Oxidative stress-mediated mitochondrial pathway-dependent apoptosis is induced by silica nanoparticles in <i>H9c2</i> cardiomyocytes

Abstract

The use of silica nanoparticles (SiNPs) is increasing in popularity; however, the emissions released during manufacturing, use and during the disposal stages potentially harm the environment. SiNPs can enter the body and cause cardiac toxicity indirectly or directly. However, toxicological data on SiNPs in cardiac cells <i>in vitro</i>, and the detailed molecular mechanisms by which damage is caused remain unclear. In the present study, oxidative stress-mediated apoptosis and cytotoxicity induced by SiNPs in <i>H9c2</i> cells were examined. <i>H9c2</i> cells were used to explore the mechanisms of toxicity by treating cells with 0, 25, 50, 100, and 200 µg/ml SiNPs, with and without 3 mM of the reactive oxygen species (ROS) scavenger, N-acetyl-l-cysteine (NAC), for 24 h. The results showed that SiNPs decreased cell viability and proliferation by increasing the release of lactate dehydrogenase (LDH) and inducing apoptosis in <i>H9c2</i> cells. ROS levels were significantly increased in a dose-dependent manner. Additionally, the levels of superoxide dismutase (SOD), glutathione (GSH), and GSH-peroxidase (Px) were significantly decreased following exposure to SiNPs. Treatment with NAC attenuated LDH release; the levels of ROS, SOD, GSH, and GSH-Px production were increased, and SiNPs-induced mitochondrial pathway-dependent apoptosis was reduced. These results demonstrate that apoptosis and cytotoxicity induced by SiNPs in <i>H9c2</i> cells are a result of ROS-mediated oxidative stress. These data suggest that exposure to SiNPs is a potential risk factor for cardiovascular disease.