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OBJECTIVE: To study the effect of nano-cerium oxide on the early development of zebrafish embryos. METHODS: The well-developed zebrafish embryos were randomly divided into the control group and the 50, 100, 200, 400 and 800 mg/L dose groups, with 40 embryos in each group. The dose groups were treated with nano-cerium oxide at the corresponding mass concentration for 5 days. The control group received no treatment. The death and malformation of embryos were observed. The heart rate of zebrafish embryos was recorded using confocol microscope. The protein expression of microtubule-associated protein 1 light chain 3(LC3) and cleaved Caspase-3 and were observed by Western blot technology. RESULTS: The death and embryonic malformation rate of zebrafish embryos increased with the increase of doses, showing statistical significance(P<0.01). The heart rate of the 800 mg/L dose group was decreased compared with the control group [(77±8) vs(93±4) beats/min, P<0.01]. There was no statistical significant difference in LC3-Ⅱ protein expression in each groups(P>0.05). The cleaved Caspase-3 protein expression increased in all dose groups compared with the control group(P<0.05). The cleaved Caspase-3 protein expression in the 200 mg/L dose group was higher than that in the 50 mg/L dose group(P<0.05). CONCLUSION: The nano-cerium oxide may induce cell apoptosis, causing toxic effect in early development of zebrafish embryos.
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Objective To investigate the effects of cerium oxide nanoparticles of different sizes on the number and constructions of immune cells in peripheral blood of mice after X-ray irradiation. Methods Mice were randomly divided into 4 groups according to body weight layer and the weight of each mouse was weighed. All mice were divided into 6 groups according to weight from high to low, and there were 4 mice in each group. Then 1 mouse was randomly taken from each group to form the control group. Model group, 5 nm and 25 nm cerium oxide nanoparticles groups were formed in turn. There were 6 mice in each group. The mice in model group and cerium oxide nanoparticles administration groups were irradiated once with 3 Gy of X-rays. The mice in cerium oxide nanoparticles groups began to be intraperitoneally administrated once a day with 10 μg 5 nm or 25 nm cerium oxide nanoparticles per kilogram body weight on the 4th day before irradiation and once every other 2 days after irradiation. The mice in the control group and model group were intraperitoneally administrated with 0.9 % saline. The mice were killed on the 10th days after irradiation. White cells count (WBC) and classification in peripheral blood were detected by using automatic globulimeter, and lymphocyte subsets were analyzed by using flow cytometry. Results Compared with the control group, the number of WBC, neutrophil granulocytes, monocytes, lymphocytes, total T lymphocytes, CD4+and CD8+T lymphocytes and the percentages in the model group were decreased (all P＜0.05), and percentages of the lymphocytes, B cells and NK cells and ratio of CD4 to CD8 were increased in model group (all P＜ 0.05). Compared with the model group, the above parameters except percentages of T lymphocytes, CD4+and CD8+T lymphocytes were improved in mice of 5 nm cerium oxide nanoparticle group (all P ＜0.05). Compared with the control group, the number of WBC and lymphocytes were decreased in the 5 nm cerium oxide nanoparticle group (P＜0.05), and there were no significances in other parameters compared with the control group (all P ＞0.05). Compared with the control group, the number of WBC and lymphocytes, the number and percentages of T lymphocytes, CD4+and CD8+T lymphocytes and the percentages were decreased (all P＜ 0.05), and percentage of NK cells and ratio of CD4 to CD8 were significantly increased in 25 nm cerium oxide nanoparticles group (all P＜ 0.05). The number of lymphocytes and CD8+T lymphocytes in 25 nm cerium oxide nanoparticles group was lower than that in 5 nm cerium oxide nanoparticles group (all P ＜ 0.05). Conclusions The effects of cerium oxide nanoparticles of different sizes on the immune cells of mice after X-ray irradiation are different, and 5 nm cerium oxide nanoparticle is superior to 25 nm cerium oxide nanoparticle.
