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

Abstract

Qingqing Chen, Yang Xue, Jiao SunShanghai Biomaterials Research and Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of ChinaAbstract: Silica nanoparticles (SiO2 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 SiO2 NPs. In this study, we treated Buffalo rat liver (BRL) cells with the supernatants of SiO2 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 SiO2 NPs. The results showed that KCs stimulated by SiO2 NPs release large amounts of reactive oxygen species, tumor necrosis factor-a and nitric oxide. After BRL cells were cultured with the supernatants of SiO2 NP-stimulated KCs, the viability of BRL cells was reduced, and increases in aspartate aminotransferase and lactate dehydrogenase leakage were observed. Exposure to SiO2 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 SiO2 NPs activate KCs to mediate hepatic injury and that the preliminary mechanism involves the release of bioactive substances from KCs.Keywords: silica nanoparticles, Kupffer cells, coculture, oxidative stress, metabolomics, hepatic injury