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Yasuo Morimoto - One of the best experts on this subject based on the ideXlab platform.

  • assessment of cytokine induced neutrophil chemoattractants as biomarkers for prediction of pulmonary toxicity of nanomaterials
    Nanomaterials, 2020
    Co-Authors: Taisuke Tomonaga, Manabu Shimada, Hiroto Izumi, Kazuhiro Yatera, Masaru Kubo, Byeongwoo Lee, Shingo Noguchi, Chinatsu Nishida, Takako Oyabu, Yasuo Morimoto
    Abstract:

    This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2 (P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after Intratracheal Instillation (0.2 and 1.0 mg) and inhalation exposure (0.32–10.4 mg/m3) of materials (NiO, CeO2, TiO2 (P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following Intratracheal Instillation of SiO2 as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both Intratracheal Instillation and inhalation exposure.

  • evaluation of pulmonary toxicity of zinc oxide nanoparticles following inhalation and Intratracheal Instillation
    International Journal of Molecular Sciences, 2016
    Co-Authors: Yasuo Morimoto, Manabu Shimada, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Kazuaki Kawai, Takako Oyabu, Masaru Kubo
    Abstract:

    We conducted inhalation and Intratracheal Instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received Intratracheal Instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the Instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal Instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the Intratracheal Instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

  • Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity
    International journal of molecular sciences, 2016
    Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kei Fujishima, Kazuhiro Yatera, Kazuhiro Yamamoto
    Abstract:

    Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by Intratracheal Instillation. We reviewed the effectiveness of Intratracheal Instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and Intratracheal Instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in Intratracheal Instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the Intratracheal Instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between Intratracheal Instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the Intratracheal Instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that Intratracheal Instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.

  • Intratracheal Instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression
    2016
    Co-Authors: Katsuhide Fujita, Masanori Horie, Yasuo Morimoto, Hiroko Fukui, Shigehisa Endoh, Akira Ogami, Makiko Fukuda, Kunio Uchida, Mototada Shichiri, Hitoshi Iwahashi
    Abstract:

    The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single Intratracheal Instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-Instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-Instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-Instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after Intratracheal Instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-Instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-Instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT Instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

  • pulmonary toxicity of well dispersed cerium oxide nanoparticles following Intratracheal Instillation and inhalation
    Journal of Nanoparticle Research, 2015
    Co-Authors: Yasuo Morimoto, Manabu Shimada, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Kazuaki Kawai, Takako Oyabu, Masaru Kubo
    Abstract:

    We performed inhalation and Intratracheal Instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the Intratracheal Instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the Instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal Instillation study were examined from 3 days to 3 months after the end of the exposure. The Intratracheal Instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

Takako Oyabu - One of the best experts on this subject based on the ideXlab platform.

  • assessment of cytokine induced neutrophil chemoattractants as biomarkers for prediction of pulmonary toxicity of nanomaterials
    Nanomaterials, 2020
    Co-Authors: Taisuke Tomonaga, Manabu Shimada, Hiroto Izumi, Kazuhiro Yatera, Masaru Kubo, Byeongwoo Lee, Shingo Noguchi, Chinatsu Nishida, Takako Oyabu, Yasuo Morimoto
    Abstract:

    This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2 (P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after Intratracheal Instillation (0.2 and 1.0 mg) and inhalation exposure (0.32–10.4 mg/m3) of materials (NiO, CeO2, TiO2 (P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following Intratracheal Instillation of SiO2 as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both Intratracheal Instillation and inhalation exposure.

  • Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials
    Particle and Fibre Toxicology, 2018
    Co-Authors: Taisuke Tomonaga, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Byeongwoo Lee, Takami Okada, Takako Oyabu, Takashi Marui, Ke-yong Wang, Masaru Kubo
    Abstract:

    Background In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed Intratracheal Instillation exposures (dose: 0.2–1.0 mg) and inhalation exposures (exposure concentration: 0.32–10.4 mg/m^3) using 9 and 4 nanomaterials with different toxicities, respectively. Based on those previous studies, we set Nickel oxide nanoparticles (NiO), cerium dioxide nanoparticles (CeO_2), multi wall carbon nanotubes with short or long length (MWCNT (S) and MWCNT (L)), and single wall carbon nanotube (SWCNT) as chemicals with high toxicity; and titanium dioxide nanoparticles (TiO_2 (P90) and TiO_2 (Rutile)), zinc oxide nanoparticles (ZnO), and toner with external additives including nanoparticles as chemicals with low toxicity. We measured the concentration of MPO in BALF samples from rats from 3 days to 6 months following a single Intratracheal Instillation, and from 3 days to 3 months after the end of inhalation exposure. Results Intratracheal Instillation of high toxicity NiO, CeO_2, MWCNT (S), MWCNT (L), and SWCNT persistently increased the concentration of MPO, and inhalation of NiO and CeO_2 increased the MPO in BALF. By contrast, Intratracheal Instillation of low toxicity TiO_2 (P90), TiO_2 (Rutile), ZnO, and toner increased the concentration of MPO in BALF only transiently, and inhalation of TiO_2 (Rutile) and ZnO induced almost no increase of the MPO. The concentration of MPO correlated with the number of total cells and neutrophils, the concentration of chemokines for neutrophils (cytokine-induced neutrophil chemoattractant (CINC)-1 and heme oxygenase (HO)-1), and the activity of released lactate dehydrogenase (LDH) in BALF. The results from the receiver operating characteristics (ROC) for the toxicity of chemicals by the concentration of MPO proteins in the Intratracheal Instillation and inhalation exposures showed that the largest areas under the curves (AUC) s in both examinations occurred at 1 month after exposure. Conclusion These data suggest that MPO can be a useful biomarker for the ranking of the pulmonary toxicity of nanomaterials, especially at 1 month after exposure, in both Intratracheal Instillation and inhalation exposure.

  • Additional file 1: of Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials
    2018
    Co-Authors: Taisuke Tomonaga, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Byeongwoo Lee, Takami Okada, Takako Oyabu, Takashi Marui, Ke-yong Wang, Masaru Kubo
    Abstract:

    Figure S1-S2. Relationship between MPO and inflammatory markers after Intratracheal Instillation or inhalation exposure. Figure S1: Relationship between MPO and inflammatory markers: (a) neutrophils, (b) percent of neutrophils in total cells, (c) total cell, (d) CINC-1, (e) HO-1 and (f) LDH versus MPO concentration in BALF after Intratracheal Instillation of inhaled chemicals. Values of ρ are Spearman’s rank correlation coefficient for each of the data. Figure S2. Relationship between MPO and inflammatory markers: (a) neutrophils, (b) percent of neutrophils in total cells, )c) total cell, (d) CINC-1, (e) HO-1 and (f) LDH versus MPO concentration in BALF after inhalation exposure. Values of ρ are Spearman’s rank correlation coefficient for each of the data. (DOCX 141 kb

  • Biopersistence of NiO and TiO2 Nanoparticles Following Intratracheal Instillation and Inhalation
    MDPI AG, 2017
    Co-Authors: Takako Oyabu, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Taisuke Tomonaga, Kazuaki Kawai, Byeongwoo Lee, Takami Okada, Manabu Shimada
    Abstract:

