties of pesticides against Nav1.5

• Grant number: 22/07256-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2022
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Danilo Roman Campos
• Grantee: Diego Jose Orts y Belato
• 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

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. In Brazil, at least 27 pesticides are found in potable water, with a range of concentrations. Ministry of Health set nontoxic concentration threshold levels for each pesticide allowed to be found in potable water. Several ion channels contribute to the control of cardiomyocyte excitability. The isoform 1.5 of the voltage-gated sodium channel (Nav1.5) is responsible for the rising phase of action potential in cardiomyocytes. Several genetic single point mutation polymorphisms are found and four of them with non-pathological implications occur in higher frequency in the SCN5A gene, which is gives the alpha-pore subunit of Nav1.5: S524Y (found in 3.3% of African Americans), S1103Y (6.5% in African Americans), R1193Q (8% in Asians) and V1951L (6,7% in Hispanics). Although these polymorphisms have not been associated with a specific disease, they contribute to the binding of different drugs in the Nav1.5 channel. Moreover, SCN5A polymorphisms have been proposed to enhance the affinity of drugs, including pesticides, to the Nav1.5 channel contributing to the toxicology of pesticides in humans. Thus, the main questions that motivated our research group are: (1) Does most common SCN5A polymorphisms enhance potency of relevant pesticides found in Brazilian potable water upon human Nav1.5?; (2) Does part of the Brazilian population is more susceptible to pesticides toxicity? We expect our results contribute to the investigation field of ion channel polymorphisms and its correlation with pesticide toxicity, which has been completely neglected in the current literature. At the end we expect to be able to determine the safety of potable water of Brazil in terms of pesticide contamination or if changes in the guidelines of Ministry of Health will be needed. (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)

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. (20/14635-1, 22/14133-1, 21/05584-7, 22/07256-0)

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)

TEIXEIRA-FONSECA, JORGE LUCAS; BELATO Y ORTS, DIEGO JOSE; DA SILVA, POLYANA LEAL; CONCEICAO, MICHAEL RAMON DE LIMA; HERMES, HERNAN; PRUDENCIO, CARLOS R.; ROMAN-CAMPOS, DANILO. In Vivo Anti-Inflammatory Activity of D-Limonene in a Rat Model of Monocrotaline-Induced Pulmonary Hypertension: Implications to the. Arquivos Brasileiros de Cardiologia, v. 121, n. 12, p. 11-pg., 2024-01-01. (21/05584-7, 22/07256-0, 20/14635-1)

DA COSTA, HERNAN H. M.; BIELAVSKY, MONICA; ORTS, DIEGO J. B.; ARAUJO, SERGIO; ADRIANI, PATRICIA P.; NOGUEIRA, JULIANA S.; ASTRAY, RENATO M.; PANDEY, RAMENDRA P.; LANCELLOTTI, MARCELO; CUNHA-JUNIOR, JAIR P.; et al. Production of Recombinant Zika Virus Envelope Protein by Airlift Bioreactor as a New Subunit Vaccine Platform. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 18, p. 25-pg., 2023-09-01. (22/07256-0, 21/11936-3, 17/50333-7)