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Hepatotoxicity and liver injury induced by hydroxyapatite nanoparticles
Author(s) -
Chen Qingqing,
Xue Yang,
Sun Jiao
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3073
Subject(s) - lactate dehydrogenase , viability assay , necrosis , apoptosis , in vivo , oxidative stress , chemistry , malondialdehyde , liver injury , tumor necrosis factor alpha , pharmacology , mapk/erk pathway , hepatic stellate cell , kinase , biochemistry , medicine , biology , enzyme , microbiology and biotechnology
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 (H 2 O 2 ) and malondialdehyde (MDA). These data demonstrate that at certain concentrations, 80‐nm HA NPs cause hepatotoxicity and liver injury. Copyright © 2014 John Wiley & Sons, Ltd.