<p>Silica Nanoparticles Disturb Ion Channels and Transmembrane Potentials of Cardiomyocytes and Induce Lethal Arrhythmias in Mice</p>

Abstract

Background: The toxicity of silica nanoparticles (SiNPs) on cardiac electrophysiology has seldom been evaluated. Methods: Patch-clamp was used to investigate the acute effects of SiNP-100 (100 nm) and SiNP-20 (20 nm) on the transmembrane potentials (TMPs) and ion channels in cultured neonatal mouse ventricular myocytes. Calcium mobilization in vitro, cardiomyocyte ROS generation, and LDH leakage after exposure to SiNPs in vitro and in vivo were measured using a microplate reader. Surface electrocardiograms were recorded in adult mice to evaluate the arrhythmogenic effects of SiNPs in vivo. SiNP endocytosis was observed using transmission electron microscopy. Results: Within 30 min, both SiNPs (10 −8-10 −6 g/mL) did not affect the resting potential and I K1 channels. SiNP-100 increased the action potential amplitude (APA) and the I Na current density, but SiNP-20 decreased APA and I Na density. SiNP-100 prolonged the action potential duration (APD) and decreased the I to current density, while SiNP-20 prolonged or shortened the APD, depending on exposure concentrations and increased I to density. Both SiNPs (10 −6 g/mL) induced calcium mobilization but did not increase ROS and LDH levels and were not endocytosed within 10 min in cardiomyocytes in vitro. In vivo, SiNP-100 (4-10 mg/kg) and SiNP-20 (4-30 mg/kg) did not elevate myocardial ROS but increased LDH levels depending on dose and exposure time. The same higher dose of SiNPs (intravenously injected) induced tachyarrhythmias and lethal bradyarrhythmias within 90 min in adult mice. Conclusion: SiNPs (i) exert rapid toxic effects on the TMPs of cardiomyocytes in vitro largely owing to their direct interfering effects on the I Na and I to channels and Ca 2+ homeostasis but not I K1 channels and ROS levels, and (ii) induce tachyarrhythmias and lethal bradyarrhythmias in vivo. SiNP-100 is more toxic than SiNP-20 on cardiac electrophysiology, and the toxicity mechanism is likely more complicated in vivo.

Brain Accumulation and Toxicity Profiles of Silica Nanoparticles: The Influence of Size and Exposure Route

“…A similar concentration was also reported in the workplace air near a furnace at a facility that produces ferrosilicon containing 75% of silicon, and epidemiological examination suggested the pulmonary and systemic toxicities for production workers exposed to nanoscale silicon . Furthermore, the dosage of SiO 2 NPs used in the current study was comparable with the existing literature. − …”

Silica Nanoparticle Exposure Implicates β-Amyloid (1–42) Inbound and the Accelerating Alzheimer’s Disease Progression in Mice Overexpressing Mutated Forms of Human Amyloid Precursor Protein and Presenilin 1 Genes

“…Occupational exposure to SiNPs is mainly through the intranasal route, and biomedical applications of SiNPs (drug delivery and therapy) are mainly through the intravenous route. Here, we chose intravenous injection of SiNPs in this work and the dosage is comparable with previous studies. − After 28 continuous days of intravenous administration of SiNPs, the Aβ 1–42 level in the brains of APP/PS1 mice was elevated (Figure A). There was a significant difference in the brain level of Aβ 1–42 between control and SiNP-treated groups (*** P < 0.001).…”

Environmental Fe, Ti, Al, Cu, Hg, Bi, and Si Nanoparticles in the Atrioventricular Conduction Axis and the Associated Ultrastructural Damage in Young Urbanites: Cardiac Arrhythmias Caused by Anthropogenic, Industrial, E-Waste, and Indoor Nanoparticles

“…Highly oxidative, metal, magnetic, and environmental NPs in the AV axis set the scenario for ROS production, reactive free ions, cytoskeletal disruption, altered ion channels, abnormal gap junction protein expression, inflammation, loss of sarcomeres, disordered myofilaments, organelle damage, alterations of specific proteins related to the functional status of the cardiac conduction system including the ion channel promoter. ,, NPs are transported into the heart mainly via inhalation or ingestion [gastrointestinal (GI) tract] and transferred into the systemic circulation; as shown in our cases, NPs loaded with Hg hitchhike red blood cells (RBCs) and transfer them into myocardial endothelial cells and cardiomyocytes. , Zalups and Bridges have shown that 99% of CH 3 Hg + in blood associates with RBCs and only 1% remains in the plasma. Variables such as aerodynamic size, chemical composition, corona composition, surface charge, ferrimagnetism, and redox activity result in disruption of the heart’s electrical conduction, oxidative stress, and signaling cascades with direct and indirect effects on the cardiac structure and function. − Even NPs with seemingly harmless elements such as silica produce rapid toxic effects on the cardiomyocyte transmembrane potentials in vitro, being directly associated with detrimental effects on the I Na and I to channels and Ca 2+ homeostasis and inducing tachyarrhythmias and lethal bradyarrhythmias in vivo . Guerrero-Beltrán and co-workers reported that in vitro adult rat cardiomyocytes exposed to SiO 2 depolarized the mitochondrial membrane potential, increased oxidative stress, and produced mitochondrial dysfunction.…”