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Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats
Chengchuang Zhan1, Guangzhong Liu1, Jianqiang Li1
1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
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.
Insights
Rotenone, a pesticide, and 3-Bromopyruvate (3-BrPA) can cause heart problems. This study found that rotenone, especially when combined with 3-BrPA, increases the risk of dangerous heart rhythms and cardiac remodeling.
Area of Science:
- Cardiovascular Toxicology
- Pharmacology
- Biochemistry
Background:
- 3-Bromopyruvate (3-BrPA) is investigated for cancer and pulmonary hypertension treatment.
- Rotenone, a pesticide, exhibits anti-cancer properties and delays fibrosis in kidney disease.
- Limited data exists on the cardiotoxicity of rotenone and 3-BrPA.
Purpose of the Study:
- To investigate the cardiotoxicity of 3-Bromopyruvate (3-BrPA) and rotenone.
- To examine electrical and structural cardiac remodeling induced by these compounds in rats.
Main Methods:
- Male rats were administered 3-BrPA, rotenone, or a combination.
- Measurements included ventricular effective refractory period (VERP), corrected QT interval (QTc), and ventricular tachycardia/fibrillation (VT/VF) inducibility.
- Cardiac gene expression, pathological, and ultrastructural changes were analyzed.
Main Results:
- Rotenone and the combination of rotenone with 3-BrPA significantly elevated the risk of ventricular arrhythmias.
- The combination induced myocardial apoptosis.
- Both rotenone alone and in combination induced electrical and structural cardiac remodeling.
Conclusions:
- Rotenone poses a significant risk for cardiotoxicity, particularly when combined with 3-BrPA.
- These findings highlight the potential cardiac side effects of rotenone and 3-BrPA, necessitating caution in their medical exploration.
