Journal Article

Cobalt oxide nanoparticles induce oxidative stress and alter electromechanical function in rat ventricular myocytes

Corradini, Emilia, Pinelli, Silvana, Zaniboni, Massimiliano, Cacciani, Francesca, Montalbano, Serena, Quaini, Federico, Ruotolo, Roberta, Galati, Serena, Stilli, Donatella, Savi, Monia, Vilella, Rocchina, Perotti, Alessio, Frati, Caterina, Buschini, Annamaria, Bocchi, Leonardo

2021

Overview

Background Nanotoxicology is an increasingly relevant field and sound paradigms on how inhaled nanoparticles (NPs) interact with organs at the cellular level, causing harmful conditions, have yet to be established. This is particularly true in the case of the cardiovascular system, where experimental and clinical evidence shows morphological and functional damage associated with NP exposure. Giving the increasing interest on cobalt oxide (Co 3 O 4 ) NPs applications in industrial and bio-medical fields, a detailed knowledge of the involved toxicological effects is required, in view of assessing health risk for subjects/workers daily exposed to nanomaterials. Specifically, it is of interest to evaluate whether NPs enter cardiac cells and interact with cell function. We addressed this issue by investigating the effect of acute exposure to Co 3 O 4 -NPs on excitation-contraction coupling in freshly isolated rat ventricular myocytes. Results Patch clamp analysis showed instability of resting membrane potential, decrease in membrane electrical capacitance, and dose-dependent decrease in action potential duration in cardiomyocytes acutely exposed to Co 3 O 4 -NPs. Motion detection and intracellular calcium fluorescence highlighted a parallel impairment of cell contractility in comparison with controls. Specifically, NP-treated cardiomyocytes exhibited a dose-dependent decrease in the fraction of shortening and in the maximal rate of shortening and re-lengthening, as well as a less efficient cytosolic calcium clearing and an increased tendency to develop spontaneous twitches. In addition, treatment with Co 3 O 4 -NPs strongly increased ROS accumulation and induced nuclear DNA damage in a dose dependent manner. Finally, transmission electron microscopy analysis demonstrated that acute exposure did lead to cellular internalization of NPs. Conclusions Taken together, our observations indicate that Co 3 O 4 -NPs alter cardiomyocyte electromechanical efficiency and intracellular calcium handling, and induce ROS production resulting in oxidative stress that can be related to DNA damage and adverse effects on cardiomyocyte functionality.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Action potential / Biomedical and Life Sciences / Biomedicine / Calcium / Calcium (intracellular) / Cardiac arrhythmia / Cardiac EC coupling / Cardiac function / Cardiac muscle / Cardiomyocytes / Cardiomyopathy / Cardiovascular diseases / Cardiovascular system / Causes of / Cobalt / Cobalt oxide nanoparticles / Cobalt oxides / Contraction / Damage accumulation / Deoxyribonucleic acid / Development and progression / DNA / DNA damage / Environmental Health / Excitation-contraction coupling / Exposure / Fluorescence / Genotoxicity / Health aspects / Health risks / Heart / Heart failure / Industrial applications / Internalization / Intracellular / Intracellular calcium dynamics / Medical equipment / Membrane potential / Membranes / Motion detection / Motion perception / Muscle contraction / Myocytes / Nanomaterials / Nanoparticles / Nanotechnology / Nanotoxicology / Occupational exposure / Organs / Oxidative stress / Pharmacology/Toxicology / Physiological aspects / Pneumology/Respiratory System / Public Health / Risk factors / ROS production / Stability analysis / Transmission electron microscopy / Ventricle / Ventricular function