The Cardiotoxic Effect of Roundup® is not Induced by Glyphosate: A Non-specific Blockade of Human CaV1.2 Channels.

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 (100µM). 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 CaV1.2 with an IC50 value of 3.76µM. 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 100µM (- 27.2 ± 1.7%, p < 0.01). In conclusion, Roundup® could induce severe cardiac toxicity by a blockade of CaV1.2 channel, leading to a worsening of heart contractility and genesis of arrhythmias. This toxicity could not be attributed to glyphosate.