Acute exposure to low-dose bisphenol A delays cardiac repolarization in female canine heart – Implication for proarrhythmic toxicity in large animals. (February 2023)

• Record Type: Journal Article
• Authors: Ma, Jianyong; Niklewski, Paul J.; Wang, Hong-Sheng
• Is Part Of: Food and chemical toxicology. Volume 172(2023)
• Publication Date: 2023-02
• Subjects: Bisphenol A -- Canine heart -- Low dose -- hERG channel -- QT prolongation -- Arrhythmia marker; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.113589
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Bisphenol A (BPA) is a common environmental chemical with a range of potential adverse health effects. The impact of environmentally-relevant low dose of BPA on the electrical properties of the hearts of large animals (e.g., dog, human) is poorly defined. Perturbation of cardiac electrical properties is a key arrhythmogenic mechanism. In particular, delay of ventricular repolarization and prolongation of the QT interval of the electrocardiogram is a marker for the risk of malignant arrhythmias. We examined the acute effect of 10 −9 M BPA on the electrical properties of female canine ventricular myocytes and tissues. BPA rapidly delayed action potential repolarization and prolonged action potential duration (APD). The dose response curve of BPA on APD was nonmonotonic. BPA rapidly inhibited the IKr K + current and ICaL Ca 2+ current. Computational modeling indicated that the effect of BPA on APD can be accounted for by its suppression of IKr . At the tissue level, BPA acutely prolonged the QT interval in 4 left ventricular wedges. ERβ signaling contributed to the acute effects of BPA on ventricular repolarization. Our results demonstrate that BPA has QT prolongation liability in female canine hearts. These findings have implication for the potential proarrhythmic cardiac toxicity of BPA in large animals.