Daily exposure to chlordecone, an organochlorine pesticide, increases cardiac fibrosis and atrial fibrillation vulnerability.

Journal of hazardous materials Pub Date : 2024-10-05 Epub Date: 2024-08-14 DOI:10.1016/j.jhazmat.2024.135533
Alexia Fundere, Andrew Rose, Feng Xiong, Kalai Mangai Muthukumarasamy, Yasemin Altuntas, Harika Dasari, Louis Villeneuve, Martin G Sirois, Jean-François Tanguay, Jean-Claude Tardif, Roddy Hiram
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Abstract

Context: Chlordecone (CLD) is a carcinogenic organochlorine pesticide. CLD was shown to disturb the activity of cardiac Na+-K+-ATPase and Ca2+-Mg2+-ATPase. Conditions affecting these transmembrane pumps are often associated with cardiac arrhythmias (CA). However, little is known about the role of CLD on atrial fibrillation (AF) incidence, the most common type of CA.

Hypotheses: 1) Daily ingestion of CLD induces arrhythmogenic cardiac remodeling. 2) A phase of CLD withdrawal can reduce CLD-induced AF susceptibility.

Methods: Adult male Wistar rats (250 g-275 g) ingested daily-doses of CLD (0 μg/L, 0.1 μg/L, or 1 μg/L) diluted in their quotidian water for 4 weeks. From day (D)29 to D56, all rats received CLD-free water. Vulnerability to AF and cardiac function were evaluated at D28 and D56 by electrophysiological study, echocardiography, and optical-mapping. Levels of genes and proteins related to inflammation, fibrosis, and senescence were quantified by qPCR and immunoassays.

Results: Twenty-eight days of CLD exposure were associated with significantly increased AF vulnerability compared to CLD-free rats. Contamination with 1 μg/L CLD significantly reduced atrial conduction velocity (ERP, APD). CLD-weaning normalized food consumption and weight intake. However, after the CLD-withdrawal period of 28 days, AF inducibility, atrial inflammation (IL6, IL1β), and atrial fibrosis (Masson's trichrome staining) remained significantly higher in rats exposed to 1 μg/L CLD compared to 0 μg/L.

Conclusions: Prolonged CLD ingestion provokes atrial conduction slowing and increased risk of AF. Although CLD-weaning, some persistent damages occurred in the atrium like atrial fibrosis and atrial senescence signals, which are accompanied by atrial inflammation and arrhythmogenicity.

每天接触十氯酮(一种有机氯杀虫剂)会增加心脏纤维化和心房颤动的可能性。
背景:十氯酮(CLD)是一种致癌的有机氯杀虫剂:十氯酮(CLD)是一种致癌的有机氯杀虫剂。研究表明,CLD 会干扰心脏 Na+-K+-ATPase 和 Ca2+-Mg2+-ATPase 的活性。影响这些跨膜泵的情况通常与心律失常(CA)有关。然而,CLD 对心房颤动(AF)发病率(最常见的心律失常类型)的作用却知之甚少:1)每天摄入 CLD 会诱发心律失常性心脏重塑。2)停用 CLD 的阶段可降低 CLD 诱导的房颤易感性:方法:成年雄性 Wistar 大鼠(250 克-275 克)每天摄入稀释在饮水中的 CLD(0 μg/L、0.1 μg/L 或 1 μg/L),连续摄入 4 周。从第 29 天到第 56 天,所有大鼠都饮用不含 CLD 的水。在第 28 天和第 56 天,通过电生理学研究、超声心动图和光学绘图评估房颤的易感性和心脏功能。通过 qPCR 和免疫测定量化了与炎症、纤维化和衰老相关的基因和蛋白质水平:结果:与无 CLD 的大鼠相比,暴露于 CLD 28 天的大鼠房颤易损性显著增加。1 μg/L CLD 污染显著降低了心房传导速度(ERP、APD)。CLD断奶使大鼠的食量和体重恢复正常。然而,在28天的CLD戒断期后,与0 μg/L的大鼠相比,摄入1 μg/L CLD的大鼠房颤诱发率、心房炎症(IL6、IL1β)和心房纤维化(Masson三色染色)仍然显著较高:结论:长期摄入CLD会导致心房传导减慢,增加房颤风险。结论:长期摄入 CLD 会导致心房传导减慢,增加房颤风险。虽然 CLD 已减弱,但心房中仍存在一些持续性损伤,如心房纤维化和心房衰老信号,并伴有心房炎症和致心律失常性。
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