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ABSTRACT: Abstract The application of carbon nanotube (CNT) as a functional material to engineering and life sciences is advanced. In order to evaluate the cytotoxicity of CNT in vitro, some chemical and biological reagents are used for dispersants. In the present study, the cellular influences of six kinds of chemical or biological reagents used as dispersants were examined. Pluronic F-127, Pluronic F-68, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), pulmonary surfactant preparation Surfacten®, bovine serum albumin (BSA) and Tween 80 were used in the preparation of CNT-medium dispersants. The influences of each reagent on cell viability in human lung carcinoma A549 cells were small. However, Pluronic F-127, DPPC, Surfacten® and Tween 80 induced an increase of intracellular reactive oxygen species (ROS) level. Next, CNT-medium dispersions were prepared, using each reagent as a dispersant and applied to A549 cells. The cellular influences depended on the kind of dispersant. Cells exposed to CNT dispersion including Pluronic® F-127, Surfacten®, DPPC and Tween 80 showed LDH release to the culture supernatant. Induction of intracellular ROS level was observed in cells exposed to CNT dispersion including each reagent except BSA. These results suggest that the adsorbed dispersant reagents on the surface of the CNT affect its cellular influences, particularly the induction of oxidative stress.
Toxicology mechanisms and methods 01/2013; · 1.03 Impact Factor
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Yohei Mizuguchi,
Toshihiko Myojo,
Takako Oyabu,
Masayoshi Hashiba,
Byeong Woo Lee,
Makoto Yamamoto,
Motoi Todoroki,
Kenichiro Nishi,
Chikara Kadoya,
Akira Ogami, Yasuo Morimoto,
Isamu Tanaka,
Manabu Shimada,
Kunio Uchida,
Shigehisa Endoh,
Junko Nakanishi
[show abstract]
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ABSTRACT: Inhalation studies and intratracheal instillation studies using laboratory animals are commonly conducted for pulmonary toxicity tests of nanomaterials. In our study, male Wister rats were exposed to nickel oxide (NiO) particles including a nano-scale, even for aerosols and suspensions, in a 4-week inhalation and intratracheal instillation. Using polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid as a biomarker of inflammation, we attempted to quantify the relationship between responses to inhalation and intratracheal instillation of the nanoparticles, based on surface area doses. Four kinds of NiO suspension samples with different specific surface areas were singly injected via the tracheas of the rats. The relationship between the instilled doses and PMN production was examined 3 days and 1 month after the instillation. In parallel, 4-week inhalation studies, using two of the suspensions, were conducted for aerosols generated by a pressurized nebulizer. NiO samples induced PMN responses 3 days after instillation according to the surface area doses, but not the mass doses, as has been reported in many studies. When the same NiO samples were tested in a 4-week inhalation and intratracheal instillation, the amount of pulmonary deposition of the sample after the 4-week inhalation, and an intratracheally instilled dose about ten-times higher, induced similar PMN responses 3 days after termination of inhalation and instillation. Using the relationship between these responses to 4-week inhalation and intratracheal instillation, it may be possible to estimate what aerosol concentrations of other nanomaterials might cause the same responses of PMN production as intratracheal instillation tests.
