[Metabonomic study of plasma after intratracheally instilling titanium dioxide nanoparticles in rats].
OBJECTIVE
1H magnetic resonance (1H MR) spectroscopic technique in combination with pattern recognition technique were applied to analyze toxic effects of rats which were intratracheally instilled with titanium dioxide nanoparticles (nano-TiO2) as well as to detect the target organs and biomarkers associated with the toxic effects.


METHODS
Twenty-four SD male rats were divided into 4 groups randomly which were high dose group (40 mg/kg nano-TiO2), moderate dose group (4 mg/kg nano-TiO2), low dose group (0.4 mg/kg nano-TiO2) and control group (0.9% NaCl solution) respectively, there were six rats per group. All rats were exposed to the object by single intratracheally instilling at a volume of 0.1 ml/100 g. After one week observation, 1H MR spectra of plasma were measured and analyzed by principal component analysis. Histopathologic examination for tissues such as heart, lung, liver, and kidney were performed simultaneously.


RESULTS
The relative content of lactate [(37.86+/-2.58)x10(-3)], citrate [(2.21+/-0.45)x10(-3)], choline [(7.74+/-0.76)x10(-3)] and creatine [(4.17+/-1.15)x10(-3)] in high dose group were significantly decreased as compared with those [(52.07+/-5.12)x10(-3), (3.01+/-0.21)x10(-3), (9.28+/-0.78)x10(-3), (8.59+/-2.64)x10(-3)] in control group (t values were -6.024, -3.177, -3.374, -4.215 respectively, P<0.05), however the relative content of glucose [(19.41+/-1.72)x10(-3)] was significantly increased compared with that [(14.45+/-2.45)x10(-3)] in control group (t value was 2.802, P<0.05). The relative content of lactate [(44.39+/-5.09)x10(-3)] and creatine [(3.67+/-0.76)x10(-3)] in moderate group was significantly decreased compared with those [(52.07+/-5.12)x10(-3), (8.59+/-2.64)x10(-3)] in control group (t values were -3.254, -4.694 respectively, P<0.05). The relative content of pyruvate [(3.84+/-0.70)x10(-3)] was significantly increased in low dose group as compared with that [(3.13+/-0.46)x10(-3)] in control group (t value was 2.787, P<0.05), however the relative content of creatine [(8.10+/-0.72)x10(-3)] was significantly decreased compared with that [(9.28+/-0.78)x10(-3)] in control group (t value was -2.602, P<0.05). No significant difference was found between other experimental groups and control group. No visible damage was found in histopathologic examination.


CONCLUSIONS
Lung, liver, kidney and heart were the target organs of rats which were intratracheally instilling titanium dioxide nanoparticles. Lactate, pyruvate, glucose, citrate, choline and creatine can be presumed as the biomarkers when searching the target organs of the toxic effects.
Wang
Shu
S
Department of Toxicology, School of Public Health, Southeast University, Jiangsu Key Laboratory for Biomaterials and Devices, Nanjing 210009, China.
Tang
Meng
M
Zhang
Ting
T
Huang
Ming-ming
MM
Lei
Hao
H
Yang
Yang
Y
Lu
Min-yu
MY
Kong
Lu
L
Xue
Yu-ying
YY
D000818:Animals; D008297:Male; D053768:Metal Nanoparticles; D010949:Plasma / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
C009495:titanium dioxide; D014025:Titanium