{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:26:26Z","timestamp":1777418786571,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:00:00Z","timestamp":1410825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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 <jats:italic>in vitro<\/jats:italic> study in which 80\u2010nm HA NPs were incubated with normal Buffalo rat liver (BRL) cells. By analyzing the changes in cell viability, apoptosis\/necrosis and the mitogen\u2010activated 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 <jats:italic>in vivo<\/jats:italic> 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\u2009\u00b5g\u2009ml<jats:sup>\u22121<\/jats:sup> 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\u2010dependent manner. Moreover, our <jats:italic>in vivo<\/jats:italic> study indicated that HA NPs increased the white blood cell count (WBC) and the levels of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), 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 (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) and malondialdehyde (MDA). These data demonstrate that at certain concentrations, 80\u2010nm HA NPs cause hepatotoxicity and liver injury. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3073","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T06:45:59Z","timestamp":1410849959000},"page":"1256-1264","source":"Crossref","is-referenced-by-count":24,"title":["Hepatotoxicity and liver injury induced by hydroxyapatite nanoparticles"],"prefix":"10.1002","volume":"34","author":[{"given":"Qingqing","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Biomaterials Research &amp; Testing Center,Shanghai Key Laboratory of Stomatology, Ninth People's Hospital Shanghai Jiaotong University School of Medicine  Shanghai 200023 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xue","sequence":"additional","affiliation":[{"name":"Shanghai Biomaterials Research &amp; Testing Center,Shanghai Key Laboratory of Stomatology, Ninth People's Hospital Shanghai Jiaotong University School of Medicine  Shanghai 200023 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Biomaterials Research &amp; Testing Center,Shanghai Key Laboratory of Stomatology, Ninth People's Hospital Shanghai Jiaotong University School of Medicine  Shanghai 200023 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-10-133"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065000"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2013.02.005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.07.034"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50233"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.05.035"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2008.04.015"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-007-3039-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/69.2.424"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.06.097"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.30755"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.07.069"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1088\/0957-4484\/22\/5\/055101"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2003.10.081"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2009.02.005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/17435390.2010.507316"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2nr31785k"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20762"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-012-0705-6"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31892"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1166\/jnn.2011.3956"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2nr00044j"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2010.09.009"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11051-011-0671-x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2011.04.034"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.02.007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.1745"},{"key":"e_1_2_7_29_1","first-page":"2891","article-title":"SiO2 nanoparticle\u2010induced impairment of mitochondrial energy metabolism in hepatocytes directly and through a Kupffer cell\u2010mediated pathway in vitro","volume":"9","author":"Xue Y","year":"2014","journal-title":"Int. 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