Inhalation Toxicology 01/2013; 25(1):29-36. · 1.92 Impact Factor
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Yasuo Morimoto,
Masami Hirohashi,
Akira Ogami,
Takako Oyabu,
Toshihiko Myojo,
Masayoshi Hashiba,
Yohei Mizuguchi,
Tatsunori Kambara,
Byeong Woo Lee,
Etsushi Kuroda,
Isamu Tanaka
[show abstract]
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ABSTRACT: OBJECTIVE: In our previous study, we reported that the micron-sized nickel oxide nanoparticle agglomerates induced neutrophil infiltration and the gene expression of the cytokine-induced neutrophil chemoattractant (CINC)-2αβ in a rat lung. In this study, we examined the expression of the CINCs family in the lung using the same rat model exposed to micron-sized nickel oxide nanoparticle agglomerates. METHODS: The count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 μm (primary diameter: 8.41 nm). Male Wistar rats received an intratracheal instillation of 1 mg (3.3 mg/kg) of nickel oxide nanoparticles and were dissected at 3 days, 1 week, 1 month, 3 months, and 6 months after the instillation. The negative control group received an instillation of saline. The concentration of CINC-1 in the lung and the bronchoalveolar lavage fluid (BALF), CINC-2αβ in the BALF, and CINC-3 in the lung and the BALF was examined. RESULTS: The concentration of CINC-1 was elevated at 3 days, 3 months, and 6 months in the lung tissue and from 3 days to 6 months in the BALF. The concentration of CINC-2αβ was elevated from 3 days to 3 months in the BALF. The concentration of CINC-3 was also elevated at 3 days, 1 week, 3 months, and 6 months in the lung tissue. Infiltration of neutrophil and alveolar macrophage was observed mainly in the alveoli during the observed time period. CONCLUSION: These results suggest that CINC-1 to -3 were totally involved in the lung injury caused by micron-sized nickel oxide nanoparticle agglomerates.
Toxicology and Industrial Health 10/2012; · 1.42 Impact Factor
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ABSTRACT: Japan, U.S.A. and other foreign space agencies have plans for the construction of a lunar base and long-term stay of astronauts on the moon. The surface of the moon is covered by a thick layer of soil that includes fine particles called "lunar regolith", which is formed by meteorite impact and space weathering. Risk assessment of particulate matter on the moon is important for astronauts working in microgravity on the moon. However, there are few investigations about the biological influences of lunar regolith. Especially, there is no investigation about allergic activity to lunar regolith. The main chemical components of lunar regolith are SiO2, Al2O3, CaO, FeO, etc. Of particular interest, approximately 50% of lunar regolith consists of SiO2. There is a report that the astronauts felt hay fever-like symptoms from the inhalation of the lunar regolith. Yellow sand, whose chemical components are similar to lunar regolith, enhances allergenic reactions, suggesting the possibility that lunar regolith has an adjuvant-like activity. Although intraperitoneal administration of lunar regolith with ovalbumin to mouse did not show enhancement of allergenic reactions, further evaluation of lunar regolith's potential to exacerbate the effects of allergies is essential for development of the moon.
Journal of UOEH 09/2012; 34(3):237-43.
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Tadashi Murase,
Hiroko Kitamura,
Takeshi Kochi,
Niina Terunuma,
Shizuka Kurosaki,
Kouichi Hata,
Nobuaki Yanagi,
Bungo Uchino,
Kayo Kitahara, Yasuo Morimoto,
Hiroshi Kasai,
Toshio Sasaki,
Akira Ogami,
Toshiaki Higashi
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ABSTRACT: Abstract Background: Interleukins, interferons and oxidative DNA products are important biomarkers assessing the inflammations and tissue damages caused by toxic materials in the body. We tried to evaluate distributions, reference values and age related changes of blood levels of inflammatory cytokines, C-reactive protein (CRP), IgE and urine levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) among workers in a cohort study evaluating the health influences of toner particles. Methods: A total of 1366 male workers under age 50 years (age 19-49 years; 718 exposed and 648 not exposed to toner particles) in a cross sectional study of 1614 (categorized as 809 exposed and 805 not exposed, age 19-59 years) workers in a photocopier company has been followed prospectively as the cohort. Blood levels of interleukin (IL)-4, IL-6, IL-8, interferon-γ (IFN-γ), CRP, IgE and urine 8-OHdG were measured annually for 5 years. Results: Reference values of the biomarkers are; CRP: 0.01-0.63×10-2g/L, IgE: 6-1480 IU/mL, IL-4: 2.6-76.1 pg/mL, IL-6: 0.4-4.9 pg/mL and 8-OHdG: 1.5-8.2 ng/mgCr. We could not evaluate reference values for IL-8 and IFN-γ because most of the values were below the sensitivity limits (2.0 pg/mL and 0.1 IU/mL, respectively). There were no differences of the biomarker levels between the toner exposed and the control workers. We observed a statistically significant age related decrease of serum IL-4 levels. Conclusions: This is the first report assessing the distributions and reference values of inflammatory biomarker levels in a large scaled cohort. We observed age related changes of some of the biomarkers. We could not detect any differences of the studied biomarker values between the toner exposed and the control workers.
