Mechanisms of silver nanoparticles-induced cytotoxicity and apoptosis in rat tracheal epithelial cells

Abstract

Silver nanoparticles (AgNPs) are increasingly utilized in a number of applications. This study was designed to investigate AgNPs induced cytotoxicity, oxidative stress and apoptosis in rat tracheal epithelial cells (RTE). The RTE cells were treated with 0, 100 μg/L and 10,000 μg/L of the AgNPs with diameters of 10 nm and 100 nm for 12 hr. The cell inhibition level, apoptosis ratio, reactive oxygen species (ROS), malondialdehyde (MDA) and metallothionein (MT) content were determined. The mRNA expression of cytoc, caspase 3, and caspase 9 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we also analyzed the cytoc, caspase 3, pro-caspase 3, caspase 9, and pro-caspase 9 protein expression by western blotting. Electric cell-substrate impedance sensing (ECIS) analysis showed that the growth and proliferation of RTE cells were significantly inhibited in a dose-dependent manner under AgNPs exposure. The cell dynamic changes induced by 10 nm AgNPs were more severe than that of the 100 nm AgNPs exposure group. The intracellular MT, ROS, and MDA content increased when the exposure concentration increased and size reduced, whereas Ca 2+-ATPase activity and Na + /K +-ATPase activity changed inversely. The relative expression of protein of cytoc, caspase 3, and caspase 9 were upregulated significantly, which indicated that AgNPs induced apoptosis of RTE cells through the caspase-dependent mitochondrial pathway. Our results demonstrate that AgNPs caused obvious cytotoxicity, oxidative stress, and apoptosis in RTE cells, which promoted the releasing of cytochrome C and pro-apoptotic proteins into the cytoplasm to activate the caspase cascade and finally led to apoptosis.

Glutathione-Stabilized Silver Nanoparticles: Antibacterial Activity against Periodontal Bacteria, and Cytotoxicity and Inflammatory Response in Oral Cells

“…This was because the nanoparticles absorption by the cells gradually reaches the saturation limit, as could also be seen with cytokine release [ 55 , 56 ]. Furthermore, other authors studied the anti-proliferative activity of silver nanoparticles in two cell types, some lung fibroblasts, and observed that the uptake increase is dose-dependent [ 57 , 58 ], as shown in this study.…”

Single-Cell Analysis Reveals that Chronic Silver Nanoparticle Exposure Induces Cell Division Defects in Human Epithelial Cells

“…However, in vitro experiments looking at the effects of long-term exposure are lacking in the AgNP toxicology literature. Most in vitro studies limit AgNP exposure to 24–72 h [25,32,37,38,39,40,41,42,43,44,45], with one report extending in vitro exposure to three weeks and reporting no toxicity from AgNP exposure to human corneal epithelial cells or murine eye-associated macrophages [62]. However, in this study, only one assay, which indirectly estimated cell death, was used to assess cytotoxicity from AgNP exposure.…”

“…Particles become coated with macromolecules, such as proteins or growth factors, found in biological serum and the cell recognizes and engulfs these macromolecules, unknowingly also engulfing AgNPs. Numerous in vitro studies have shown that AgNPs can induce both cytotoxicity and genotoxicity in a variety of mammalian cells [25,32,37,38,39,40,41,42,43,44,45], as well as effects on differentiation state [46]. Specifically, there are reports of AgNP-dependent cell cycle arrest in G1 [47,48], S-phase [49,50], and at the G2/M transition [39,51].…”

<p>Comparative Assessment of Antioxidant, Anti-Diabetic and Cytotoxic Effects of Three Peel/Shell Food Waste Extract-Mediated Silver Nanoparticles</p>

“…10,46 It damages the cell barrier, inactivates ATPase activity, sensitizes cell signaling, and finally leads to apoptosis. 47 Besides, in the conventional (chemical or physical) methods of synthesis of nanoparticle, usually highly toxic chemicals are used which are highly environmentally toxic and gave rise to numerous toxic side effects upon administration, hence these are not recommended for biomedical…”