Cardiotoxicity of the diamide insecticide chlorantraniliprole in the intact heart and in isolated cardiomyocytes from the honey bee

Abstract

In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca2+ release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1–10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca2+ channels responsible for the cardiac action potentials depolarization phase. Two types of Ca2+ currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca2+ currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.

Chlorantraniliprole Formulation Poisoning: A Signal for Cardiac Conduction Abnormalities

“…Experimental data in honey bees demonstrate chlorantraniliprole‐associated cardiac rhythm disturbances including bradycardia and cardiac arrest in isolated bee hearts [ 7 ]. Extrapolation of these findings to human electrophysiology is substantially limited by phylogenetic and physiological differences, and this evidence is cited only to illustrate that insect cardiac tissue can be affected; it does not validate a human mechanistic inference.…”

Chlorantraniliprole Formulation Poisoning: A Signal for Cardiac Conduction Abnormalities

“…Experimental data in honey bees demonstrate chlorantraniliprole‐associated cardiac rhythm disturbances including bradycardia and cardiac arrest in isolated bee hearts [ 7 ]. Extrapolation of these findings to human electrophysiology is substantially limited by phylogenetic and physiological differences, and this evidence is cited only to illustrate that insect cardiac tissue can be affected; it does not validate a human mechanistic inference.…”

Can Cyantraniliprole Affect the Cardiovascular System of Male Wistar Rats Maternally Exposed During Pregnancy and Lactation?

“…Cardiovascular evaluations of offspring exposed to maternal CYA revealed no changes in heart rate or blood pressure at puberty or adulthood for both tested doses. A study evaluating the effects of chlorantraniliprole on bee cardiomyocytes showed that this agrochemical may cause alterations in electrophysiology and calcium homeostasis in these cells but did not relate this to possible effects in mammals [31]. Also, this compound has been shown to reduce heart weight in male Sprague-Dawley rats [29].…”

Chlorantraniliprole Formulation Poisoning: A Signal for Cardiac Conduction Abnormalities

“…Experimental data in honey bees demonstrate chlorantraniliprole‐associated cardiac rhythm disturbances including bradycardia and cardiac arrest in isolated bee hearts [ 7 ]. Extrapolation of these findings to human electrophysiology is substantially limited by phylogenetic and physiological differences, and this evidence is cited only to illustrate that insect cardiac tissue can be affected; it does not validate a human mechanistic inference.…”

Can Cyantraniliprole Affect the Cardiovascular System of Male Wistar Rats Maternally Exposed During Pregnancy and Lactation?

“…Cardiovascular evaluations of offspring exposed to maternal CYA revealed no changes in heart rate or blood pressure at puberty or adulthood for both tested doses. A study evaluating the effects of chlorantraniliprole on bee cardiomyocytes showed that this agrochemical may cause alterations in electrophysiology and calcium homeostasis in these cells but did not relate this to possible effects in mammals [31]. Also, this compound has been shown to reduce heart weight in male Sprague-Dawley rats [29].…”

Chlorantraniliprole Formulation Poisoning: A Signal for Cardiac Conduction Abnormalities

“…Experimental data in honey bees demonstrate chlorantraniliprole‐associated cardiac rhythm disturbances including bradycardia and cardiac arrest in isolated bee hearts [ 7 ]. Extrapolation of these findings to human electrophysiology is substantially limited by phylogenetic and physiological differences, and this evidence is cited only to illustrate that insect cardiac tissue can be affected; it does not validate a human mechanistic inference.…”

Can Cyantraniliprole Affect the Cardiovascular System of Male Wistar Rats Maternally Exposed During Pregnancy and Lactation?

“…Cardiovascular evaluations of offspring exposed to maternal CYA revealed no changes in heart rate or blood pressure at puberty or adulthood for both tested doses. A study evaluating the effects of chlorantraniliprole on bee cardiomyocytes showed that this agrochemical may cause alterations in electrophysiology and calcium homeostasis in these cells but did not relate this to possible effects in mammals [31]. Also, this compound has been shown to reduce heart weight in male Sprague-Dawley rats [29].…”