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Oxidative stress increased hepatotoxicity induced by nano‐titanium dioxide in BRL‐3A cells and Sprague–Dawley rats
Author(s) -
Sha Baoyong,
Gao Wei,
Wang Shuqi,
Gou Xingchun,
Li Wei,
Liang Xuan,
Qu Zhiguo,
Xu Feng,
Lu Tian Jian
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.2900
Subject(s) - in vivo , toxicity , oxidative stress , lactate dehydrogenase , nanotoxicology , alkaline phosphatase , chemistry , pharmacology , hepatic stellate cell , in vitro , toxicology , biochemistry , medicine , enzyme , biology , microbiology and biotechnology , organic chemistry
Extensive studies have shown that titanium dioxide (TiO 2 ) nanomaterials (NMs) can cause toxicity in vitro and in vivo under normal conditions. However, an adverse effect induced by nano‐TiO 2 in many diseased conditions, typically characterized by oxidative stress (OS), remains unknown. We investigated the toxicity of nano‐TiO 2 in rat liver cells (BRL‐3A) and Sprague–Dawley (SD) rat livers under OS conditions, which were generated using hydrogen peroxide (H 2 O 2 ) in vitro and alloxan in vivo , respectively. In vitro results showed that cell death ratios after nano‐TiO 2 exposure were significantly enhanced (up to 2.62‐fold) in BRL‐3A cells under OS conditions, compared with normal controls. Significant interactions between OS conditions and nano‐TiO 2 resulted in the rapid G0/G1 to S phase transition and G2/M arrest, which were opposite to G0/G1 phase arrest in cells after NMs exposure only. In vivo results showed that obvious pathological changes in rat livers and the increased activities of four enzymes (i.e. aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase) owing to liver damage after nano‐TiO 2 exposure under OS conditions, compared with their healthy controls. In addition, compared with increased hepatotoxicity after nano‐TiO 2 exposure, micro‐TiO 2 showed no adverse effects to cells and rat livers under OS conditions. Our results suggested that OS conditions synergistically increase nano‐TiO 2 induced toxicity in vitro and in vivo , indicating that the evaluation of nanotoxicity under OS conditions is essentially needed prior to various applications of NMs in foods, cosmetics and potential treatment of diseases. Copyright © 2013 John Wiley & Sons, Ltd.