| Objective: Graphene oxide(GO) is a derivative of graphene after oxidation treatment, because of its unique physical and chemical properties, it has been widely applied. Graphene oxide is mainly used for drug delivery, cancer treatment and biological sensors in medical field, with the development and application of graphene and its derivatives, a large number of it will enter the ecological environment, at present,the study about nano- graphene oxide(nano-GO)biological effects and its safety is less, the potential health and environmental risks should cause concern. In this study, through single tail vein injection of nano graphene oxide and observe the effects of various indicators on the liver of mice, to provide basis for its safety applications in clinical and other fields.Methods: Acute toxicity experiment: Total 60 ICR mice with equal males and females were randomly divided into 6 groups,each group with 10 mice. The mice were treated with nano-GO with different doses,and observed toxicity symtome and death situation.The LD50 and its 95%confident limit were calculated by Karber’s method. The effects of GO on the liver of mice:Eighty clean IC R mice were randomly divided into four groups:the control group(high purity water),the nano-GO groups exposed with different doses of 1/16 LD50, 1/8 LD50, 1/4 LD50 body weight,20 in each group,through single tail vein injection, the capacity was 10 ml /kg.Then measured the levels of ALT,AST,LDH,MDA,SOD,GSH-Px,Na+-K+-ATPase,Ca2+-Mg2+-ATPase in liver tissue and observing pathological teration after 3 days and 15 days of exposure to nano-GO respectively.Result: 1. Acute toxicity experiment The LD50 was calculated by Karber’s method.LD50 in mice with GO was 5.657mg/kg and its 95% confident limit was 3.745~7.569 mg / kg.2.The effects of GO on the liver of mice:(1) Changes in mice weight and liver organ coefficient 3 days and 15 days after the exposure, the mice weigh and liver coefficient in each exposure groups were no significant difference(P > 0.05).(2) Effects of nano-GO on the activity of ALT, AST and LDH in liver of mice 3 days after exposure, the ALT activities in mice liver of female in each exposure groups were no significant difference(P > 0.05), the LDH activities in liver of mice in 1.40 mg/kg exposure group were decreased(P < 0.05), the AST activities in liver of female mice in 1.40 mg/kg nano-GO exposure group and in liver of male mice in 0.70, 1.40 mg / kg exposure group s were decreased(P < 0.05), the ALT activities in liver of male mice in 1.40 mg / kg exposure group were decreased(P < 0.05). 15 days after Exposure, compared with the control group, the ALT activities in liver of female mice in each nano-GO exposure groups were no significant difference(P > 0.05), the AST activities in mice liver and the ALT activities in liver of male mice in 0.70、1.40 mg/kg exposure groups were decreased(P < 0.05),the LDH activities in liver of male mice in 1.40 mg/kg nano-GO exposure group were decreased(P < 0.05).(3) Effects on Lipid Peroxidation of mice liver 3 days after the exposure,the MDA contents in liver of female mice in each nano-GO exposure group were increased(P <0.05), the MDA contents in liver of male mice in 0.35 、0.70 mg / kg nano-GO exposure group were decreased(P <0.05).The SOD activities in liver of female mice in 0.35, 0.70 mg / kg nano-GO exposure group were decreased(P <0.05), the SOD activities in liver of male mice in 0.35, 0.70 mg / kg nano-GO exposure group were increased(P <0.05).The GSH-Px activities in liver of mice in each nano-GO exposure groups were increased(P <0.05). 15 days after the exposure, the MDA contents in liver of female mice in each nano-GO exposure group were no significant difference(P > 0.05). The MDA contents in liver of male mice in 1.40 mg / kg nano-GO exposure group were higher than 0.35 mg / kg nano-GO exposure group(P <0.05), compared with the control group, the SOD activities in liver of mice in nano-GO exposure groups were increased(P <0.05),the GSH-Px activities in liver of mice in 0.70,1.40 mg / kg nano-GO exposure groups were decreased(P <0.05).(4) Effects of nano-GO on the activity of ATPase in liver of mice 3 days after exposure, compared with the control group,the Na+-K+-ATPase activities in liver of female mice in 0.70、1.40 mg / kg nano-GO exposure group were decreased(P < 0.05), the Ca2+-Mg2+-ATPase activities in liver of female mice in 1.40 mg / kg nano-GO exposure group were decreased(P < 0.05), the Na+-K+-ATPase、Ca2+-Mg2+-ATPase in liver of male mice in each exposure group were decreased(P < 0.05). 15 days after exposure, compared with the control group,the Na+-K+-ATPase activities in liver of mice and the Ca2+-Mg2+-ATPase activities in liver of male mice in each dose exposure group were increased(P < 0.05),the Ca2+-Mg2+-ATPase activities in liver of female mice in 0.70、1.40 mg / kg nano-GO exposure group were increased(P < 0.05).(5) Changes in pathological of mice liver 3 days after exposure, the structural of mice liver tissue in each dose exposure were complete and liver cells arranged mild disorder, the cell swelling was widespread and the cytoplasm was pale and transparent, occasionally had the nuclei pyknosis and nuclear flake dissolved, no obvious pathological changes. 15 days after exposure, the structural of female mice liver in 1.40 mg mg/kg nano-GO exposure group and the structural of female mice liver in 0.70,1.40mg/kg nano-GO exposure groups male mice were complete,liver cells arranged mild disorder, the cell swelling was widespread and the cytoplasm was pale and transparent, occasionally had the nuclei pyknosis and nuclear flake dissolved, A small amount of inflammatory cells infiltration were in the liver of male mice,no obvious pathological changes.Conclusion: The research shown that nano-GO exposure through single tail vein injection can cause decrease of LDH activity in liver of mice,induced lipid peroxidation and interfered with the activities of SOD, GSH-Px,Na+-K+-ATPase,Ca2+-Mg2+-ATPase in mice liver,cause liver cells swelling and a small amount of inflammatory cell infiltration in mice liver.The nano-GO can effect on mice liver. |
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