Pesticide exposure an unforseen trigger for atrial fibrillation

Abstract

Abstract Background/Introduction Over the last few decades, the use of pesticides for improving crop yield has continued to soar. Recent evidence shows the residuals of pesticides in many fruits and vegetables in the local supermarket. Although acute exposure to pesticides has been related to various severe illness, including cardiovascular dysfunction, chronic pesticide exposure has been poorly studied. Herein we study the cardiotoxic effect of commonly used pesticides to the most common cardiac arrhythmia, atrial fibrillation (AF). Purpose Whether exposure to commonly-used pesticides triggers AF if so, explore the underlying molecular mechanism. Methods Ten commonly used pesticides in the Netherlands, including glyphosate, MCPA and boscalid, were used to study cardiotoxicity using experimental Drosophila and rat model systems for AF. Drosophila were exposed to three varying pesticide concentrations, ranging from reported environment concentrations, LD50 and high dose, followed by survival and heart wall measurements (heart rate (HR) and arrhythmicity index). In addition, rats were exposed to four pesticides, paraquat, glyphosate, round-up and MCPA for 16 months followed by AF detection (ECG) and Westernblot and metabolomic analyses of the atrial tissue samples. Results A dose dependant survival curve was observed of Drosophila fed with pesticides compared to controls. In prepupae a significant reduction in HR and increase in arrhythmicity index was found for all? utilized pesticides. Furthermore, a significant increase in AF and atrial arrhythmic episodes was observed in rats treated with pesticides (15-70%) compared to non-treated control rats (0%). Metabolomic analyses in rats revealed a significant increase in mitochondrial supercomplexes and 6-phosphoglyconlactate levels in pesticide treated rats compared to controls, suggesting a role for mitochondrial and energy dysfunction to underlie pesticide-induced AF. Conclusion(s) This study provides evidence that chronic exposure to commonly-used pesticides in the Netherlands affects longevity, heart wall function in Drosophila and triggers atrial arrhythmia and AF in rats. Likely, the pesticides impair mitochondrial function and energy metabolism.