Clinical Chemistry and Laboratory Medicine 08/2012; · 2.15 Impact Factor
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Masanori Horie,
Hiroko Fukui,
Shigehisa Endoh,
Junko Maru,
Arisa Miyauchi,
Mototada Shichiri,
Katsuhide Fujita,
Etsuo Niki,
Yoshihisa Hagihara,
Yasukazu Yoshida, Yasuo Morimoto,
Hitoshi Iwahashi
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ABSTRACT: The aim of the present study is to understand the association between metal ion release from nickel oxide (NiO) nanoparticles and induction of oxidative stress in the lung. NiO nanoparticles have cytotoxic activity through nickel ion release and subsequent oxidative stress. However, the interaction of oxidative stress and nickel ion release in vivo is still unclear. In the present study, we examined the effect of metal ion release on oxidative stress induced by NiO nanoparticles. Additionally, nano and fine TiO(2) particles as insoluble particles were also examined. Rat lung was exposed to NiO and TiO(2) nanoparticles by intratracheal instillation. The NiO nanoparticles released Ni(2+) in dispersion. Bronchoalveolar lavage fluid (BALF) was collected at 1, 24, 72 h and 1 week after instillation. The lactate dehydrogenase (LDH) and HO-1 levels were elevated at 24 and 72 h after instillation in the animals exposed to the NiO nanoparticles. On the other hand, total hydroxyoctadecadienoic acid (tHODE), which is an oxidative product of linoleic acid, as well as SP-D and α-tochopherol levels were increased at 72 h and 1 week after instillation. Fine NiO particles, and nano and fine TiO(2) particles did not show lung injury or oxidative stress from 1 h to 1 week after instillation. These results suggest that Ni(2+) release is involved in the induction of oxidative stress by NiO nanoparticles in the lung. Ni(2+) release from NiO nanoparticles is an important factor inoxidative stress-related toxicity, not only in vitro but also in vivo.
Inhalation Toxicology 06/2012; 24(7):391-400. · 1.92 Impact Factor
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ABSTRACT: Although the demand for nanomaterials has grown, researchers have not conclusively determined the effects of nanomaterials on the human body. To understand the effects of nanomaterials on occupational health, we need to estimate the respiratory toxicity of nanomaterials through inhalation studies, intratracheal instillation studies, and pharyngeal aspiration studies. The discrepancies observed among these studies tend to result from differences in the physiochemical properties of nanomaterials, such as aggregation and dispersion. Therefore, in all toxicity studies, identification of the physicochemical properties of nanomaterials is essential. This Account reviews the inhalation toxicity of manufactured nanomaterials and compares them with inhalation and intratracheal instillation studies of well-characterized fullerene and carbon nanotubes. In many reports, pulmonary inflammation and injury served as pulmonary endpoints for the inhalation toxicity. To assess pulmonary inflammation, we examined neutrophil and macrophage infiltration in the alveolar and/or interstitial space, and the expression of the neutrophil and/or monocyte chemokines. We also reported the release of lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in the bronchoalveolar lavage fluid (BALF), the expression of oxidative stress-related genes characteristic of lung injury, and the presence of granulomatous lesion and pulmonary fibrosis. In the inhalation and intratracheal instillation studies of well-characterized fullerenes, exposure to fullerene did not induce pulmonary inflammation or transient inflammation. By contrast, in an inhalation study, a high concentration of multiwall carbon nanotubes (MWCNTs) and single-wall carbon nanotubes (SWCNTs) induced neutrophil inflammation or granulomatous formations in the lung, and intratracheal instillation of MWCNTs and SWCNTs induced persistent inflammation in the lung. Among the physicochemical properties of carbon nanotubes, the increased surface area is associated with inflammatory activity as