Studies On The Acute Damages Induced By Nano-pbo 2 Particles In Mice

Objective: With the rapid development of nanotechnology, people gradually realize the benefits of nanotechnology and its vast potential market economy, also come to realize that another new issue: whether nanotechnology present potential negative effects on human health, living environment and social safety, etc., Do the nanopaticles lead to specific biological and toxicological effects when they come into living organisms? Are these effects on life processes and human health beneficial or harmful? At present, the evaluation and research of nano-particle toxicity are far behind the development of nanotechnology and nano-product. Therefore, it is a great significant for nano-materials to conduct research on the health damage.Pb (lead, Pb) is a common environmental and occupational heavy metal toxin. Pb can cause damages of central nervous system, kidney system, hematopoietic system and the cardiovascular system. Along with the improvement of traditional lead-handling procedure, the applications of nano-lead become increasingly widespread. More and more nano-sized lead comes into environment, whhich likely impact on the environment and human health. In this study, 50nm lead dioxide served as the research object, and the damages of liver and kidney function and anti-oxidation function in mice were observed and compared with that of normal size lead dioxide. The acute damages induced by of nano-PbO2 in mice and the potential mechanism was studied. The results of our research will provide a scientific basis to reveal the toxic effects and bio-safety evaluation of nano-lead dioxide.Methods:1 Healthy Kunming mice(40 males and 40 femals; 30-35g) were randomly divided into 5 groups (16 mice per treatment group): the control group, common PbO2 group (200mg/kg), 50nmPbO2 low-dose group (50mg/kg), 50nmPbO₂ middle dose group (100mg/kg), 50nmPbO₂ high-dose group (200mg/kg). PbO₂ was administered orally in doses of 0.1 ml/10 g body weight, respectively, once a day and for 5 consecutive days.2 The lead concentrations in the serum, liver, kidney, brain (cortex, hippocampus) were measured by atomic absorption spectrophotometry3 The total bilirubin levels, GOT activity, GPT activity, Cr and BUN levels in serum were measured to evaluate the liver and kidney function.4 Measurement of oxidative stress state after lead exposure in miceThe activities of anti-oxidase glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), and the levels of the lipid peroxidation (LPO) product malonaldehyde (MDA) in serum, liver, kidney and hippocampus tissue were determined by biochemical assay according to the methods described in the references using commercial kits. The levels of reactive oxygen species (ROS) in hippocampus of mice were determined by flow cytometry. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) in hippocampus of mice were determined by HPLC.Results:1 The effects of PbO₂ on the general situation of mice All mice were stay alive in each group; the body weight of individual mice was slightly reduced, but no significant difference between the treatment groups and the control group. There is no significant difference in organ coefficient of the liver, kidney and brain in each treatment group compared with the control group.2 The changes of Pb levels in serum, liver, kidney and beain The Pb levels in serum, liver, kidney, cerebral cortex and hippocampus of mice in every treatment group were significantly higher than that of the control (P<0.01), and there were good dose-response relationship between Pb concentration and the dose. At the same trearment dose, Pb concentration in liver, kidney, cerebral cortex and hippocampus of mice in nano-PbO₂ treatment group were significantly higher than that of the common PbO₂ treatment group (P <0.01). 3 The effects of PbO₂ on the liver and kidney function in mice3.1 The changes of liver function in miceThe levels of total bilirubin, GOT in serm of mice in every treatment group were significantly higher than that of the control (P<0.05, P<0.01), and there were a good dose-response relationship between Pb concentration and the Pb dose; the levels of GPT in the middle and high dose group were significantly higher than that of the control (P<0.01), but no significant differences between low dose group and the control group. At the same trearment dose, the levels of total bilirubin, GOT and GPT in serum of mice in the nano-PbO₂ treatment group were significantly higher than that of the common PbO₂ treatment group (P <0.01).3.2 The changes of renal function in miceThe levels of BUN and Creatinine in serum of mice in every treatment group were significantly higher than that of the control (P<0.05, P<0.01), and there were a good dose-response relationship between Pb concentration and the Pb dose. At the same trearment dose, the levels of BUN and Creatinine in serum of mice in the nano-PbO₂ treatment group were significantly higher than that of the common PbO₂ treatment group (P <0.01).4 The effects of PbO₂ on the oxidative stress levels in mice4.1 The changes of the MDA levels and the SOD, GSH-PX activities in serumThe MDA levels in serum of mice in every treatment group were significantly increased, while the SOD activities were significantly decreased compared with the control group (P<0.01); the GSH-PX activities in the middle and high dose group were significantly decreased compared with the control (P<0.01), but no significant differences between low dose group and the control group. There was a good dose-response relationship between the MDA levels, SOD, GSH-PX activities in serum and the Pb dose. In the nano-PbO₂ treatment group, the MDA levels were significantly lower and the SOD, GSH-PX activitied was significantly higher than that of the common PbO₂ treatment group at the same treatment dose (P <0.05, P <0.01). 