Cardiotoxic Electrophysiological Effects of the Herbicide Roundup® in Rat and Rabbit Ventricular Myocardium In Vitro

Abstract

Roundup (R), a glyphosate (G)-based herbicide (GBH), containing unknown adjuvants is widely dispersed around the world. Used principally by farmers, intoxications have increasingly been reported. We have studied R effects (containing 36 % of G) on right ventricular tissues (male Sprague–Dawley rats, up to 20,000 ppm and female New Zealand rabbits, at 25 and 50 ppm), to investigate R cardiac electrophysiological actions in vitro. We tested the reduced Ca++ intracellular uptake mechanism as one potential cause of the electrical abnormalities after GBH superfusion, using the Na+/K+-ATPase inhibitor ouabain or the 1,4-dihydropyridine L-type calcium channel agonist BAY K 8644 which increases I Ca. R concentrations were selected based on human blood ranges found after acute intoxication. The study showed dose-dependent V max, APD50 and APD90 variations during 45 min of R superfusion. At the highest concentrations tested, there was a high incidence of conduction blocks, and 30-min washout with normal Tyrode solution did not restore excitability. We also observed an increased incidence of arrhythmias at different doses of R. Ouabain and BAY K 8644 prevented V max decrease, APD90 increase and the cardiac inexcitability induced by R 50 ppm. Glyphosate alone (18 and 180 ppm) had no significant electrophysiological effects. Thus, the action potential prolonging effect of R pointing to I Ca interference might explain both conduction blocks and proarrhythmia in vitro. These mechanisms may well be causative of QT prolongation, atrioventricular conduction blocks and arrhythmias in man after GBH acute intoxications as reported in retrospective hospital records.

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Acknowledgments

We wish to thank Josefa de Flores Martos Borrego to her technical help for these experiments. We thank also Nature Vivante and CRIIGEN for fellowship grants to Steeve Gress during the development of his Doctoral Thesis to obtain PhD degree in Molecular and Cellular Biology of the University of Caen Basse-Normandie, France.

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The authors declare that there are no conflicts of interest.

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Correspondence to Paolo-Emilio Puddu.

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Gress, S., Lemoine, S., Puddu, P. et al. Cardiotoxic Electrophysiological Effects of the Herbicide Roundup® in Rat and Rabbit Ventricular Myocardium In Vitro. Cardiovasc Toxicol 15, 324–335 (2015). https://doi.org/10.1007/s12012-014-9299-2

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Keywords

  • Roundup
  • Glyphosate
  • Action potential duration
  • Conduction blocks
  • Pro-arrhythmia
  • Calcium