RESUMO
Although the kidneys comprise a critical target of uranium exposure, the dynamics of renal uranium distribution have remained obscure. Uranium is considered to function physiologically in the form of uranyl ions that have high affinity for phosphate groups. The present study applied microbeam-based elemental analysis to precisely determine the distribution of phosphorus and uranium in the kidneys of male Wistar rats exposed to uranium. One day after a single subcutaneous injection of uranyl acetate (2 mg/kg), areas of concentrated phosphorus were scattered in the S3 segments of the proximal tubule of the kidneys, whereas the S3 segments in control rats and in rats given a lower dose of uranium (0.5 mg/kg) contained phosphorus without concentrated phosphorus. Areas with concentrated phosphorus contained uranium 4- to 14-fold more than the mean uranium concentration (126-472 vs. 33.1 ± 4.6 µg/g). The chemical form of uranium in the concentrated phosphorus examined by XAFS was uranium (VI), suggesting that the interaction of uranyl ions with the phosphate groups of biomolecules could be involved in the formation of uranium concentration in the proximal tubules of kidneys in rats exposed to uranium.
Assuntos
Túbulos Renais Proximais/metabolismo , Compostos Organometálicos , Fósforo/metabolismo , Urânio/metabolismo , Animais , Túbulos Renais Proximais/patologia , Masculino , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/farmacologia , Ratos , Ratos WistarRESUMO
The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U LIII-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175â keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.
Assuntos
Rim , Urânio , Animais , Rim/efeitos dos fármacos , Túbulos Renais Proximais , Ratos , Urânio/toxicidadeRESUMO
For understanding trace element dynamics in tissues, methods for analyzing elemental distribution and localization without destroying tissue structures and cell arrangements are desired. Synchrotron radiation X-ray fluorescence (SR-XRF) analysis is one of the non-destructive and multi-element simultaneous analyses. The kidney is the major excretion pathway of cesium (Cs) taken into the body, and an understanding of cesium distribution in the kidney would be useful for establishing technology to facilitate the excretion of radioactive Cs from the body due to nuclear disasters. In the present study, the distribution of cesium and trace elements, such as iron (Fe) and zinc (Zn), corresponding to the kidney structure was examined in Cs-administered mice by SR-XRF imaging with high-energy excitation X-rays (40 keV). By beam scanning with a 200-µm square beam, clear Cs images corresponding to the renal layer structure were obtained for the renal specimen at the early phase after Cs administration with the mean renal Cs concentration of 24.1 ± 3.2 µg/g. Cs was distributed mainly in the medulla and the outer stripe of the outer medulla located in the center area of the kidney. Unlike the Cs distribution, endogenous Fe and Zn tended to be lower in the medulla than in the outer stripe of the outer medulla and the cortex. This method is effective for analyzing Cs distribution because it can simultaneously analyze the distribution of endogenous trace elements.
RESUMO
Spinel-type inorganic pigments with intensive color and chemical/thermal stability are showing extensive applications that could be further broadened by color manipulation and improvement of the material properties through nanosizing. In this study, we report the supercritical hydrothermal synthesis of nonstoichiometric spinel-type cobalt gallate nanoparticles (Co-Ga NPs) with controlled color. Without the conventional calcination procedure, NPs with greenish-blue, blue, and yellowish-green colors were synthesized from precursor solutions at pH 7, 9, and 11, respectively, with a low Co/Ga molar ratio of 0.25. X-ray diffraction, scanning/transmission electron microscopy, and inductively coupled plasma-atomic emission spectroscopy methods suggest that the products were spinel-type cobalt gallate NPs with high crystallinity and a nonstoichiometric composition. Based on an X-ray absorption fine structure investigation, the prepared nonstoichiometric Co-Ga NPs were found to have different cationic configurations from stoichiometric CoGa2O4 produced by a solid-state reaction during calcination. Meanwhile, the degrees of distortions at tetrahedral and octahedral sites in the NPs were evaluated by Raman spectroscopy. In particular, nonstoichiometric Co-Ga NPs with a blue color were prepared without calcination for the first time and were found to have lower tetrahedral cobalt occupancy but comparable octahedral cobalt occupancy and larger polyhedral distortions at tetrahedral sites when compared to calcined CoGa2O4. We also discuss strategies that could realize Co-Ga NPs with a more brilliant blue color using the present technique based on an investigation of the growth process.
RESUMO
Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiOx NPs) are promising radiosensitizers that enhance the therapeutic effect of X-ray irradiation after local injection into tumors. However, the mechanism for this reaction has remained unclear with the exception of the involvement of hydrogen peroxide (H2O2), which is released by PAA-TiOx NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiOx NPs with free H2O2 molecules to investigate the effect exerted on the radiosensitivity of cancer cells in vitro. A cell-free dialysis method revealed that a portion of the H2O2 adsorbed onto the PAA-TiOx NPs during synthesis could be released during a treatment regimen. The H2O2 release lasted for 7 h, which was sufficient for one radiation treatment procedure. For in vitro experiments, cultured human pancreatic cancer cells took up PAA-TiOx NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiOx NP or H2O2 solution, the intracellular H2O2 levels remained higher with PAA-TiOx NP treatment compared with the H2O2 solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular H2O2 levels. These results indicate that PAA-TiOx NPs are efficient carriers of H2O2 into cancer cells and thus enhance the radiosensitivity.
