| Objective:Graphene oxide has been a new kind of nanometer material which has excellent photo thermal properties like graphene,besides,it has good water solubility and is easy to connect with many functional groups that their own internal contains a large number of oxygen containing groups and active sites.At present,graphene oxide has been applied to the light,electricity,chemical energy,catalytic domain and biological field.In biological field,it is applied to photo thermal therapy, drug delivery, biological assay and so on widely.With the development of study in application of graphene oxide,the study on the biological safety of graphene oxide is still relatively scarce. In this study, we used a disposable tail vein injection of nano graphene oxide, to observe its effect on the pathological and biochemical function of mice,and provide a basis for the application of nano graphene oxide in the field of biological safety. Methods:ICR mice were selected with 10 rats in each group, half male and half female, they were injected with the doses of 16,8,4,2,1 mg/kg of GO solution. LD50 was calculated according to the modified Karber’s method.ICR mice were selected,half male and half female, a total of 80,weight(18 ± 2) g,which were randomly divided into 4 groups,20 mice in each group. Mice were divided into control group(distilled water), low dose group(0.35 mg / kg,1/16 LD50), middle dose group(0.7 mg / kg and 1/8 LD50) and high dose group(1.4 mg / kg and 1 / 4 LD50).We used single tail vein injection,the injection volume of 10 ml / kg, injection speed 0.02-0.03 ml/s. At Day 3 and Day 15 after injection,mice were sacrificed by cervical dislocation and take the heart and make pathological section;make the myocardium grind homogenate.Then the myocardial enzyme such as AST、LDH、Na+,K+-ATPase、Ca2+,Mg2+-ATPase and antioxidant indicators such as MDA、SOD、GSH-Px、T-AOC were measured. Results: 1 Result of acute toxicityThe LD50 of GO in mice was 5.657 mg/kg and brown granular material was observed in myocardial blood vessels in the dose of 16 mg/kg. 2 Changes in body weight and behaviorAfter injection,high dose group appeared tremor and postural instability and occasionally in situ flip in about 5 minutes, they need a long time to return to a normal state. Middle dose GO group showed gait instability and was slow reponse in 10-20 minutes after injection,they need a relatively long time to return to a normal state. Low dose GO group appeared after the injection reaction is slow, need a short time to return to a normal state. Control group after the injection is no exception.At Day 3 and Day 15,the weight of each groups were no statistically significant. At Day 3, organ coefficient of middle and high dose GO groups were significantly lower than that of the control group in both male and female(P < 0.05). 3 Results of lipid peroxidationMDA content gradually increased at Day 3 in the female and male of each dose GO groups were significantly higher than that of control group(P < 0.05), and the contents in female showed a dose effect relationship;At Day 15 after injection, MDA content in female and male of high dose GO group was significantly higher than that of the control group(P < 0.05). At Day 3 after injection, T-SOD activity in female and male of each dose GO groups were significantly higher than that of the control group(P < 0.05); at Day 15 after injection, the activity in male of each dose GO groups were statistically significant(P < 0.05) and the activity rised in female of each dose groups and it showed a dose effect relationship(P < 0.05). At Day 3 and Day 15 after injection,GSH-Px activity in female and male of each dose GO groups were significantly lower than that of the control group(P < 0.05), activity in male of high dose GO group was lower than that of the low and medium dose GO groups(P < 0.05). At Day 3 after injection, T-AOC activity in female of each GO groups had no statistical significance(P > 0.05), activity of high dose GO group in male was lower than that of the other dose GO groups(P < 0.05); at Day 15 after injection, T-AOC activity in male of high dose GO group was significantly lower than that of the control and low dose GO groups(P < 0.05), activity in female of each dose GO groups were lower than that of control group(P < 0.05). 4 Results of myocardial enzyme actionAt Day 3 after injection, AST activity in female and male was not statistically significant(P > 0.05);at Day 15 after injection, the female and male in each dose groups were significantly lower than that of the control group(P < 0.05), activity in male of high dose group was significantly lower than that of middle and low dose GO groups,it in female of high dose GO group was significantly lower than that of low dose GO group(P < 0.05). At Day 3 after injection, LDH activity in male of each dose groups were significantly lower than that of the control group(P < 0.05), activity in female of high dose GO group was significantly lower than that of the control group and low dose GO group. At Day 15 after injection, activity in male of high dose GO group was significantly lower than that of the middle and low dose GO groups(P < 0.05),activity in female of middle and high dose GO group was significantly lower than that of the control and low dose GO groups(P < 0.05). At Day 3 after injection, Na+,K+-ATPase activity in male of each groups were significantly lower than that of the control group(P < 0.05),activity in female of high dose GO group were significantly higher than that of the low dose GO group and the control group(P < 0.05); At Day 15 after injection, activity in male and female of each dose GO groups were lower than that of the control group(P < 0.05), and it of high dose GO group was lower than that of middle and low dose GOgroups(P < 0.05). At Day 3 after injection, Ca2+,Mg2+-ATPase activity in male of high dose GO group was significantly higher than that of low dose GO group and the control group(P < 0.05), activity in female of each dose GO groups were significantly higher than that of the control group(P < 0.05),besides,it of high dose GO group was higher than that of middle and low dose GO groups(P < 0.05); At Day 15 after injection, Ca2+, Mg2+-ATPase activity in male and female of each dose GO groups were significantly lower than that of the control group(P < 0.05), and it showed dose effect relationship in male, the activity in female of high dose GO group was significantly lower than that of low dose GO group(P < 0.05). 5 Results of pathological examinationDay 3 and Day 5 after injection,no myocardial pathological changes were observed in the groups in both male and female. Conclusion:The LD50 of GO by tail injection in mice was 5.657 mg/kg.The disposable tail vein injection of unmodified nano graphene oxide particles can affect the content of MDA in mouse myocardium and interfered activities of SOD, GSH-Px, T-AOC and so on which belongs to antioxidant systems and the activities of AST, LDH, Na+,K+-ATPase, Ca2+, Mg2+-ATPase and so on which is cardiac enzymes. |
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