| Objective: To study the effects of two ferroferric oxide nanoparticles(nano-Fe3O4) with different sizes on mice after intravenous administration. The nano-Fe3O4 induced changes in liver and kidney functions were compared, as well as provide the reference materials for the bio-safety evaluation of it. Methods:1. Eighty-one male CD-1(ICR) mice(6 ~ 8 weeks old) were randomly assigned to three treatments. and intravenously injected with ultrapure water(control), 6.3 nm nano-Fe3O4(6.3-Fe3O4 treatment) and 54.6 nm nano-Fe3O4(54.6-Fe3O4 treatment), respectively. The mice exposed to two types of nano-Fe3O4 nanoparticles were given a single dose of 10 mg/kg body weight, and sacrificed at 1, 3 and 7 days post-exposure, respectively.2. After sacrifice, serum was collected from each mice for the analysis of liver and kidney functions by automatic biochemical analyzer. The liver and kidneys were quickly isolated, and then the organ coefficient was calculated. The distribution of nano-Fe3O4 in liver and kidney was observed using TEM. The pathological changes of liver and kidney were observed with a light microscope after hematoxylin-eosin(HE) staining. The apoptosis was evaluated by TUNEL assay. The GSH, SOD, GSH-Px, CAT and MDA levels in liver and kidney were determined according to the kit instructions. Results:1. For each test time point, the treatments showed no obvious differences compared with the control group, and no significant differences were observed in the liver viscera coefficient(P>0.05). There was no statistically significant difference between the mice exposed to different nano-Fe3O4(P>0.05).2. Compared with control groups, The liver viscera coefficient of mice showed no significant difference between each group after 1-day administration(P>0.05),then went down to normal after treatment 3d and 7d;nano-Fe3O4 exposure increased the serum ALT, and AST activities after 1-day administration(P<0.01 or P<0.05). However, the serum ALT and AST levels went down to normal a 3d and 7d post-exposure; The MDA, SOD, CAT and GSH-Px levels in the liver after treatment showed no significant difference(P>0.05) after 1d, 3d, 7d. GSH levels increased significantly 1d post-exposure(P<0.05), and returned to normal later;While no obvious pathological change and apoptosis were found in the liver of mice treated with nano-Fe3O4.(3) The kidney viscera coefficient of mice showed no significant difference between each group(P>0.05); In the mice exposed to nano-Fe3O4, serum TBIL activity significantly increased after 3d(P<0.05), and gradually returned to normal after 7 d. IBIL and UA levels showed no significant difference after the treatment(P>0.05); there no significant difference was found in the MDA, GSH, SOD and GSH-Px levels of kidney tissues(P>0.05) after 1 d, 3 d and 7 d, but CAT level increased significantly after 1 d, 3 d, and then went down to normal level, and no difference could be observed between the two treatments(P>0.05); Pathology examination, and apoptosis detection demonstrated that nano-Fe3O4 treatments did not induce any obvious changes in the renal tissues. Conclusions:Under the experimental conditions1. The mice poisoned by intravenous injection of different size of nano-Fe3O4, nano-particles can distribute in the liver and kindey tissue of the mice.2. The oxidative damages induced by nano-Fe3O4 in 1d or 3d, and then went down to normal level in 7 day.3. Pathology examination, and apoptosis detection demonstrated that nano-Fe3O4 treatments did not induce any obvious changes in the liver and renal tissues.4. There was no statistically significant difference between the mice exposed to different nano-Fe3O4(P>0.05).This experiment, suggested that intravenous injection with a single dose of 10mg/kg body weight is relatively safe for both the nano-Fe3O4 with different sizes. |
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