measured by the increase in the rate of neutrophils measured in bronchoalveolar lavage fluid. Metal impurities such as iron and nickel enhanced the pulmonary toxicity of carbon nanotubes, and SWCNTs that included an amorphous carbon induced multifocal granulomas in the lung while purer SWCNTs did not. The aggregation state also affects pulmonary response: Exposure to well-dispersed carbon nanotubes led to the thickening of the alveolar wall and fewer granulomatous lesions in the lung, while agglomerated carbon nanotubes produced granulomatous inflammation. The values of the acceptable exposure concentration in some countries were based on the data of subacute and subchronic inhalation and intratracheal instillation studies of well-characterized fullerene and carbon nanotubes. In Japan, the acceptable exposure concentration of fullerene is 0.39 mg/m(3). In Europe, the proposal concentration is 44.4 μg/m(3) for acute toxicity and 0.27 μg/m(3) for chronic toxicity. The proposal acceptable exposure concentrations of carbon nanotubes are 0.03, 0.05, and 0.007 mg/m(3) in Japan, Europe, and the United States, respectively.
Accounts of Chemical Research 05/2012; · 21.64 Impact Factor
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Toshihiko Myojo,
Takako Oyabu,
Akira Ogami,
Masami Hirohashi,
Masahiro Murakami,
Makoto Yamamoto,
Motoi Todoroki,
Chikara Kadoya,
Kenichiro Nishi,
Sayumi Yamasaki, Yasuo Morimoto,
Isamu Tanaka,
Manabu Shimada,
Shigehisa Endoh
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ABSTRACT: Fullerenes are interesting carbon nanomaterials with several forms of C60, C70, C76, and more molecules. However, little is known of the risk associated with their exposure. Inhalation is considered the most
significant route of exposure to nanoparticles suspended in air, so we need suitable analytical methods of aerosol particles
containing the fullerenes. Usually, fullerenes dissolved in organic solvents are analyzed by high performance liquid chromatography
(HPLC) technique. For aerosol samples on filters, any extraction process must be conducted before HPLC analysis. In this study,
we used a carbon aerosol analyzer for diesel exhaust particulates to determine fullerene amount in aerosol particles without
any extraction process. The filter samples were directly analyzed by this instrument within half hour. Our method was applied
for aerosols of C60 with dispersant, which was sampled from a whole body exposure chamber for rats. Inhalation study was conducted for 4weeks,
5days a week, 6h a day, and one filter sample was obtained from more than 5h sampling of 6h exposure. Average concentration
of 19 samples of C60 aerosols for 4week inhalation was 0.12±0.03mg/m3 calculated from total aerosol mass and weight fraction of C60 and 0.13±0.03mg/m3 measured by the carbon aerosol analyzer. Minimum determination limit of this method was <1μg for filter samples. The limit
was a hundred times higher than the HPLC technique but better than the gravimetric method using microbalance for filter samples.
KeywordsFullerene–Carbon aerosol analyzer–Elemental carbon–Nanoparticle–Inhalation–In vivo study–EHS–Manufactured nanomaterials
Journal of Nanoparticle Research 04/2012; 13(5):2063-2071. · 3.29 Impact Factor
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ABSTRACT: Nanoparticles are defined as particles whose diameter is 1-100 nm. Many investigations about the toxicology of nanoparticles have been reported recently. The toxicity of nanoparticles has been examined both in vivo and in vitro and many results are being achieved. However, the results of in vivo and in vitro examinations are sometimes different. According to the in vitro examinations, it is suggested that solubility, adsorption ability and surface activity are involved in the cytotoxicity of nanoparticles. On the other hand, in in vivo, clearance is an important factor in the lung toxicity of nanoparticles. In the hazard assessment of nanoparticles, in vivo and in vitro examinations are necessary for an accurate evaluation of their biological influences, including the toxic mechanisms.
