Spleen injury and apoptotic pathway in mice caused by titanium dioxide nanoparticules.
Nanoparticulate titanium dioxide (TiO(2)) has been demonstrated to decrease immunity of mice, but very little is known about the injury of spleen involved immunomodulation and its molecular mechanism. In order to understand the spleen injury induced by intraperitoneal injection of TiO(2) nanoparticules (NPs) for consecutive 45 days, the spleen pathological changes, apoptosis, the expression levels of the apoptotic genes and their proteins, and oxidative stress in the mouse spleen were investigated. The results demonstrated that TiO(2) NPs had obvious accumulation in the mouse spleen, leading to congestion and lymph nodule proliferation of spleen tissue, and splenocyte apoptosis. TiO(2) NPs effectively activated caspase-3 and -9, decreased the Bcl-2 the levels of gene and protein, and increase the levels of Bax, and cytochrome c genes and their protein expression, promoted ROS accumulation. Taken together, this study indicated that TiO(2) NPs-induced apoptosis in the mouse splenocyte via mitochondrial-mediated pathway. These findings provide strong evidence that the TiO(2) NPs can induce the spleen pathological changes, apoptosis, leading to the reduction of immunity of mice.
Li
Na
N
Medical College, Soochow University, Suzhou 215123, People's Republic of China.
Duan
Yanmei
Y
Hong
Mengmeng
M
Zheng
Lei
L
Fei
Min
M
Zhao
Xiaoyang
X
Wang
Jue
J
Cui
Yaling
Y
Liu
Huiting
H
Cai
Jingwei
J
Gong
Songjie
S
Wang
Han
H
Hong
Fashui
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D008813:Mice, Inbred ICR; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014025:Titanium / Q000633:toxicity*
D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium; D053148:Caspase 3; D053453:Caspase 9