title: Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo.
abstract: Silica nanoparticles (SiO2 NPs) have been shown to exert cytotoxic effects in hepato-cytes 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.
authors.affiliation: Shanghai 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 China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Xue
authors.forename: Jiao
authors.initials: J
authors.lastname: Sun
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016018:Least-Squares Analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011915:Rats, Inbred BUF; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D017077:Culture Media, Conditioned; D009569:Nitric Oxide; D012822:Silicon Dioxide
keywords: Kupffer cells; coculture; hepatic injury; metabolomics; oxidative stress; silica nanoparticles