| Objective:Nanomedicine is a combination of nanometer technology and medicaltechnology. It is a new cross interdisciplinary subject, which promotes thedevelopment of medical research and clinical treatment by using thetheories and methods of nanometer materials and technology. Nanometermaterial is also the core part of nanomedicine to be realized. Grapheneoxide are highly favored and highlighted in the biomedical field for itsunique structure and physical, chemical, biological characteristics in themany nanometer materials.Graphene oxide (GO) is the derivant of grapheme treated by oxidationtreatment, which sizes distribute from ten nm, hundreds of nanometer tomicron; due to its higher efficiency of fluorescence quenching, goodstability of aqueous solution, larger specific surface area, as well as a lot ofhydroxyl, carbonyl and carboxyl epoxy randomly distribute over its surface,which mainly containing unique properties of oxygen functional groups, ithas a great biological outlook. With more and more related researchincreasing, GO shows a inestimable application prospect. Some studies[1]have shown that nanometer materials could diffuseinto all tissues when it got into the body, then shuttled back and forthamong all the parts of the body except the brain like small molecules, andthat is quite distinct from common materials. But other studies indicatedthat nanometer materials displayed a certain cytotoxicity, which couldinduce cell apoptosis and change the expression of genes[2-5]. Regarding forthese reasons, some magazines like Science and Nature published series ofarticles aimed directly at the biosafety of nanometer materials and theproblems of the development, so then remind to notice the negativeeffect[6-8]. However, so far there are only few potential toxicity studies ofGO in vivo, and especially lack systematic and comprehensive toxicologyresearch. Nowadays, the potential toxicity study of GO is very few in vivo,and lack of systematic and comprehensive toxicology research, especially.Therefore, it is important and urgency to study the potential toxicity of GOin biology. Herein, this research will evaluate the biological safety of GOand to observe the sub-acute toxicological effects of GO in male SD rats bythe method of tail vein injection with different concentrations of GO for7d,and provide scientific data for the clinic and application of many fields.Method:1.Characterization and identification of GOObservation of the surface characteristics, absorption band and surface groups by HRTEM, UV and Raman spectrum, respectively.2. Animal experiment32cleaning SD rats weighing90-95g (Male,4-5weeks old) wereassigned to four dosage groups randomly with8rats per group: Thecontrol group: GO0mg/kg b.w.; Low dose group: GO2.5mg/kg b.w.;The middle dose group: GO5mg/kg b.w.;â‘£High dose group: GO10mg/kg b.w.. Then, GO was injected to rats by tail vein once a day, allanimals were sacrificed after consecutive injection for7d. The programswere observed and recorded during the experiment as followings:2.1General condition: Activities, mental state, individual body weightand feed consumption of rats were measured and recorded daily during theexperiment period.2.2Neurobehavioral experiments: OFT and FOB test were observed tocomprehensive evaluate the neural active movement, activity of the centralnervous system, central nervous system stimulation, neuromuscularresponse, sensorimotor function of experimental animals on the first dayand the seventh day of injection, respectively.2.3On the seventh day, blood samples were collected forhematological (blood routine, blood coagulation) and biochemical analysisbefore all animals were sacrificed.2.4Organs (brain, heart, liver, spleen, lung, kidney, thymus, adrenalgland, prostate, testis, epididymis) were harvested for weighing and calculation of the organ coefficient.2.5The main tissues (brain, heart, liver, spleen, lung, kidney, lymphgland) were collected for histopathological observation after formalin fixed,paraffin-embedded, sliced and HE stained.Result:1. All animals were generally in good condition without the occurrenceof death and disease. Meanwhile, there was no significant differences in thedaily food consumption and body weight (compared with the control group,P>0.05).2. The neuroethology of general activities and nerve muscle testing,sensorimotor and excitatory test, autonomous activity of OFT, FOB testgroups were not show significantly differences (P>0.05).3. The results of the blood biochemical examination showed CHO,HDL, LDL levels of the high dose group were significantly reduced (bothcompared with the control group and low dose group, P<0.05). Otherblood/serum biochemical parameters were not show significantlydifferences(compared with the control group, P>0.05).4. All organ coefficients were have no changes (compared with thecontrol group, P>0.05).5. At the concentration of GO10mg/kg b.w.(compared with the controlgroup), it can be seen pulmonary capillary congestion, alveolar wall thickening and alveolar cavity decreased in the lung tissue, and with fewGO particles scattered. Local vascular congestion and phagocytic functionactive can be seen in the lung, liver and spleen(GO particles can not beseen). Brain, heart, kidney, lymph nodes had no obvious change. Whilebellow the concentration of GO5mg/kg b.w., these organs have not showobvious histopathological changes.Conclusion:1. No obvious toxicity was showed on the growth and development,mental state and behavior of male SD rats, with the possible reason is thatGO cannot pass though the blood brain/blood cerebrospinal barrier.2. There were no significant effect on blood routine, blood glucose,liver and kidney function. But at the concentration of GO10mg/kg b.w., itcan reduce the CHO, HDL and LDL levels in the blood, so it may have acertain role in reducing blood lipids.3. At the concentration of GO10mg/kg b.w., no obvious toxicity onthe brain, heart, kidney and lymph gland, but it can accumulated in the lung,liver. And cause hyperplasia, phagocytic, vascular congestion in the lung,liver ang spleen. When the concentration is below5mg/kg b.w., there wereno obvious pathological injury and accumulation of GO in the lung, liver,spleen.In a word, GO has good biological safety at the dose of2.5-10mg/kg b.w. and the time of7d in this experiment. |
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