Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats. (January 2020)

• Record Type: Journal Article
• Authors: Zhan, Chengchuang; Liu, Guangzhong; Li, Jianqiang; Li, Guangnan; Li, Tiankai; Zhao, Hongyan; Li, Luyifei; Yang, Wen; Bai, Nan; Zheng, Min; Yang, Junfen; Li, Weimin
• Is Part Of: Toxicology letters. Volume 318(2020)
• Page Start: 57
• Page End: 64
• Publication Date: 2020-01
• Subjects: 3-BrPA 3-bromopyruvate -- SCD sudden cardiac death -- ECG electrocardiogram -- HK hexokinase -- PVDF polyvinylidene difluoride -- QTc corrected QT interval -- TBST Tris-buffered saline with Tween -- VERP ventricular effective refractory period -- VT/VF ventricular tachycardia/ventricular fibrillation; 3-BrPA -- Rotenone -- Arrhythmia -- Structural remodeling -- Electrical remodeling; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2019.09.024
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Rotenone contributed to SCD by increasing the risk of fatal arrhythmias. 3-BrPA did not induce the occurrence of fatal arrhythmias in rats. 3-BrPA had no influence electrical and structural cardiac remodeling in rats. Rotenone combined with 3-BrPA had a strong effect on cardiac remodeling. Abstract: 3-Bromopyruvate (3-BrPA) is a promising agent that has been widely studied in the treatment of cancer and pulmonary hypertension. Rotenone is a pesticide commonly used on farms and was shown to have anti-cancer activity and delay fibrosis progression in chronic kidney disease in a recent study. However, there are few studies showing the toxicity of rotenone and 3-BrPA in the myocardium. To support further medical exploration, it is necessary to clarify the side effects of these compounds on the heart. This study was designed to examine the cardiotoxicity of 3-BrPA and rotenone by investigating electrical and structural cardiac remodeling in rats. Forty male rats were divided into 4 groups (n = 10 in each group) and injected intraperitoneally with 3-BrPA, rotenone or a combination of 3-BrPA and rotenone. The ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/ventricular fibrillation (VT/VF) inducibility were measured. The expression of Cx43, Kir2.1, Kir6.2, DHPRα1, KCNH2, caspase3, caspase9, Bax, Bcl2, and P53 was detected. Masson's trichrome, TUNEL, HE, and PAS staining and transmission electron microscopy were used to detect pathological and ultrastructural changes. Our results showed that rotenone alone and rotenone combined with 3-BrPA significantly increased the risk of ventricular arrhythmias. Rotenone combined with 3-BrPA caused myocardial apoptosis, and rotenone alone and rotenone combined with 3-BrPA caused electrical and structural cardiac remodeling in rats.