    The hazards of various types of nanoparticles with high functionality have not been fully assessed. We investigated the usefulness of biopersistence as a hazard indicator of nanoparticles by performing inhalation and Intratracheal Instillation studies and comparing the biopersistence of two nanoparticles with different toxicities: NiO and TiO2 nanoparticles with high and low toxicity among nanoparticles, respectively. In the 4-week inhalation studies, the average exposure concentrations were 0.32 and 1.65 mg/m3 for NiO, and 0.50 and 1.84 mg/m3 for TiO2. In the Instillation studies, 0.2 and 1.0 mg of NiO nanoparticles and 0.2, 0.36, and 1.0 mg of TiO2 were dispersed in 0.4 mL water and instilled to rats. After the exposure, the lung burden in each of five rats was determined by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES) from 3 days to 3 months for inhalation studies and to 6 months for Instillation studies. In both the inhalation and Instillation studies, NiO nanoparticles persisted for longer in the lung compared with TiO2 nanoparticles, and the calculated biological half times (BHTs) of the NiO nanoparticles was longer than that of the TiO2 nanoparticles. Biopersistence also correlated with histopathological changes, inflammatory response, and other biomarkers in bronchoalveolar lavage fluid (BALF) after the exposure to nanoparticles. These results suggested that the biopersistence is a good indicator of the hazards of nanoparticles

  • evaluation of pulmonary toxicity of zinc oxide nanoparticles following inhalation and Intratracheal Instillation
    International Journal of Molecular Sciences, 2016
    Co-Authors: Yasuo Morimoto, Manabu Shimada, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Kazuaki Kawai, Takako Oyabu, Masaru Kubo
    Abstract:

    We conducted inhalation and Intratracheal Instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received Intratracheal Instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the Instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal Instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the Intratracheal Instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

Toshihiko Myojo - One of the best experts on this subject based on the ideXlab platform.

  • Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials
    Particle and Fibre Toxicology, 2018
    Co-Authors: Taisuke Tomonaga, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Byeongwoo Lee, Takami Okada, Takako Oyabu, Takashi Marui, Ke-yong Wang, Masaru Kubo
    Abstract:

    Background In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed Intratracheal Instillation exposures (dose: 0.2–1.0 mg) and inhalation exposures (exposure concentration: 0.32–10.4 mg/m^3) using 9 and 4 nanomaterials with different toxicities, respectively. Based on those previous studies, we set Nickel oxide nanoparticles (NiO), cerium dioxide nanoparticles (CeO_2), multi wall carbon nanotubes with short or long length (MWCNT (S) and MWCNT (L)), and single wall carbon nanotube (SWCNT) as chemicals with high toxicity; and titanium dioxide nanoparticles (TiO_2 (P90) and TiO_2 (Rutile)), zinc oxide nanoparticles (ZnO), and toner with external additives including nanoparticles as chemicals with low toxicity. We measured the concentration of MPO in BALF samples from rats from 3 days to 6 months following a single Intratracheal Instillation, and from 3 days to 3 months after the end of inhalation exposure. Results Intratracheal Instillation of high toxicity NiO, CeO_2, MWCNT (S), MWCNT (L), and SWCNT persistently increased the concentration of MPO, and inhalation of NiO and CeO_2 increased the MPO in BALF. By contrast, Intratracheal Instillation of low toxicity TiO_2 (P90), TiO_2 (Rutile), ZnO, and toner increased the concentration of MPO in BALF only transiently, and inhalation of TiO_2 (Rutile) and ZnO induced almost no increase of the MPO. The concentration of MPO correlated with the number of total cells and neutrophils, the concentration of chemokines for neutrophils (cytokine-induced neutrophil chemoattractant (CINC)-1 and heme oxygenase (HO)-1), and the activity of released lactate dehydrogenase (LDH) in BALF. The results from the receiver operating characteristics (ROC) for the toxicity of chemicals by the concentration of MPO proteins in the Intratracheal Instillation and inhalation exposures showed that the largest areas under the curves (AUC) s in both examinations occurred at 1 month after exposure. Conclusion These data suggest that MPO can be a useful biomarker for the ranking of the pulmonary toxicity of nanomaterials, especially at 1 month after exposure, in both Intratracheal Instillation and inhalation exposure.

