IN VIVO ADMINISTRATION OF THE PYRETHROID BIFENTHRIN CAUSES ELECTRICAL REMODELING IN THE RAT HEARTS

The modernization of agriculture through mechanization and the intensive use of chemical such as fertilizers and pesticides has been crucial for increased productivity and global food security. However, exposure to pesticides like bifenthrin (BF) has raised concerns due to associated health risks in non-target organisms. This study aimed to assess the subacute effects of BF on cardiac function using electrocardiographic and histomorphometric parameters in Wistar rats. All procedures were approved by the Animal Ethics Committee of the Federal University of São Paulo (nº 4209080223). Male Wistar rats (~100g) were randomly assigned to four groups: (I) Control (CTRL), receiving corn oil (1mL/kg/day) by gavage for 28 days; and (II) BF-treated, receiving 0.01mg, (III) BF-treated 0.1mg, or (IV) BF-treated 1mg/kg/day of BF orally for the same period. Electrocardiograms (ECG) were performed on days 0, 14, and 28. To assess arrhythmia susceptibility, animals received caffeine (120mg/kg, i.p.) and dobutamine (1mg/kg, i.p.) at the end of the treatment. There were no significant differences in body weight or organ weights (heart, lungs, liver, spleen, kidneys) across groups. Histological analysis of the left ventricle revealed no signs of cardiomyocyte hypertrophy, as indicated by unchanged cross-sectional area. However, ECG analysis showed a significant increase in P wave duration in the BF 1 mg/kg group on days 14 and 28, as well as prolonged QT interval on day 28. No differences were observed in PR interval, QRS complex, or RR interval. Under pharmacological stress with caffeine and dobutamine, arrhythmic events, such as premature ventricular contractions and atrioventricular blocks, were observed in all BF-treated groups, with incidence rates of 20%, 50%, and 62.5% for 0.01, 0.1, and 1 mg/kg, respectively, being statistically significant in the dose 0,1 e 1mg/kg, while the arrhythmia score showed a non-significant trend toward elevation. TTC staining revealed a significant increase in myocardial infarct area in the BF 1 mg/kg group. Serum biomarkers (CK-MB and LDH) remained unchanged. These findings suggest that subacute exposure to BF may promote electrophysiological alterations and increase susceptibility to arrhythmias and myocardial injury under cardiac stress conditions in rats.

This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grants nº 2023/04603-3, 2021/05584-7, 2022/14133-1, 2021/15122-0, 2022/07256-0, 2024/06444-2).