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Mori T Ito S Namiki M Suzuki T Kobayashi S Matsubayashi K Sawaguchi T 《Toxicology》2007,236(3):149-157
An increase in polydrug abuse is a major problem worldwide. The coadministration of methamphetamine and morphine increased subacute toxicity or lethality in rodents. However, the underlying mechanisms by which lethality is increased by the coadministration of methamphetamine and morphine are not yet fully understood. Coadministered methamphetamine and morphine induced lethality by more than 80% in BALB/c mice, accompanied by the rupture of cells in the kidney and liver, and an increase in poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine was significantly attenuated by pretreatment with mepacrine (phospholipase A(2) inhibitor) or fullerene (a radical scavenger), or by cooling from 30 to 90 min after drug administration. Furthermore, based on the results of the electron spin resonance spin-trapping technique, hydroxyl radicals were increased by the administration of methamphetamine and morphine, and these increased hydroxyl radicals were potently attenuated by fullerene and cooling. These results suggest that hydroxyl radicals plays an important role in the increased lethality induced by the coadministration of methamphetamine plus morphine. The potency of cooling or drugs for decreasing the subacute toxicity or lethality induced by the coadministration of methamphetamine and morphine was in the order fullerene=cooling>mepacrine. These results indicate that fullerene and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine. 相似文献
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Elsa Maria Matern Ademar Wong Tayane Aguiar Freitas Ronaldo Censi Faria Osvaldo N. Oliveira Jr. 《Journal of Pharmaceutical Analysis》2021,11(5):646
Monitoring the concentration of antibiotics in body fluids is essential to optimizing the therapy and minimizing the risk of bacteria resistance, which can be made with electrochemical sensors tailored with appropriate materials. In this paper, we report on sensors made with screen-printed electrodes (SPE) coated with fullerene (C60), reduced graphene oxide (rGO) and Nafion (NF) (C60-rGO-NF/SPE) to determine the antibiotic metronidazole (MTZ). Under optimized conditions, the C60-rGO-NF/SPE sensor exhibited a linear response in square wave voltammetry for MTZ concentrations from 2.5 × 10−7 to 34 × 10−6 mol/L, with a detection limit of 2.1 × 10−7 mol/L. This sensor was also capable of detecting MTZ in serum and urine, with recovery between 94% and 100%, which are similar to those of the standard chromatographic method (HPLC-UV). Because the C60-rGO-NF/SPE sensor is amenable to mass production and allows for MTZ determination with simple principles of detection, it fulfills the requirements of therapeutic drug monitoring programs. 相似文献
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Fullerene derivatives: an attractive tool for biological applications 总被引:24,自引:0,他引:24
The fullerene family, and especially C60, has very appealing photo-, electro-chemical and physical properties, which can be exploited in many and different biological fields. Fullerene is able to fit inside the hydrophobic cavity of HIV proteases, inhibiting the access of substrates to the catalytic site of the enzyme. It can be used as radical scavenger; in fact some water-soluble derivatives are able to reduce ROS concentrations. At the same time, if exposed to light, fullerene can produce singlet oxygen in high quantum yields. This action, together with the direct electron transfer from excited state of fullerene and DNA bases, can be used to cleave DNA. In this review we report the most recent aspects of fullerene biological applications. 相似文献
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富勒烯及其衍生物是一类具有独特物理化学特性的化合物,在生物医学领域有广泛的应用前景。介绍该类化合物的合成及制备,富勒烯笼外配合物的抗HIV病毒、断裂DNA和清除自由基等生物学活性,以及富勒烯金属包合物在核医学诊断中的应用研究。 相似文献
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《Toxicology in vitro》2014,28(8):1474-1481
Immunotoxicity studies of nanoparticles on T cells addressed their effects on activation by T antigen receptor, but have neglected the regulation of proliferation by IL-2. In this study, the IL-2-dependent T lymphoblastoid WE17/10 cell line was used to compare silver (Ag-NPs) and fullerene (C60-NPs) nanoparticles’ toxicity and evaluate whether these NPs could interfere with IL-2-dependent proliferation. Results have shown that Ag-NPs are more toxic, as they reduced cell viability at the highest concentration tested (100 μg/ml), while C60-NPs have shown good biocompatibility. Characterization of NP suspensions by dynamic light scattering measured large aggregates for C60-NPs, whereas Ag-NPs were relatively stable and well dispersed. This translated into a much larger uptake of Ag-NPs compared to C60-NPs, as measured by flow cytometry. Proliferation measurements by CFSE following 72 h incubation have shown that Ag-NPs decrease cell proliferation and C60-NPs slightly increase proliferation. CD25 expression was unchanged following exposure to C60-NPs, but was significantly increased by Ag-NPs’ presence for short and long-term incubations. Analyses of three key signaling proteins activated by IL-2 receptor (Stat5, JNK and ERK1/2) by western immunoblotting have shown no effects from either NPs on Stat5 and JNK phosphorylation. ERK1/2 was slightly activated following a short exposure to Ag-NPs, while C60-NPs had no effect. Our results show that C60-NPs have good biocompatibility and do not interfere with IL-2-dependent proliferation. A deeper investigation would be needed for the case of Ag-NPs, since the mechanism of their action is still unclear. 相似文献
