Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo

Abstract

Silica nanoparticles (SiO 2 NPs) have been shown to exert cytotoxic effects in hepatocytes and to cause liver injury. In the liver, Kupffer cells (KCs), as the resident macrophages, play an important role in the normal physiology and homeostasis of the liver. Nevertheless, few studies have attempted to clarify the role of KCs in hepatic injury induced by SiO 2 NPs. In this study, we treated Buffalo rat liver (BRL) cells with the supernatants of SiO 2 NP-stimulated KCs to determine KC-mediated hepatotoxicity and its underlying preliminary mechanism. We also examined the response of KCs and liver injury in vivo after the administration of SiO 2 NPs. The results showed that KCs stimulated by SiO 2 NPs release large amounts of reactive oxygen species, tumor necrosis factor-α and nitric oxide. After BRL cells were cultured with the supernatants of SiO 2 NP-stimulated KCs, the viability of BRL cells was reduced, and increases in aspartate aminotransferase and lactate dehydrogenase leakage were observed. Exposure to SiO 2 NPs in vivo caused KC hyperplasia, hepatic inflammation, and oxidative stress, which led to changes in the biochemical composition of the liver. These data suggest that SiO 2 NPs activate KCs to mediate hepatic injury and that the preliminary mechanism involves the release of bioactive substances from KCs.

Proposing Urothelial and Muscle In Vitro Cell Models as a Novel Approach for Assessment of Long-Term Toxicity of Nanoparticles

“…The transient increase in ROS levels and activation of Nrf2 transcription factor for TiO 2 and to a lesser extent PAA correlates with the highest cytotoxicity of these two NPs and is in agreement with other studies, where it has been shown that TiO 2 and iron oxide NPs can induce apoptosis and other changes in vitro through ROS-mediated mechanisms [ 73 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. Furthermore, mild oxidative stress activates phase II antioxidant enzymes through the activation of Nrf2 transcription factor, while high levels of ROS overwhelm a cell’s protective mechanisms and cause cell dysfunction and cell death [ 75 ].…”

A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

“…Further, KCs stimulated with NMs secreted significant quantities of the pro-inflammatory cytokine TNF-α. Chen, Xue, and Sun (2013) also showed that supernatants of the KCs stimulated with SiO 2 NMs, subsequently reduced cellular viability in BRL cells.…”

“…Further, buffalo rat liver (BRL) cells were treated with supernatants derived from SiO 2 NM-stimulated KCs (isolated primary cells) (in vitro 24 hr exposure at a concentration range of 100-800 μg/ml) to determine KC-mediated hepatotoxicity. Chen, Xue, and Sun (2013) showed as compared with control NMs-induced inflammatory cell infiltration at the portal regions of the liver. In addition, exposure of rats to SiO 2 NMs for 48 hr resulted in a significant rise in the number of KCs in the tissue.…”

Review of toxicological effect of quantum dots on the liver

“…The QDs entered the liver through the venous pathway and then first came into contact with macrophages and sinusoidal endothelial cells in the liver (Liang et al, 2015). Kupffer cells play a very important role in mediating the liver toxicity of QDs, and the intake of QDs in to Kupffer cells will greatly affect the toxic effects of QDs on other hepatocytes (Chen, Xue, & Sun, 2013;Fischer et al, 2010;Liang et al, 2015;Zhu et al, 2017). The Liang et al study showed that CdTe/CdS-MSA QDs mainly accumulated in the liver sinusoids and were selectively taken up by Kupffer cells and liver sinusoidal endothelial cells instead of by hepatocytes within 3 h (Liang et al, 2015).…”