Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats
Rotenone and 3-bromopyruvate toxicity impacts electrical and structural cardiac remodeling in rats
复制标题
鱼藤酮和 3-溴丙酮酸毒性影响大鼠的电和结构性心脏重塑。
DOI：
10.1016/j.toxlet.2019.09.024
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发表时间：
2020-01-01
影响因子：
3.5
通讯作者：
Li, Weimin
中科院分区：
文献类型：
--
作者：
Zhan, Chengchuang;Liu, Guangzhong;Li, Weimin
3-溴丙酮酸（3-BrPA）是一种很有前途的药物，已被广泛研究用于治疗癌症和肺动脉高压。鱼藤酮是一种常用于农场的杀虫剂，在最近的一项研究中显示具有抗癌活性，并延缓慢性肾脏疾病的纤维化进展。然而，很少有研究表明鱼藤酮和3-BrPA在心肌中的毒性。为了支持进一步的医学探索，有必要澄清这些化合物对心脏的副作用。本研究旨在通过研究大鼠心脏电重构和结构重构来研究3-BrPA和鱼藤酮的心脏毒性。将40只雄性大鼠分为4组（每组n=10），分别腹腔注射3-BrPA、鱼藤酮或3-BrPA和鱼藤酮的组合。测定心室有效不应期（VERP）、校正QT间期（QTc）、室性心动过速/室颤（VT/VF）诱发率。检测Cx43、Kir2.1、Kir6.2、DHPR α（1）、KCNH 2、caspase 3、caspase 9、Bax、Bcl 2、P53的表达。采用Masson三色染色、TUNEL、HE、PAS染色及透射电镜观察病理及超微结构变化。我们的研究结果表明，单独使用鱼藤酮和鱼藤酮与3-BrPA联合使用显著增加了室性心律失常的风险。鱼藤酮与3-BrPA合用可引起大鼠心肌细胞凋亡，鱼藤酮单独及鱼藤酮与3-BrPA合用可引起大鼠心肌电重构和结构重构。
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, DHPR alpha(1), 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.