| Recent years, with the rapid development of nanoscience and nanotechnology, engineered nanoparticles have been widely used and the exposed change of people to various kinds f manufactured nanoparticles will increase more and more.As the nanomaterials have some unique physical and chemical properties, such as small-scale effect, surface effect, quantum size effect and macroscopic quantum tunneling effect, their access to the ecological environment or organisms may lead to special biological effects, and then cause negative impact on environment and human health. Therefore, the biological safety of nanomaterials issue received extensive attention. As the wide range and different chemical properties of nano-materials, people's understanding of the toxic effects and safety evaluation of nanomaterials is still quite limited.This project has chosed two kinds of most widely used nanomaterials: nano-silica (SiO2) and carbon nanotubes, to study their toxic effects to animal.Nano-scale SiO2 is currently the world's most productive industrial production of nano-powder materials, its products have been widely used in chemical materials and biological medicine. Micron crystalline SiO2 represented by quartz has been shown does harm to the human body. So the safety of nano- SiO2 is also attracted attention,At present, the biological safety research of nano- SiO2 mainly focused on the respiratory system as a whole and cell toxicity effect, while the reports of its harm to the reproductive function is few.Carbon nanotubes (CNTs) were the first large-scale industrial production of nano-materials and have also been widely used in bio-medicine areas of daily life. The toxic effect of CNTs is more comprehensive and in-depth, but the study on the toxic effects of CNTs using metabonomics is rarely reported.In the first part, we studied the damage effects of nano- SiO2 on male rats` reproductive function, and compared with micron SiO2 particle size, investigating impact of particle size to the toxic effects; in the second part, we studied the Effect of CNTs on liver and kidney function and its mechanism by metabonomic approach. The reproductive damage of male rats induced by nano-silicaIn order to study the reproductive toxicity of nano-silica, male Wistar rats were exposed to nano-silica and micro silica by intratracheal injection once two days. Rats were killed after 5 week's exposure. 30 male Wistar rats were divided into 5 groups randomly,the dose group( 227.5 mg / kg BW), the low dose group (1.5 mg / kg BW)and control group(0.9% NaCl solution) respectively, per group has 6 rats.(1) The sperm of epididymis were observed. The results showed that in the epididymis, comparing to the control group, nm- SiO2 and high doseμm- SiO2 group sperm count and the rate of sperm mobility were decreased significantly, and the rate of malformation was raised in different extent.(2) Pathology examination on lung tissue and testis tissue. The observations of lung tissue indicated matrix inflammation in lung tissue after exposure. Testis tissue had no obvious change.(3) The levels of biochemical marker enzyme of testis and serum were detected, and the levels of gonadal hormone in serum were also detected. After exposure, the level of testosterone (T) in high dose groups decreased both in serum and testis. The level of follicle stimulating hormone (FSH) was raised in serum in the high dose groups and the level of LH had no significant change in all experimental groups. Meanwhile, the testicular function mark enzyme: lactic dehydrogenase (LDH) and succinate dehydrogenase (SDH) activity were decreased in nano- SiO2 group. Suggesting that exposure affected the sperm function.(4) The indications of oxidative damage were detected on testicular tissue and serum of rats. In this study, the level of MDA was increased; the activities of superoxide dismutase (SOD) and glutathioneperoxidase (GSH-Px) were decreased.(5) Flow cytometry (FCM) was applied to analyze the spermatogenic cell. The result showed that the percentage of apoptotic cells in nm- SiO2 and high doseμm- SiO2 groups were higher than that in the control group. In nm- SiO2 and high doseμm- SiO2 groups the percentage of haploid cell (1C) was lower and tetraploid cell (4C) was higher than that in the control group, respectively. The percentages of cells in G0/G1-phase in high dose nm- SiO2 andμm- SiO2 groups were lower and G2/M-phase in high dose nm-SiO2 group was higher than that in the control group.(6) The male rats were matched with normal female rats in the ratio of 1:2 after 5 weeks exposure. On the 20th day of the pregnancy, half of the female rats were sacrificed and the fetuses were observed. The young rats were observed after the childbearing of other female rats. The results showed that the embryo of pregnant rats had been affected by the exposure of SiO2. Comparing to the control group, the mating rate and the fetus count of high dose nm- SiO2 group were decreased significantly, but the fetus and young rats in experimental groups showed no significant difference compared to the control group.It can be concluded that SiO2 could damage the reproductive system of male rats, nano- SiO2 showed the tendency of higher toxicity than micro- SiO2.Effect of CNTs on liver and kidney function of rat by metabonomic approachIn order to study the Effect of CNTs on liver and kidney function, male 24 male Wistar rats were divided into 4 groups randomly,the high dose group (22.5 mg / kg BW), the middle dose group (15 mg / kg BW), the low dose group (7.5 mg / kg BW) and control group (0.9 %NaCl solution) respectively. per group has 6 rats. The rats were exposed to CNTs by intratracheal injection once a day. The rats were exposed for 15 days. The biochemical effects of CNTs on rats were investigated using 1H NMR spectroscopy. The data of 1HNMR spectra were subjected to principal component analysis (PCA) or partial least square-discriminate analysis (PLS-DA).(1) The pathological changes of liver and kidney, serum biochemical indexes were detected. The level of TP and of TC in high-dose group was respectively less than that of control group. The results of pathological analysis indicated that there were small amounts inflammatory cell infiltration and hepatic cell adipose degeneration in the liver of rats in high-dose group; kidney had not been found obvious change.(2) The effects of CNTs on metabolic profiles of urine were investigated. The results showed that the levels of acetic acid, succinic acid, citric acid, trimethylamine oxide and other substances were significantly changed.(3) The effects of CNTs on metabolic profiles of plasma samples were investigated. The results showed that the levels of lactic acid, lipoprotein, amino acids, glucose, and VLDL and LDL content of such material were significantly changed.(4) The effects of CNTs on metabolic profiles of liver tissue were investigated. The results showed that the levels of lactic acid, glucose, fatty substances were significantly changed.(5) The effects of CNTs on metabolic profiles of kidney tissue were investigated. The results showed that the levels of trimethylamine oxide, lactate, glucose, fatty substances were significantly changed.Metabonomic analysis indicated that CNTs can induce changes in endogenous metabolic profiles. The disturbation of the energy metabolism and fat metabolism maybe an important event in the duration of the hepatotoxicity and nephrotoxicity induced by CNTs.
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