Assuntos
Nanopartículas , Neoplasias , Radiossensibilizantes , Humanos , Peróxido de Hidrogênio , TitânioRESUMO
The structural change on the molecular scale of anatase-type TiO(2) during hydrothermal treatment was investigated in detail by various analytic techniques such as X-ray absorption fine structure and transmission electron microscopy in order to clarify the formation mechanisms of titanate-based nanotubes. It revealed that the nanosheet-like products composed of highly distorted TiO(6) octahedra were generated by hydrothermal treatment of anatase-type TiO(2), and then the anatase-like structures are partially built up with the formative nanotubes by scrolling up these nanosheet-like products and nanosheets.
RESUMO
Polyacrylic acid (PAA)-modified titanium peroxide nanoparticles (PAA-TiOx NPs) are promising radiosensitizers. PAA-TiOx NPs were synthesized from commercial TiO2 nanoparticles that were modified with PAA and functionalized by H2O2 treatment. To realize practical clinical uses for PAA-TiOx NPs, their tissue distribution and acute toxicity were evaluated using healthy mice and mice bearing tumors derived from xenografted MIAPaCa-2 human pancreatic cancer cells. Healthy mice were injected with PAA-TiOx NPs at 25 mg/kg body weight via the tail vein, and tumor-bearing mice were injected either into the tumor locally or via the tail vein. The concentration of PAA-TiOx NPs in major organs was determined over time using inductively coupled-plasma atomic emission spectrometry. After 1 h, 12% of the PAA-TiOx NP dose had accumulated in the tumor, and 2.8% of the dose remained after 1 week. Such high accumulation could be associated with enhanced permeability and retention effects of the tumor, as PAA-TiOx NPs are composed of inorganic particles and polymers, without tumor-targeting molecules. The liver accumulated the largest proportion of the injected nanoparticles, up to 42% in tumor-bearing mice. Blood biochemical parameters were also investigated after intravenous injection of PAA-TiOx NPs in healthy mice. PAA-TiOx NPs invoked a slight change in various liver-related biochemical parameters, but no liver injury was observed over the practical dose range. In the future, PAA-TiOx NPs should be modified to prevent accumulation in the liver and minimize risk to patients.
Assuntos
Resinas Acrílicas/química , Nanopartículas , Radiossensibilizantes/efeitos adversos , Radiossensibilizantes/síntese química , Radiossensibilizantes/farmacocinética , Titânio/química , Resinas Acrílicas/efeitos adversos , Resinas Acrílicas/farmacocinética , Animais , Linhagem Celular Tumoral , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/efeitos adversos , Nanopartículas/química , Nanopartículas/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/radioterapia , Peróxidos/efeitos adversos , Peróxidos/síntese química , Peróxidos/química , Peróxidos/farmacocinética , Polímeros/metabolismo , Radiossensibilizantes/química , Distribuição Tecidual , Titânio/efeitos adversos , Titânio/farmacocinética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
An induction of polyacrylic acid-modified titanium dioxide with hydrogen peroxide nanoparticles (PAA-TiO2/H2O2 NPs) to a tumor exerted a therapeutic enhancement of X-ray irradiation in our previous study. To understand the mechanism of the radiosensitizing effect of PAA-TiO2/H2O2 NPs, analytical observations that included DLS, FE-SEM, FT-IR, XAFS, and Raman spectrometry were performed. In addition, highly reactive oxygen species (hROS) which PAA-TiO2/H2O2 NPs produced with X-ray irradiation were quantified by using a chemiluminescence method and a EPR spin-trapping method. We found that PAA-TiO2/H2O2 NPs have almost the same characteristics as PAA-TiO2. Surprisingly, there were no significant differences in hROS generation. However, the existence of H2O2 was confirmed in PAA-TiO2/H2O2 NPs, because spontaneous hROS production was observed w/o X-ray irradiation. In addition, PAA-TiO2/H2O2 NPs had a curious characteristic whereby they absorbed H2O2 molecules and released them gradually into a liquid phase. Based on these results, the H2O2 was continuously released from PAA-TiO2/H2O2 NPs, and then released H2O2 assumed to be functioned indirectly as a radiosensitizing factor.