Journal of UOEH 03/2012; 34(1):57-64.
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ABSTRACT: Fullerene (C60) is a newly generated nanoparticle that has a soccer-ball structure with 60 carbon atoms. Fullerenes are expected to have a multitude of uses, for example as energy device materials or information technology materials. The biological effects of nanoparticles are now being discussed, and there are ongoing animal studies using various nanoparticles. Here we review some reports about the toxicity of C60, and in addition we present the results of our 2-year follow up studies of instillation and inhalation of C60 via the trachea.
Journal of UOEH 03/2012; 34(1):65-75.
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ABSTRACT: Nickel oxide with two different particle sizes, micron size (NiO) and submicron size (nNiOm), as well as crystalline silica as a positive control and titanium dioxide as a negative control, were intratracheally instilled in rats and the phospholipid concentration and the protein concentration and surface tension of bronchoalveolar lavage fluid (BALF), which are used in surfactant assessment, were measured to see if they could be effective biomarkers in toxicity assessment. The results showed that the NiO instilled group showed no significant difference compared to the control group throughout the observation period. In contrast, a significant difference was found in the nNiOm instilled group compared to the control group throughout the observation period. Moreover, a significant difference was found in the crystalline silica instilled group for each measurement compared to the control group while for the titanium dioxide group, almost no significant difference was found. These results indicate that submicronsized particles of nickel oxide with smaller median diameters potentially have a stronger biological effect than micron size particles. They also indicate that screening can be done by measuring the phospholipid concentration and the protein concentration and surface tension of BALF.
Industrial Health 12/2011; 50(1):31-6. · 0.94 Impact Factor
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Takako Oyabu,
Toshihiko Myojo, Yasuo Morimoto,
Akira Ogami,
Masami Hirohashi,
Makoto Yamamoto,
Motoi Todoroki,
Yohei Mizuguchi,
Masayoshi Hashiba,
Byeong Woo Lee, [......],
Kunio Uchida,
Shigehisa Endoh,
Norihiro Kobayashi,
Kazuhiro Yamamoto,
Katsuhide Fujita,
Kohei Mizuno,
Masaharu Inada,
Tetsuya Nakazato,
Junko Nakanishi,
Isamu Tanaka
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ABSTRACT: It is important to conduct a risk assessment that includes hazard assessment and exposure assessment for the safe production and handling of newly developed nanomaterials. We conducted an inhalation study of a multi-wall carbon nanotube (MWCNT) as a hazard assessment. Male Wistar rats were exposed to well-dispersed MWCNT for 4 weeks by whole body inhalation. The exposure concentration in the chamber was 0.37 ± 0.18 mg/m³. About 70% of the MWCNTs in the chamber were single fiber. The geometric mean diameter (geometric standard deviation, GSD) and geometric mean length (GSD) of the aerosolized MWCNTs in the chamber were 63 nm (1.5) and 1.1 μm (2.7), respectively. The amounts of MWCNT deposited in the rat lungs were determined by the X-ray diffraction method and elemental carbon analysis. The average deposited amounts at 3 days after the inhalation were 68 μg/lung by the X-ray diffraction method and 76 μg/lung by elemental carbon analysis. The calculated deposition fractions were 18% and 20% in each analysis. The amount of retained MWCNT in the lungs until 3 months after the inhalation decreased exponentially and the calculated biological half times of MWCNT were 51 days and 54 days, respectively. The clearance was not delayed, but a slight increase in lung weight at 3 days after the inhalation was observed.
