The insecticide β-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype. Issue 5 (18th March 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Clinical science. Volume 136:Issue 5(2022)
• Page Start: 329
• Page End: 343
• Publication Date: 2022-03-18
• Subjects: β-Cyfluthrin -- arrhythmias -- INa-L -- insecticide -- pyrethroid -- ranolazine; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20211151
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: β-Cyfluthrin, a class II Pyrethroid, is an insecticide used worldwide in agriculture, horticulture (field and protected crops), viticulture, and domestic applications. β-Cyfluthrin may impair the function of biological systems; however, little information is available about its potential cardiotoxic effect. Here, we explored the acute toxicity of β-Cyfluthrin in isolated heart preparations and its cellular basis, using isolated cardiomyocytes. Moreover, β-Cyfluthrin effects on the sodium current, especially late sodium current (INa-L ), were investigated using human embryonic kidney cells (HEK-293) cells transiently expressing human NaV1.5 channels. We report that β-Cyfluthrin raised INa-L in a dose-dependent manner. β-Cyfluthrin prolonged the repolarization of the action potential (AP) and triggered oscillations on its duration. Cardiomyocytes contraction and calcium dynamics were disrupted by the pesticide with a marked incidence of non-electronic-stimulated contractions. The antiarrhythmic drug Ranolazine was able to reverse most of the phenotypes observed in isolated cells. Lastly, ventricular premature beats (VPBs) and long QT intervals were found during β-Cyfluthrin exposure, and Ranolazine was able to attenuate them. Overall, we demonstrated that β-Cyfluthrin can cause significant cardiac alterations and Ranolazine ameliorated the phenotype. Understanding the insecticides' impacts upon electromechanical properties of the heart is important for the development of therapeutic approaches to treat cases of pesticides intoxication.