title: 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.
authors.affiliation: Institute of Biology, Risk Pole, MRSH-CNRS, EA 2608 Estrogen, Reproduction and Cancer, University of Caen, Esplanade de la Paix, 14032, Caen Cedex, France.|Institute of Biology, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, University of Caen, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Steeve
authors.initials: S
authors.lastname: Gress
authors.affiliation: Institute of Biology, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, University of Caen, Esplanade de la Paix, 14032, Caen Cedex, France.|Department of Anesthesiology and Critical Care Medicine, University Hospital of Caen, 14033, Caen Cedex, France.|Faculty of Medicine, University of Caen, Caen, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: Laboratory of Biotechnologies Applied to Cardiovascular Medicine, Department of Cardiovascular Sciences, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico, 155, 00161, Rome, Italy. paoloemilio.puddu@uniroma1.it.
authors.forename: Paolo-Emilio
authors.initials: PE
authors.lastname: Puddu
authors.affiliation: Institute of Biology, Risk Pole, MRSH-CNRS, EA 2608 Estrogen, Reproduction and Cancer, University of Caen, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Gilles-Eric
authors.initials: GE
authors.lastname: Séralini
authors.affiliation: Institute of Biology, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d'ischémie-reperfusion myocardique, University of Caen, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: René
authors.initials: R
authors.lastname: Rouet
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000633:toxicity; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006540:Herbicides / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D000097797:Glyphosate
chemical_list: D002118:Calcium; D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D005998:Glycine; D006540:Herbicides; D000254:Sodium-Potassium-Exchanging ATPase; D000097797:Glyphosate
keywords: Action potential duration; Calcium; Conduction blocks; Glyphosate; Pro-arrhythmia; Roundup