Inhalation Toxicology 11/2011; 23(13):784-91. · 1.92 Impact Factor
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ABSTRACT: We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by morphological and immunohistochemical examination of intra-alveolar cells and alveolar macrophages in Clara cell-ablated mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg). The mice were then exposed to crystalline silica (Min-U-Sil-5, 97.1 ± 9.5 mg/m³, 6 hours/day, 5 days/week) for up to two weeks. The lungs were assessed by morphometry, as well as by immunohistochemistry of CD36, lectin-like oxygenated low-density lipoprotein receptor (LOX)-1, and matrix metalloproteinases (MMPs) -2, -9 and -12. There was a significantly greater number of intra-alveolar cells in Clara cell-ablated mouse groups than in wild-type mouse groups that were exposed to crystalline silica. A marked number of foamy alveolar macrophages were only detected in the Clara cell-ablated group exposed to crystalline silica, indicating that Clara cells inhibit infiltration and foam cell formation of alveolar macrophages. Immunohistochemical analysis indicated that foamy alveolar macrophages in the Clara cell-ablated group that inhaled crystalline silica overexpress CD36 and LOX-1, indicating upregulation of scavenger receptors of alveolar macrophages. These cells also express MMP-2, -9 and -12, suggesting increased gelatinolytic and elastolytic activities. Our findings suggest that Clara cells not only inhibit infiltration of alveolar macrophages but also their phagocytotic and gelatinolytic functions in silica-induced pulmonary injury.
Inhalation Toxicology 10/2011; 23(12):736-44. · 1.92 Impact Factor
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Yasuo Morimoto,
Masami Hirohashi,
Norihiro Kobayashi,
Akira Ogami,
Masanori Horie,
Takako Oyabu,
Toshihiko Myojo,
Masayoshi Hashiba,
Yohei Mizuguchi,
Tatsunori Kambara,
Byeong Woo Lee,
Etsushi Kuroda,
Manabu Shimada,
Wei-Ning Wang,
Kohei Mizuno,
Kazuhiro Yamamoto,
Katsuhide Fujita,
Junko Nakanishi,
Isamu Tanaka
[show abstract]
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ABSTRACT: Abstract Single-wall carbon nanotubes (SWCNTs) were well-dispersed by ultrasonication to conduct an inhalation study. SWCNTs were generated using a pressurised nebuliser with liquid suspension of SWCNTs. Wistar rats were exposed to the well-dispersed SWCNT (diameter of bundle: 0.2 μm; length of bundle: 0.7 μm) for 4 weeks. The low and high mass concentrations of SWCNTs were 0.03 ± 0.003 and 0.13 ± 0.03 mg/m(3), respectively. The rats were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. There were no increases of total cell or neutrophil counts in the bronchoalveolar lavage fluid (BALF), or the concentration of cytokine-induced neutrophil chemoattractant in the lungs or BALF in both the high and low concentration-exposed groups. Pulmonary infiltration of neutrophils was not observed in either exposed group throughout the observation period. Well-dispersed SWCNT did not induce neutrophil inflammation in the lung under the conditions in the present study.
Nanotoxicology 09/2011; 6:766-75. · 5.76 Impact Factor
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Masanori Horie,
Haruhisa Kato,
Shigehisa Endoh,
Katsuhide Fujita,
Keiko Nishio,
Lilian Kaede Komaba,
Hiroko Fukui,
Ayako Nakamura,
Arisa Miyauchi,
Tetsuya Nakazato,
Shinichi Kinugasa,
Yasukazu Yoshida,
Yoshihisa Hagihara, Yasuo Morimoto,
Hitoshi Iwahashi
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ABSTRACT: Platinum nanoparticles have industrial application, for example in catalysis, and are used in consumer products such as cosmetics and supplements. Therefore, among the many nanoparticles, platinum is one of the more accessible nanoparticles for consumers. Most platinum nanoparticles that are used in cosmetics and supplements which have an anti-oxidant activity are modified particles. However, the cellular influences of pristine platinum nanoparticles are still unclear, although it has been reported that platinum nanoparticles induce oxidative stress. In this study, we investigated the cellular influences induced by pure pristine platinum nanoparticles. Platinum nanoparticles of 100% purity were dispersed in a cell culture medium and stable medium dispersion was obtained. The platinum nanoparticle medium dispersion was applied to two kinds of cultured cells, A549 and HaCaT cells, and the cellular influences were examined. Cell viability (MTT assay), cell proliferation (clonogenic assay), apoptosis induction (caspase-3 activity), intracellular ROS level (DCFH assay), and lipid peroxidation level (DPPP assay) were measured as markers of cellular influences. Transmission electron microscope observation showed cellular uptake of platinum nanoparticles. However, the platinum nanoparticles did not drive any markers. It is known that some metal oxide nanoparticles such as NiO and CuO show severe cytotoxicity via metal ion release. Compared with these toxic nanoparticles, the platinum nanoparticles used in this study did not release platinum ions into the culture media. These results suggest that the physically and chemically inactive cellular influences of platinum nanoparticles are small.
