Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca^sup 2+^ handling in adult rat cardiomyocytes

• Published in: American journal of physiology. Heart and circulatory physiology 2017-04, Vol.312 (4), p.H645
• Main Authors: Guerrero-Beltrán, Carlos Enrique, Bernal-Ramírez, Judith, Lozano, Omar, Oropeza-Almazán, Yuriana, Castillo, Elena Cristina, Garza, Jesús Roberto, García, Noemí, Vela, Jorge, García-García, Alejandra, Ortega, Eduardo, Torre-Amione, Guillermo, Ornelas-Soto, Nancy, García-Rivas, Gerardo
• Format: Article
• Language: English
• Subjects: Apoptosis; Calcium; Cardiomyocytes; Health risk assessment; Nanoparticles; Toxicity
• ISSN: 0363-6135; 1522-1539

Recent evidence has shown that nanoparticles that have been used to improve or create new functional properties for common products may pose potential risks to human health. Silicon dioxide (SiO2) has emerged as a promising therapy vector for the heart. However, its potential toxicity and mechanisms of damage remain poorly understood. This study provides the first exploration of SiO2-induced toxicity in cultured cardiomyocytes exposed to 7- or 670-nm SiO2 particles. We evaluated the mechanism of cell death in isolated adult cardiomyocytes exposed to 24-h incubation. The SiO2 cell membrane association and internalization were analyzed. SiO2 showed a dose-dependent cytotoxic effect with a half-maximal inhibitory concentration for the 7 nm (99.5 ± 12.4 μg/ml) and 670 nm (>1,500 μg/ml) particles, which indicates size-dependent toxicity. We evaluated cardiomyocyte shortening and intracellular Ca2+ handling, which showed impaired contractility and intracellular Ca2+ transient amplitude during β-adrenergic stimulation in SiO2 treatment. The time to 50% Ca2+ decay increased 39%, and the Ca2+ spark frequency and amplitude decreased by 35 and 21%, respectively, which suggest a reduction in sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Moreover, SiO2 treatment depolarized the mitochondrial membrane potential and decreased ATP production by 55%. Notable glutathione depletion and H2O2 generation were also observed. These data indicate that SiO2 increases oxidative stress, which leads to mitochondrial dysfunction and low energy status; these underlie reduced SERCA activity, shortened Ca2+ release, and reduced cell shortening. This mechanism of SiO2 cardiotoxicity potentially plays an important role in the pathophysiology mechanism of heart failure, arrhythmias, and sudden death.