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草甘膦除草剂的心脏毒性并非由草甘膦引起:对人Ca1.2通道的非特异性阻断

The Cardiotoxic Effect of Roundup® is not Induced by Glyphosate: A Non-specific Blockade of Human Ca1.2 Channels.

作者信息

Printemps Richard, Guilbot Stéphanie, Didier Hélène, Nalin Renaud, Le Grand Bruno

机构信息

PhysioStim, 10 rue Henri Regnault, 81100, Castres, France.

出版信息

Cardiovasc Toxicol. 2022 Jul;22(7):676-688. doi: 10.1007/s12012-022-09749-3. Epub 2022 May 20.

Abstract

In Roundup®, the active principle glyphosate is formulated with adjuvants that help it to penetrate the plants' cell membranes. Several reports and reviews report cardiovascular effects of Roundup®, pointing the presence of arrhythmias as a potential consequence of Roundup® toxicity and death cause. However, it still remains debatable whether these cardiac events are related to glyphosate per se or to the Roundup® adjuvants. The present study aims to compare the pro-arrhythmogenic properties of Roundup® and glyphosate in an animal model and in human cardiomyocytes. In isolated guinea pig heart, the cardiotoxicity of Roundup® (significant effect on heart rate and depressive effect on ventricular contractility) was demonstrated with the highest concentrations (100 µM). In human cardiomyocytes, the cardiotoxicity is confirmed by a marked effect on contractility and a strong effect on cell viability. Finally, this Roundup® depressive effect on heart contractility is due to a concentration-dependent blocking effect on cardiac calcium channel Ca1.2 with an IC value of 3.76 µM. Surprisingly, no significant effect on each parameter has been shown with glyphosate. Glyphosate was devoid of major effect on cardiac calcium channel with a maximal effect at 100 µM (- 27.2 ± 1.7%, p < 0.01). In conclusion, Roundup® could induce severe cardiac toxicity by a blockade of Ca1.2 channel, leading to a worsening of heart contractility and genesis of arrhythmias. This toxicity could not be attributed to glyphosate.

摘要

在农达®中,活性成分草甘膦与有助于其穿透植物细胞膜的助剂混合配制。一些报告和综述指出了农达®对心血管的影响,指出心律失常是农达®毒性和致死原因的潜在后果。然而,这些心脏事件是与草甘膦本身还是与农达®助剂有关仍存在争议。本研究旨在比较农达®和草甘膦在动物模型和人类心肌细胞中的促心律失常特性。在离体豚鼠心脏中,最高浓度(100μM)的农达®表现出心脏毒性(对心率有显著影响,对心室收缩力有抑制作用)。在人类心肌细胞中,对收缩力的显著影响和对细胞活力的强烈影响证实了其心脏毒性。最后,农达®对心脏收缩力的抑制作用是由于对心脏钙通道Ca1.2的浓度依赖性阻断作用,IC值为3.76μM。令人惊讶的是,草甘膦对每个参数均未显示出显著影响。草甘膦对心脏钙通道无主要影响,在100μM时最大效应为(-27.2±1.7%,p<0.01)。总之,农达®可能通过阻断Ca1.2通道诱导严重的心脏毒性,导致心脏收缩力恶化和心律失常的发生。这种毒性不能归因于草甘膦。

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