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《Toxicology in vitro》2015,29(8):1474-1481
Immunotoxicity studies of nanoparticles on T cells addressed their effects on activation by T antigen receptor, but have neglected the regulation of proliferation by IL-2. In this study, the IL-2-dependent T lymphoblastoid WE17/10 cell line was used to compare silver (Ag-NPs) and fullerene (C60-NPs) nanoparticles’ toxicity and evaluate whether these NPs could interfere with IL-2-dependent proliferation. Results have shown that Ag-NPs are more toxic, as they reduced cell viability at the highest concentration tested (100 μg/ml), while C60-NPs have shown good biocompatibility. Characterization of NP suspensions by dynamic light scattering measured large aggregates for C60-NPs, whereas Ag-NPs were relatively stable and well dispersed. This translated into a much larger uptake of Ag-NPs compared to C60-NPs, as measured by flow cytometry. Proliferation measurements by CFSE following 72 h incubation have shown that Ag-NPs decrease cell proliferation and C60-NPs slightly increase proliferation. CD25 expression was unchanged following exposure to C60-NPs, but was significantly increased by Ag-NPs’ presence for short and long-term incubations. Analyses of three key signaling proteins activated by IL-2 receptor (Stat5, JNK and ERK1/2) by western immunoblotting have shown no effects from either NPs on Stat5 and JNK phosphorylation. ERK1/2 was slightly activated following a short exposure to Ag-NPs, while C60-NPs had no effect. Our results show that C60-NPs have good biocompatibility and do not interfere with IL-2-dependent proliferation. A deeper investigation would be needed for the case of Ag-NPs, since the mechanism of their action is still unclear. 相似文献
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Colloidal fullerene nanoparticles (nC60) were reported to be toxic to fish brains, human cells and microorganisms, while new observations suggest that the observed toxicity may be due to tetrahydrofuran (THF) solvent or its oxidative by-products in nC60 preparations. Here, we report a novel method for preparing nC60 nanoparticles that does not use THF solvent, but provides nC60 with an average particle size of 43.8 nm and a yield approximately 100 times higher than the THF method. The prepared nC60 showed a similar antioxidant capacity compared to a water-soluble vitamin E analog. No mortality to human epidermal keratinocytes was observed at a concentration 170 times higher than the reported LC50 values for other human cell lines. No toxicity was observed to E. coli or B. subtilis at up to 342 μg/mL nC60 for 16 h, which was hundred times higher than the reported minimum inhibitory concentrations of nC60 prepared using THF method for these two bacteria. When E. coli was exposed to 85.5 μg/mL nC60 with daily passage for 4 days, the stationary phase populations at different passages were not statistically different (p = 0.05) from the control without nC60 nanoparticles. These results reveal that the intrinsic biological property of nC60 is non-toxic, confirming the prior non-toxic reports when using nC60 prepared with non-THF methods. 相似文献
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Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes 总被引:2,自引:0,他引:2
Jillian G. Rouse Jianzhong Yang Andrew R. Barron Nancy A. Monteiro-Riviere 《Toxicology in vitro》2006,20(8):1313-1320
The functionalization of C60 with such complexes as amino acids has the potential to provide greater interaction between the fullerene and the biological environment yielding potential new medical and pharmacological applications. Although scientific research in the past decade has revealed much about the chemical and physical properties of C60, the biological activities of this compound and its derivatives are still relatively unclear. In an attempt to understand the biological activity of functionalized C60, human epidermal keratinocytes (HEK) were exposed to fullerene-based amino acid (Baa) solutions ranging in concentrations of 0.4–0.00004 mg/mL in a humidified 5% CO2 atmosphere at 37 °C. MTT cell viability after 48 h significantly decreased (p < 0.05) for concentrations of 0.4 and 0.04 mg/mL. In an additional study, human cytokines IL-6, IL-8, TNF-, IL-1β, and IL-10 were assessed for concentrations ranging from 0.4–0.004 mg/mL. Media was harvested at 1, 4, 8, 12, 24 and 48 h for cytokine analysis. IL-8 concentrations for the 0.04 mg/mL treatment were significantly greater (p < 0.05) than all other concentrations at 8, 12, 24, and 48 h. IL-6 and IL-1β activities were greater at the 24 h and 48 h for 0.4 and 0.04 mg/mL. No significant TNF- or IL-10 activity existed at any time points for any of the concentrations. These results indicate that concentrations lower than 0.04 mg/mL initiate less cytokine activity and maintain cell viability. In HEK, Baa concentrations of 0.4 and 0.04 mg/mL decrease cell viability and initiate a pro-inflammatory response. 相似文献