Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL-3A cells and Sprague-Dawley rats

• Published in: Journal of applied toxicology 2014-04, Vol.34 (4), p.345-356
• Main Authors: Sha, Baoyong, Gao, Wei, Wang, Shuqi, Gou, Xingchun, Li, Wei, Liang, Xuan, Qu, Zhiguo, Xu, Feng, Lu, Tian Jian
• Format: Article
• Language: English
• Subjects: alloxan; Alloxan - administration & dosage; Alloxan - toxicity; Animals; Apoptosis; Biocompatibility; Biomarkers; cell; Cell Culture Techniques; Cell Line; Cell Survival - drug effects; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; hydrogen peroxide; Hydrogen Peroxide - administration & dosage; Hydrogen Peroxide - toxicity; Liver; Liver - cytology; Liver - drug effects; Male; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; nano-titanium dioxide; Nanocomposites; Nanomaterials; Nanoparticles - chemistry; Nanostructure; nanotoxicity; Operating systems; Oxidative stress; Oxidative Stress - drug effects; Particle Size; rat; Rats; Rats, Sprague-Dawley; Rodents; Surface Properties; Surgical implants; Titanium - administration & dosage; Titanium - toxicity; Titanium dioxide; Toxicity
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.2900

ABSTRACT Extensive studies have shown that titanium dioxide (TiO2) nanomaterials (NMs) can cause toxicity in vitro and in vivo under normal conditions. However, an adverse effect induced by nano‐TiO2 in many diseased conditions, typically characterized by oxidative stress (OS), remains unknown. We investigated the toxicity of nano‐TiO2 in rat liver cells (BRL‐3A) and Sprague–Dawley (SD) rat livers under OS conditions, which were generated using hydrogen peroxide (H2O2) in vitro and alloxan in vivo, respectively. In vitro results showed that cell death ratios after nano‐TiO2 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‐TiO2 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‐TiO2 exposure under OS conditions, compared with their healthy controls. In addition, compared with increased hepatotoxicity after nano‐TiO2 exposure, micro‐TiO2 showed no adverse effects to cells and rat livers under OS conditions. Our results suggested that OS conditions synergistically increase nano‐TiO2 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. Nanotoxicity assessment of titanium dioxide (TiO2) under oxidative stress (OS) conditions is a novel field. Compared with nanomaterials (NMs) exposure only, OS conditions and nano‐TiO2 synergistically reduced BRL‐3A cell viabilities and resulted in the rapid G0/G1 to S phase transition and G2/M arrest. Interactions between OS conditions and nano‐TiO2 induced obvious pathological changes in rat livers and enhanced the activities of liver damage biomarkers.