Inhalation of titanium dioxide induces endoplasmic reticulum stress-mediated autophagy and inflammation in mice.

Abstract

Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreen, electronics, drug delivery systems, and diverse bio-application fields. In the workplace, the primary exposure route for TiO2 nanoparticles is inhalation through the respiratory system. Because TiO2 nanoparticles have different physiological properties, in terms of size and bioactivity, their toxic effects in the respiratory system must be determined. In this study, to determine the toxic effect of inhaled TiO2 nanoparticles in the lung and the underlying mechanism, we used a whole-body chamber inhalation system to expose A/J mice to TiO2 nanoparticles for 28 days. During the experiments, the inhaled TiO2 nanoparticles were characterized using a cascade impactor and transmission electron microscopy. After inhalation of the TiO2 nanoparticles, hyperplasia and inflammation were observed in a TiO2 dose-dependent manner. To determine the biological mechanism of the toxic response in the lung, we examined endoplasmic reticulum (ER) and mitochondria in lung. The ER and mitochondria were disrupted and dysfunctional in the TiO2-exposed lung leading to abnormal autophagy. In summary, we assessed the potential risk of TiO2 nanoparticles in the respiratory system, which contributed to our understanding of the mechanism underlining TiO2 nanoparticle toxicity in the lung.

• Authors: Kyeong-Nam Yu, Jae Hyuck Sung, Somin Lee, Ji-Eun Kim, Sanghwa Kim, Won-Young Cho, Ah Young Lee, Soo Jin Park, Joohyun Lim, Changhoon Park, Chanhee Chae, Jin Kyu Lee, Jinkyu Lee, Jun-Sung Kim, Myung-Haing Cho
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 85 Pg. 106-13 (Nov 2015) ISSN: 1873-6351 [Electronic] England
• PMID: 26253354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers
• titanium dioxide
• Titanium

Topics

• Animals
• Atmosphere Exposure Chambers
• Autophagy (drug effects)
• Biomarkers (blood)
• Dose-Response Relationship, Drug
• Endoplasmic Reticulum (drug effects, immunology, pathology, ultrastructure)
• Endoplasmic Reticulum Stress (drug effects)
• Female
• Hyperplasia
• Inhalation Exposure
• Lung (drug effects, immunology, pathology, ultrastructure)
• Male
• Metal Nanoparticles (administration & dosage, toxicity)
• Mice, Inbred A
• Microscopy, Electron, Transmission
• Mitochondria (drug effects, immunology, pathology, ultrastructure)
• Particle Size
• Pneumonia (blood, chemically induced, immunology, pathology)
• Respiratory Mucosa (drug effects, immunology, pathology, ultrastructure)
• Severity of Illness Index
• Titanium (administration & dosage, toxicity)
• Toxicity Tests, Subacute