Metallomics 08/2011; 3(11):1244-52. · 3.90 Impact Factor
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Yasuo Morimoto,
Masami Hirohashi,
Akira Ogami,
Takako Oyabu,
Toshihiko Myojo,
Motoi Todoroki,
Makoto Yamamoto,
Masayoshi Hashiba,
Yohei Mizuguchi,
Byeong Woo Lee, [......],
Katsuhide Fujita,
Shigehisa Endoh,
Kunio Uchida,
Norihiro Kobayashi,
Kohei Mizuno,
Masaharu Inada,
Hiroaki Tao,
Tetsuya Nakazato,
Junko Nakanishi,
Isamu Tanaka
[show abstract]
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ABSTRACT: Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting mainly of individual tubes, were used for intratracheal instillation and inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups, and presence of small granulomatous lesion and persistent neutrophil infiltration in the high-dose groups. In the inhalation study, rats were exposed to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inhalation exposures delivered less amounts of MWCNTs into the lungs, and therefore less pulmonary inflammation responses was observed, as compared to intratracheal instillation. The results of our study show that well-dispersed MWCNT can produce pulmonary lesions, including inflammation.
Nanotoxicology 06/2011; 6(6):587-99. · 5.76 Impact Factor
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Yasuko Obata, Yasuo Morimoto,
Masami Hirohashi,
Akira Ogami,
Takako Oyabu,
Toshihiko Myojo,
Shoko Kawanami,
Seichi Horie,
Hiroko Nagatomo,
Masahiro Murakami,
Isamu Tanaka
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ABSTRACT: Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to potassium octatitanate whiskers (PT1), which is one of the asbestos substitutes.
Male Wistar rats were administered 1 mg or 2 mg PT1 suspended in saline by a single intratracheal instillation and were sacrificed after recovery for 3 days, 1 wk, 1 mo, 3 mo or 6 mo. Gene expression of HO-1 protein and mRNA and immunostaining were investigated in rat lungs.
HO-1 protein expression was increased from 3 days to 1 mo and at 6 mo in the 1 or 2 mg PT1-exposed groups, and the gene expression of HO-1 mRNA was also increased at 3 days and from 1 mo to 6 mo. HO-1-positive cells were mainly found in the alveolar macrophages and the bronchial epithelial cells in immunostaining.
These findings suggest that HO-1 is involved in lung damage caused by PT1.