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OBJECTIVE: To observe the in vivo metabolism and distribution characteristics of nano-cerium oxide( nanoCeO_2) in rats,and to explore the radio-protective effect of nano-CeO_2. METHODS: i) A total of 18 specific pathogen free( SPF) SD rats were randomly divided into 3 groups. Rats of experiment group and CeO_2 blood group were gavaged with1. 0 g/kg body weight( bw) nano-CeO_2 suspension. Rats of control group were gavaged with double distilled water( DDW)in equal volume. At different time-points after treatment,venous blood was collected from the rats' eye socket in CeO_2 blood group,meanwhile urine and excrement of rats of experiment group were also collected. Organ and tissue samples of experiment group and control group were collected 24. 0 hours after treatment. The concentrations of cerium in biological samples were detected by inductively coupled plasma mass spectrometry. ii) A total of 72 SPF BALB/c mice were randomly divided into 6 groups. Mice of low-,medium-and high-dose groups were gavaged with 100,300 and 900 mg/kg bw nano-CeO_2 suspension respectively. Mice of negative control group,irradiation control group and drug positive control group were gavaged with DDW in equal volume once daily. After 14 days,mice of the other 5 groups were exposed by60Coγ-rays once with 3. 5 Gy( 1 Gy/min) except the negative control group. Mice of drug positive control group were given intraperitoneal injection with 200 mg/kg bw amifostine half an hour before irradiation. After exposure,mice were treated by the above gavages once daily. After 3 and 8 days,6 mice were randomly selected to collect the peripheral blood for the count of white blood cell( WBC) and lymph cell measuring. RESULTS: i) The cerium concentration in blood reached peak value in 4. 0 hours after exposure of nano-CeO_2,and the cerium concentration of urine and excrement reached maximum in8. 0 hours after exposure. After 24. 0 hours of exposure,the cerium concentration of brain in experiment group was higher than that of control group( P < 0. 05). Among the experiment group,the cerium concentrations of sternum,duodenum and brain were higher than that of kidney and heart( P < 0. 05),meanwhile the cerium concentrations of thymus and lung were higher than that of kidney( P < 0. 05). ii) There was no statistical difference in interactive effect of WBC count and lymph cell counts between nano-CeO_2 exposure ways and time( P > 0. 05). The WBC counts of the low-and medium-dose groups were lower than those of the negative control group and the drug positive control group( P < 0. 05). The WBC count of high-dose group was lower than those of irradiation control group,drug positive control group and medium-dose group( P <0. 05). The lymph cell counts of the 3 dose groups were lower than that of drug positive control group( P < 0. 05).CONCLUSION: The nano-CeO_2 is mainly cumulated in organs such as sternum,duodenum,brain,thymus and lung. After induced by radiation,nano-CeO_2 has a certain degree of promotion role in increasing the WBC counts.
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Objective To study the impact of different low concentrations of cerium oxide for hepatocellular carcinoma cell prolifera-tion.Methods Three different types of hepatoma cells (Huh7, HepG2,7721) were cultured,and added different concentrations of cerium oxide (0.005,0.01,0.05,0.1,1 μg/mL),of which the cell proliferation was detected by CCK8.The apoptosis-related genes was detected by qRT-PCR technology.The cell cycle was analyzed by flow cytometry.And the effect of low concentration cerium oxide on hepatocellular carci-noma cells tumorigenicity was confirmed by the nude mice experiments.Results CCK8 experiment showed that low concentrations of cerium oxide could promote proliferation of hepatocellular carcinoma cell, especially in concentration of 0.01μg/mL.The qRT-PCR showed that low concentration of cerium oxide could inhibit the apoptosis of hepatocellular carcinoma cell.The flow cytometry analysis had not found any effect of cerium oxide on cell cycle.The tumorigenicity experiments confirmed that low concentrations of cerium oxide could enhance the tumorigenic ability of hepatocellular carcinoma cell.Conclusion Low concentration of cerium oxide can significantly improve the proliferation of liver cancer cells.
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During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles (nanoceria), considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke (CIS), cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.
Subject(s)
Humans , Antioxidants , Therapeutic Uses , Brain Ischemia , Drug Therapy , Cerium , Chemistry , Therapeutic Uses , Nanoparticles , Chemistry , Therapeutic Uses , Neuroprotective Agents , Therapeutic Uses , Oxidative Stress , Reactive Nitrogen Species , Metabolism , Reactive Oxygen Species , Stroke , Drug Therapy , PathologyABSTRACT
OBJECTIVES: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs. METHODS: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis. RESULTS: No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05). CONCLUSIONS: Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.