The fungicide tebuconazole modulates the sodium current of human Na_V1.5 channels expressed in HEK293 cells

Autor(es)

Marques, Leisiane Pereira ; Santos-Miranda, Artur ; Joviano-Santos, Julliane Vasconcelos ; Teixeira-Fonseca, Jorge Lucas ; Alcantara, Fabiana da Silva ; Sarmento, Jaqueline Oliveira ; Roman-Campos, Danilo

• Tipo de documento: Artigo Científico
• Fonte: Food and Chemical Toxicology; v. 180, p. 12-pg., 2023-08-30.

Resumo

The fungicide Tebuconazole is a widely used pesticide in agriculture and may cause cardiotoxicity. In our present investigation the effect of Tebuconazole on the sodium current (I-Na) of human cardiac sodium channels (Na(V)1.5) was studied using a heterologous expression system and whole-cell patch-clamp techniques. Tebuconazole reduced the amplitude of the peak I-Na in a concentration- and voltage-dependent manner. At the holding potential of -120 mV the IC50 was estimated at 204.1 & PLUSMN; 34.3 & mu;M, while at -80 mV the IC50 was 0.3 & PLUSMN; 0.1 & mu;M. The effect of the fungicide is more pronounced at more depolarized potentials, indicating a state-dependent interaction. Tebuconazole caused a negative shift in the half-maximal inactivation voltage and delayed recovery from fast inactivation of I-Na. Also, it enhanced closed-state inactivation, exhibited use-dependent block in a voltage-dependent manner. Furthermore, Tebuconazole reduced the increase in late sodium current induced by the pyrethroid insecticide & beta;-Cyfluthrin. These results suggest that Tebuconazole can interact with Na(V)1.5 channels and modulate I-Na. The observed effects may lead to decreased cardiac excitability through reduced I-Na availability, which could be a new mechanism of cardiotoxicity to be attributed to the fungicide. (AU)

• Processo FAPESP: 21/15122-0 - Cardiotoxicidade induzida pelo pesticida tebuconazol em camundongos: da concepção a vida adulta
• Beneficiário: Leisiane Pereira Marques
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 20/14635-1 - Modelagem de doenças monogênicas para estudos fisiopatológicos e testes farmacológicos utilizando células especializadas derivadas de iPSCs
• Beneficiário: João Bosco Pesquero
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 21/05584-7 - Avaliação da toxicidade aguda e crônica ao coração e ao cérebro expostos a pesticidas encontrados na água potável do Brasil
• Beneficiário: Danilo Roman Campos
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2