Journal of Occupational Health 06/2011; 53(4):267-73. · 1.55 Impact Factor
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Akira Ogami,
Kazuhiro Yamamoto, Yasuo Morimoto,
Katsuhide Fujita,
Masami Hirohashi,
Takako Oyabu,
Toshihiko Myojo,
Kenichiro Nishi,
Chikara Kadoya,
Motoi Todoroki,
Makoto Yamamoto,
Masahiro Murakami,
Manabu Shimada,
Wei-Ning Wang,
Naohide Shinohara,
Shigehisa Endoh,
Kunio Uchida,
Junko Nakanishi,
Isamu Tanaka
[show abstract]
[hide abstract]
ABSTRACT: We evaluated the pulmonary pathological features of rats that received a single intratracheal instillation and a 4-week inhalation of a fullerene. We used fullerene C60 (nanom purple; Frontier Carbon Co. Ltd, Japan) in this study. Male Wistar rats received intratracheal dose of 0.1, 0.2, or 1 mg of C60, and were sacrificed at 3 days, 1 week, 1 month, 3 months, 6 months, and 12 months. In the inhalation study, Wistar rats received C60 or nickel oxide by whole-body inhalation for 6 h/day, 5 days/week, 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. During the observation period, no tumors or granulomas were observed in either study. Histopathological evaluation by the point counting method (PCM) showed that a high dose of C60 (1 mg) instillation led to a significant increase of areas of inflammation in the early phase (until 1 week). In the inhalation study of the C60-exposed group, PCM evaluation showed significant changes in the C60-exposed group only at 3 days after exposure; after 1 month, no significant changes were observed. The present study demonstrated that the pulmonary inflammation pattern after exposure to well-characterized C60 via both intratracheal and inhalation instillation was slight and transient. These results support our previous studies that showed C60 has no significant adverse effects in intratracheal and inhalation instillation studies.
06/2011; 23(7):407-416.
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Akira Ogami,
Kazuhiro Yamamoto, Yasuo Morimoto,
Katsuhide Fujita,
Masami Hirohashi,
Takako Oyabu,
Toshihiko Myojo,
Kenichiro Nishi,
Chikara Kadoya,
Motoi Todoroki,
Makoto Yamamoto,
Masahiro Murakami,
Manabu Shimada,
Wei-Ning Wang,
Naohide Shinohara,
Shigehisa Endoh,
Kunio Uchida,
Junko Nakanishi,
Isamu Tanaka
[show abstract]
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ABSTRACT: We evaluated the pulmonary pathological features of rats that received a single intratracheal instillation and a 4-week inhalation of a fullerene. We used fullerene C(60) (nanom purple; Frontier Carbon Co. Ltd, Japan) in this study. Male Wistar rats received intratracheal dose of 0.1, 0.2, or 1 mg of C(60), and were sacrificed at 3 days, 1 week, 1 month, 3 months, 6 months, and 12 months. In the inhalation study, Wistar rats received C(60) or nickel oxide by whole-body inhalation for 6 h/day, 5 days/week, 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. During the observation period, no tumors or granulomas were observed in either study. Histopathological evaluation by the point counting method (PCM) showed that a high dose of C(60) (1 mg) instillation led to a significant increase of areas of inflammation in the early phase (until 1 week). In the inhalation study of the C(60)-exposed group, PCM evaluation showed significant changes in the C(60)-exposed group only at 3 days after exposure; after 1 month, no significant changes were observed. The present study demonstrated that the pulmonary inflammation pattern after exposure to well-characterized C(60) via both intratracheal and inhalation instillation was slight and transient. These results support our previous studies that showed C(60) has no significant adverse effects in intratracheal and inhalation instillation studies.
Inhalation Toxicology 06/2011; 23(7):407-16. · 1.92 Impact Factor
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Toshihiko Myojo,
Takako Oyabu,
Akira Ogami, Yasuo Morimoto,
Kenichiro Nishi,
Chikara Kadoya,
Makoto Yamamoto,
Motoi Todoroki,
Yohei Mizuguchii,
Byeong Woo Lee,
Masayoshi Hashiba,
Tatsunori Kambara
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ABSTRACT: It is necessary to consider protective measures, such as dust respirators, against the inhalation of nanoparticle aerosols. Industrial hygienists and workers handling nanomaterials are concerned about the filteration performance of dust respirators in protecting against nanoparticles, the size of which is less than 100 nm. We developed a filteration performance evaluating system using titanium dioxide nanoparticle aerosols ranging from 15 to 220 nm in diameter. The system, which includes two models of DS1 class and four models of DS2 class, was used to measure the collection efficiencies of dust respirators. These tested dust respirators had been certified by the Japanese government. In the dust respirators, there were no samples that showed less collection efficiency than the standard certified collection efficiency (80% for DS1 and 95% for DS2).
Journal of UOEH 06/2011; 33(2):163-71.