4.2 The changes of the MDA levels and the SOD, GSH-PX activities in liverThe MDA levels of liver in every treatment group were significantly increased, while the SOD activities were decreased compared with the control group (P<0.01); the GSH-PX activities in the middle and high dose group were significantly decreased compared with the control (P<0.01), but no significant differences between the low dose group and the control group. There was a good dose-response relationship between the MDA levels, SOD, GSH-PX activities in liver and the Pb dose. In the nano-PbO₂ treatment group, the MDA levels were significantly lower and the SOD, GSH-PX activitied was significantly higher than that of the common PbO₂ treatment group at the same treatment dose (P <0.01).4.3 The changes of the MDA levels and the SOD, GSH-PX activities in kidneysThe MDA levels in kidney of mice in every treatment group were significantly increased, while the GSH-PX activities were decreased compared with the control group (P<0.01). However, there were no significant differences between the common PbO₂ group and the control group. The SOD activities in the middle and high dose group were significantly decreased compared with the control (P<0.01), but no significant differences between the low dose group and the control group. There was a good dose-response relationship between the MDA levels, SOD, GSH-PX activities in kindey and the Pb dose. In the nano-PbO₂ treatment group, the MDA levels were significantly lower and the SOD, GSH-PX activitied was significantly higher than that of the common PbO₂ treatment group at the same treatment dose (P <0.01).4.4 The oxidative stress in brain tissue4.4.1 The changes of the MDA levels and the SOD, GSH-PX activities in cerebral cortexThe MDA levels in cortex of mice in every treatment group were significantly increased, while the SOD and GSH-PX activities were decreased compared with the control group (P<0.01). There was a good dose-response relationship between the MDA levels, SOD, GSH-PX activities in cortex and the Pb dose. In the nano-PbO₂ treatment group, the MDA levels were significantly lower and the SOD, GSH-PX activitied was significantly higher than that of the common PbO₂ treatment group at the same treatment dose (P <0.01).4.4.2 The changes of the MDA levels and the SOD, GSH-PX activities in hippocampusThe MDA levels in hippocampus of mice in every treatment group were significantly increased, while the SOD and GSH-PX activitied were decreased compared with the control group (P<0.01), but the SOD activites were no significant differences between the common PbO₂ group and the control group. There was a good dose-response relationship between the MDA levels, SOD, GSH-PX activities in cortex and the Pb dose. In the nano-PbO₂ treatment group, the MDA levels were significantly lower and the SOD, GSH-PX activitied was significantly higher than that of the common PbO₂ treatment group at the same treatment dose (P <0.01).4.4.3 The changes of reactive oxygen species (ROS) in hippocampal cellThe ROS levels in every treatment group were significantly higher than that of the control group (P<0.01), and there was a good dose-response relationship. At the same trearment dose, the ROS levels in the nano-PbO₂ treatment group were significantly higher than that of the common PbO₂ treatment group (P <0.01).4.4.4 The changes of 8-OHdG/dG in hippocampal cellThe 8-OHdG/dG levels in every treatment group were significantly higher than that of the control group (P<0.01), and there was a good dose-response relationship. At the same trearment dose, the 8-OHdG/dG levels in the nano-PbO₂ treatment group were significantly higher than that of the common PbO₂ treatment group (P <0.01).Conclusion:1 Pb could widely distribute into the liver, kidney, brain, etc.. And the Pb levels in every tissue were increased depending on the increasing of the Pb trearment dose. At the same treatment dose, the nano-PbO₂ entered the body easily and then accumulated in the body.2 Nano-PbO₂ could damage the liver and kidney functions of mice, and the adverse effects above induced by nano-PbO₂ were distinctly stronger than that of the common PbO₂.3 Nano-PbO₂ induce the oxidative damage through the decrease of antioxidant function of the blood, liver, kidney and brain. And the oxidative damage induced by Pb was enhanced depending on the increasing of the Pb trearment dose. Tthe adverse effects above induced by nano-PbO₂ were distinctly stronger than that of the common PbO₂.