Assuntos
Resinas Acrílicas/química , Peróxido de Hidrogênio/química , Nanopartículas/química , Radiossensibilizantes/química , Titânio/química , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Biological applications of nanoparticles are rapidly increasing, which introduces new possibilities to improve the efficacy of radiotherapy. Here, we synthesized titanium peroxide nanoparticles (TiOxNPs) and investigated their efficacy as novel agents that can potently enhance the effects of radiation in the treatment of pancreatic cancer. METHODS: TiOxNPs and polyacrylic acid-modified TiOxNPs (PAA-TiOxNPs) were synthesized from anatase-type titanium dioxide nanoparticles (TiO2NPs). The size and morphology of the PAA-TiOxNPs was evaluated using transmission electron microscopy and dynamic light scattering. The crystalline structures of the TiO2NPs and PAA-TiOxNPs with and without X-ray irradiation were analyzed using X-ray absorption. The ability of TiOxNPs and PAA-TiOxNPs to produce reactive oxygen species in response to X-ray irradiation was evaluated in a cell-free system and confirmed by flow cytometric analysis in vitro. DNA damage after X-ray exposure with or without PAA-TiOxNPs was assessed by immunohistochemical analysis of γ-H2AX foci formation in vitro and in vivo. Cytotoxicity was evaluated by a colony forming assay in vitro. Xenografts were prepared using human pancreatic cancer MIAPaCa-2 cells and used to evaluate the inhibition of tumor growth caused by X-ray exposure, PAA-TiOxNPs, and the combination of the two. RESULTS: The core structures of the PAA-TiOxNPs were found to be of the anatase type. The TiOxNPs and PAA-TiOxNPs showed a distinct ability to produce hydroxyl radicals in response to X-ray irradiation in a dose- and concentration-dependent manner, whereas the TiO2NPs did not. At the highest concentration of TiOxNPs, the amount of hydroxyl radicals increased by >8.5-fold following treatment with 30 Gy of radiation. The absorption of PAA-TiOxNPs enhanced DNA damage and resulted in higher cytotoxicity in response to X-ray irradiation in vitro. The combination of the PAA-TiOxNPs and X-ray irradiation induced significantly stronger tumor growth inhibition compared to treatment with either PAA-TiOxNPs or X-ray alone (p < 0.05). No apparent toxicity or weight loss was observed for 43 days after irradiation. CONCLUSIONS: TiOxNPs are potential agents for enhancing the effects of radiation on pancreatic cancer and act via hydroxyl radical production; owing to this ability, they can be used for pancreatic cancer therapy in the future.
Assuntos
Neoplasias Pancreáticas/patologia , Radiossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Titânio/farmacologia , Absorciometria de Fóton , Animais , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Humanos , Masculino , Nanopartículas Metálicas , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Espécies Reativas de Oxigênio/efeitos da radiação , Raios X , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Oral lichen planus (OLP) and oral lichenoid contact lesions (OLCL) are chronic inflammatory mucocutaneous reactions with a risk of malignant transformation that alter the epithelium. OLP and OLCL have similar clinical and histopathological features and it is difficult to distinguish one from the other. Metallic restorations are suspected to generate OLCLs. Trace metal analysis of OLCL specimens may facilitate the discrimination of symptoms and identification of causative metallic restorations. The purpose of this study was to assess OLCL tissue samples for the prevalence of metallic elements derived from dental restorations, and to discriminate OLCL from OLP by using synchrotron radiation-excited X-ray fluorescence analysis (SR-XRF), particle-induced X-ray emission (PIXE), and X-ray absorption fine structure (XAFS). Typical elements of dental materials were detected in the OLCL, whereas no obvious element accumulation was detected in OLP and negative control specimens. The origin of the detected metallic elements was presumed to be dental alloys through erosion. Therefore, our findings support the feasibility of providing supporting information to distinguish OLCL from OLP by using elemental analysis.
Assuntos
Líquen Plano Bucal/metabolismo , Mucosa Bucal/metabolismo , Oligoelementos/metabolismo , Adulto , Ligas Dentárias/efeitos adversos , Feminino , Humanos , Líquen Plano Bucal/induzido quimicamente , Líquen Plano Bucal/patologia , Masculino , Mucosa Bucal/patologiaRESUMO
The mass production of highly dense oxides with high-temperature and high-pressure phases allows us to discover functional properties that have never been developed. To date, the quenching of highly dense materials at the gramme-level at ambient atmosphere has never been achieved. Here, we provide evidence of the formation of orthorhombic Fe2TiO4 from trigonal FeTiO3 as a result of the high-temperature (>1250 K) and high-pressure (>23â GPa) condition induced by the high collision energy of 150 gravity generated between steel balls. Ilmenite was steeply quenched by the surrounding atmosphere, when iron-rich ilmenite (Fe2TiO4) with a high-temperature and high-pressure phase was formed by planetary collisions and was released from the collision points between the balls. Our finding allows us to infer that such intense planetary collisions induced by high-energy ball milling contribute to the mass production of a high-temperature and high-pressure phase.
RESUMO
In this study, the effect of post acid treatments with HCl aqueous solutions after the hydrothermal process on the microstructure of TiO2-derived titanate nanotube was investigated. Especially, the relationship between local structural changes with the HCl treatment and their thermal stability were investigated by X-ray absorption fine structure (XAFS). Consequently, it revealed that the replacement of Na+ with H+ (proton exchange) in TiO2-derived titanate nanotubes was caused by the acid treatment with HCl aqueous solutions and the excess acid treatment led to the disordering. Moreover, it was confirmed that the minor change of TiOx polyhedra in TiO2-derived titanate nanotubes was also related with this disordering.