title: Hepatotoxicity and liver injury induced by hydroxyapatite nanoparticles.
abstract: As hydroxyapatite nanoparticles (HA NPs) are increasingly used in biomedical and biotechnological fields, risk assessment of HA NPs has attracted extensive attention. Nevertheless, little is known about the potential adverse effects of HA NPs on normal hepatocytes and the liver. In the present study, we conducted an in vitro study in which 80-nm HA NPs were incubated with normal Buffalo rat liver (BRL) cells. By analyzing the changes in cell viability, apoptosis/necrosis and the mitogen-activated protein kinase (MAPK) signaling pathway, we investigated the cytotoxicity and potential mechanism of HA NPs in hepatocytes. Furthermore, we used the serum hematology and histopathology examinations to explore the in vivo effects of HA NPs on the structure and function of the liver. Our results showed that exposure to HA NPs at a concentration above 200 µg ml(-1) decreased cell viability, increased levels of lactate dehydrogenase (LDH) leakage, induced apoptosis and necrosis, and triggered the MAPK signaling pathway in BRL cells in a dose-dependent manner. Moreover, our in vivo study indicated that HA NPs increased the white blood cell count (WBC) and the levels of tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum, caused inflammatory cell infiltration at the portal area in the liver, and induced hepatic oxidative stress with elevated levels of hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA). These data demonstrate that at certain concentrations, 80-nm HA NPs cause hepatotoxicity and liver injury.
authors.affiliation: Shanghai Biomaterials Research & Testing Center,Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200023, 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: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D017886:Durapatite / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D017886:Durapatite; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020928:Mitogen-Activated Protein Kinases
keywords: MAPK; hepatotoxicity; hydroxyapatite nanoparticles; liver; oxidative stress