Hepatocyte apoptosis and its molecular mechanisms in mice caused by titanium dioxide nanoparticles.
While the hepatocyte apoptosis induced by TiO(2) nanoparticles (NPs) has been demonstrated, very little is known about the molecular mechanisms underlying this mouse liver apoptosis. In order to understand the hepatocyte apoptosis induced by intragastric administration of TiO(2) NPs for consecutive 60 days, the hepatocyte apoptosis, various oxidative stress parameters and the stress-related gene expression levels were assayed for the mouse liver. 60 days of TiO(2) NPs exposure, hepatocyte apoptosis in the liver could be observed, which was followed by increased reactive oxygen species accumulation, and decreased the stress-related gene expression levels of superoxide dismutase, catalase, glutathione peroxidase, metallothionein, heat shock protein 70, glutathione S transferase, P53, and transferrin; and the significant enhancement of the cytochrome p450 1A expression level. It implied that hepatocyte apoptosis, oxidative stresses, and alteration of expression levels of the genes related with TiO(2) NPs detoxification/metabolism regulation and radical scavenging action. Therefore, the application of TiO(2) NPs and exposure effects especially on human liver for long-term and low-dose treatment should be cautious.
Cui
Yaling
Y
Medical College of Soochow University, Renai Road No. 199, Suzhou 215123, People's Republic of China.
Gong
Xiaolan
X
Duan
Yanmei
Y
Li
Na
N
Hu
Renping
R
Liu
Huiting
H
Hong
Mengmeng
M
Zhou
Min
M
Wang
Ling
L
Wang
Han
H
Hong
Fashui
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D016877:Oxidants; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000235:genetics; D017382:Reactive Oxygen Species; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects*
D001672:Biocompatible Materials; D016877:Oxidants; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D010088:Oxidoreductases