  • Additional file 1: of Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials
    2018
    Co-Authors: Taisuke Tomonaga, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Byeongwoo Lee, Takami Okada, Takako Oyabu, Takashi Marui, Ke-yong Wang, Masaru Kubo
    Abstract:

    Figure S1-S2. Relationship between MPO and inflammatory markers after Intratracheal Instillation or inhalation exposure. Figure S1: Relationship between MPO and inflammatory markers: (a) neutrophils, (b) percent of neutrophils in total cells, (c) total cell, (d) CINC-1, (e) HO-1 and (f) LDH versus MPO concentration in BALF after Intratracheal Instillation of inhaled chemicals. Values of ρ are Spearman’s rank correlation coefficient for each of the data. Figure S2. Relationship between MPO and inflammatory markers: (a) neutrophils, (b) percent of neutrophils in total cells, )c) total cell, (d) CINC-1, (e) HO-1 and (f) LDH versus MPO concentration in BALF after inhalation exposure. Values of ρ are Spearman’s rank correlation coefficient for each of the data. (DOCX 141 kb

  • Biopersistence of NiO and TiO2 Nanoparticles Following Intratracheal Instillation and Inhalation
    MDPI AG, 2017
    Co-Authors: Takako Oyabu, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Taisuke Tomonaga, Kazuaki Kawai, Byeongwoo Lee, Takami Okada, Manabu Shimada
    Abstract:

    The hazards of various types of nanoparticles with high functionality have not been fully assessed. We investigated the usefulness of biopersistence as a hazard indicator of nanoparticles by performing inhalation and Intratracheal Instillation studies and comparing the biopersistence of two nanoparticles with different toxicities: NiO and TiO2 nanoparticles with high and low toxicity among nanoparticles, respectively. In the 4-week inhalation studies, the average exposure concentrations were 0.32 and 1.65 mg/m3 for NiO, and 0.50 and 1.84 mg/m3 for TiO2. In the Instillation studies, 0.2 and 1.0 mg of NiO nanoparticles and 0.2, 0.36, and 1.0 mg of TiO2 were dispersed in 0.4 mL water and instilled to rats. After the exposure, the lung burden in each of five rats was determined by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES) from 3 days to 3 months for inhalation studies and to 6 months for Instillation studies. In both the inhalation and Instillation studies, NiO nanoparticles persisted for longer in the lung compared with TiO2 nanoparticles, and the calculated biological half times (BHTs) of the NiO nanoparticles was longer than that of the TiO2 nanoparticles. Biopersistence also correlated with histopathological changes, inflammatory response, and other biomarkers in bronchoalveolar lavage fluid (BALF) after the exposure to nanoparticles. These results suggested that the biopersistence is a good indicator of the hazards of nanoparticles

  • evaluation of pulmonary toxicity of zinc oxide nanoparticles following inhalation and Intratracheal Instillation
    International Journal of Molecular Sciences, 2016
    Co-Authors: Yasuo Morimoto, Manabu Shimada, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Kazuaki Kawai, Takako Oyabu, Masaru Kubo
    Abstract:

    We conducted inhalation and Intratracheal Instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received Intratracheal Instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the Instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal Instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the Intratracheal Instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

  • comparison of the pulmonary oxidative stress caused by Intratracheal Instillation and inhalation of nio nanoparticles when equivalent amounts of nio are retained in the lung
    Antioxidants, 2016
    Co-Authors: Masanori Horie, Toshihiko Myojo, Hiroto Izumi, Yukiko Yoshiura, Taisuke Tomonaga, Masaru Kubo, Byeongwoo Lee, Takami Okada, Takako Oyabu, Manabu Shimada
    Abstract:

    NiO nanoparticles were administered to rat lungs via Intratracheal Instillation or inhalation. During pulmonary toxicity caused by NiO nanoparticles, the induction of oxidative stress is a major factor. Both Intratracheal Instillation and inhalation of NiO nanoparticles induced pulmonary oxidative stress. The oxidative stress response protein, heme oxygenase-1 (HO-1), was induced by the administration of NiO nanoparticles at both the protein and gene expression level. Additionally, certain oxidative-stress markers in the lung, such as 8-iso-prostaglandin F2α, thioredoxin, and inducible nitric oxide synthase were increased. Furthermore, the concentration of myeloperoxidase (MPO) in the lung was also increased by the administration of NiO nanoparticles. When the amount of NiO in the lung is similar, the responses against pulmonary oxidative stress of Intratracheal Instillation and inhalation are also similar. However, the state of pulmonary oxidative stress in the early phase was different between Intratracheal Instillation and inhalation, even if the amount of NiO in the lung was similar. Inhalation causes milder oxidative stress than that caused by Intratracheal Instillation. On evaluation of the nanoparticle-induced pulmonary oxidative stress in the early phase, we should understand the different states of oxidative stress induced by Intratracheal Instillation and inhalation.

Akira Ogami - One of the best experts on this subject based on the ideXlab platform.

  • Intratracheal Instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression
    2016
    Co-Authors: Katsuhide Fujita, Masanori Horie, Yasuo Morimoto, Hiroko Fukui, Shigehisa Endoh, Akira Ogami, Makiko Fukuda, Kunio Uchida, Mototada Shichiri, Hitoshi Iwahashi
    Abstract:

    The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single Intratracheal Instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-Instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-Instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-Instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after Intratracheal Instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-Instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-Instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT Instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

  • comparison of dose response relations between 4 week inhalation and Intratracheal Instillation of nio nanoparticles using polimorphonuclear neutrophils in bronchoalveolar lavage fluid as a biomarker of pulmonary inflammation
    Inhalation Toxicology, 2013
    Co-Authors: Yohei Mizuguchi, Toshihiko Myojo, Motoi Todoroki, Makoto Yamamoto, Masayoshi Hashiba, Kenichiro Nishi, Chikara Kadoya, Byeongwoo Lee, Takako Oyabu, Akira Ogami
    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 response...

  • pulmonary toxicity of well dispersed multi wall carbon nanotubes following inhalation and Intratracheal Instillation
    Nanotoxicology, 2012
    Co-Authors: Yasuo Morimoto, Toshihiko Myojo, Motoi Todoroki, Makoto Yamamoto, Masayoshi Hashiba, Yohei Mizuguchi, Takako Oyabu, Masami Hirohashi, Akira Ogami, Etsushi Kuroda
    Abstract:

    AbstractMulti-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/m3 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 inflamma...

  • inflammogenic effect of well characterized fullerenes in inhalation and Intratracheal Instillation studies
    Particle and Fibre Toxicology, 2010
    Co-Authors: Yasuo Morimoto, Toshihiko Myojo, Motoi Todoroki, Makoto Yamamoto, Kenichiro Nishi, Chikara Kadoya, Takako Oyabu, Masami Hirohashi, Akira Ogami, Masahiro Murakami
    Abstract:

    We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an Intratracheal Instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the Intratracheal Instillation study. The reference material was nickel oxide in distilled water. Wistar male rats Intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 ± 5 nm; 0.12 ± 0.03 mg/m3; 6 hours/days for 5 days/week) for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs) were examined in rat lungs in both studies. In the Intratracheal Instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2αβ and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2αβ and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2αβ and-3 in the fullerene group. These data in Intratracheal Instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

  • expression of cytokine induced neutrophil chemoattractant in rat lungs by Intratracheal Instillation of nickel oxide nanoparticles
    Inhalation Toxicology, 2009
    Co-Authors: Kenichiro Nishi, Yasuo Morimoto, Toshihiko Myojo, Motoi Todoroki, Makoto Yamamoto, Masahiro Murakami, Chikara Kadoya, Takako Oyabu, Akira Ogami, Masami Hirohashi
    Abstract:

    Since nanoparticles easily agglomerate to form larger particles, it is important to maintain the size of their agglomerates at the nano-level to evaluate the harmful effect of the nanoparticles. We prevented agglomeration of nickel oxide nanoparticles by ultrasound diffusion and filtration, established an acute exposure model using animals, and examined inflammation and chemokine expression. The mass median diameter of nickel oxide nanoparticle agglomerates suspended in distilled water for Intratracheal Instillation was 26 nm (8.41 nm weighted average surface primary diameter). Male Wistar rats received Intratracheal Instillation of nickel oxide nanoparticles at 0.1 mg (0.33 mg/kg) or 0.2 mg (0.66 mg/kg), and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after the Instillation. The control group received Intratracheal Instillation of distilled water. Three chemokines (cytokine-induced neutrophil chemoattractant-1 (CINC-1), CINC-2alphabeta, and CINC-3) in the lung tissue and bronchoalveolar lavage fluid (BALF) were determined by quantitative measurement of protein by ELISA. Both CINC-1 and CINC-2alphabeta concentration was elevated from day 3 to 3 months in lung tissue and from day 3 to 6 months in BALF. On the other hand, CINC-3 was elevated on day 3 in both lung tissue and BALF, and then decreased. The total cell and neutrophil counts in BALF were increased from day 3 to 3 months. In lung tissue, infiltration of mainly neutrophils and alveolar macrophages was observed from day 3 to 6 months in alveoli. These results suggest that CINC was involved in lung injury by nickel oxide nanoparticles.

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  • in vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following Intratracheal Instillation in rats
    Regulatory Toxicology and Pharmacology, 2012
    Co-Authors: Masato Naya, Norihiro Kobayashi, Sawako Kasamoto, Masahito Fukumuro, Shigeaki Takami, Makoto Hayashi, Madoka Nakajima, Junko Nakanishi
    Abstract:

    Abstract Titanium dioxide (TiO 2 ) is widely used as a white pigment in paints, plastics, inks, paper, creams, cosmetics, drugs and foods. In the present study, the genotoxicity of anatase TiO 2 nanoparticles was evaluated in vivo using the comet assay after a single or repeated Intratracheal Instillation in rats. The nanoparticles were instilled Intratracheally at a dosage of 1.0 or 5.0 mg/kg body weight (single Instillation group) and 0.2 or 1.0 mg/kg body weight once a week for 5 weeks (repeated Instillation group) into male Sprague–Dawley rats. A positive control, ethyl methanesulfonate (EMS) at 500 mg/kg, was administered orally 3 h prior to dissection. Histopathologically, macrophages and neutrophils were detected in the alveolus of the lung in the 1.0 and 5.0 mg/kg TiO 2 groups. In the comet assay, there was no increase in % tail DNA in any of the TiO 2 groups. In the EMS group, there was a significant increase in % tail DNA compared with the negative control group. TiO 2 nanoparticles in the anatase crystal phase are not genotoxic following Intratracheal Instillation in rats.

  • pulmonary and systemic responses of highly pure and well dispersed single wall carbon nanotubes after Intratracheal Instillation in rats
    Inhalation Toxicology, 2011
    Co-Authors: Norihiro Kobayashi, Masato Naya, Kazuhiro Yamamoto, Makoto Ema, Kohei Mizuno, Junko Nakanishi
    Abstract:

    The present study was conducted to assess the pulmonary and systemic responses in rats after Intratracheal Instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2 mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1β and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after Instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the fore...

  • biological response and morphological assessment of individually dispersed multi wall carbon nanotubes in the lung after Intratracheal Instillation in rats
    Toxicology, 2010
    Co-Authors: Norihiro Kobayashi, Masato Naya, Makoto Ema, Shigehisa Endoh, Junko Maru, Kohei Mizuno, Junko Nakanishi
    Abstract:

    Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after a single Intratracheal Instillation in rats. The diameter and median length of the MWCNTs used in this study were approximately 60 nm and 1.5 μm, respectively. Groups of male Sprague-Dawley rats were Intratracheally instilled with 0.04, 0.2, or 1 mg/kg of the individually dispersed MWCNT suspension. After Instillation, the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers, and the lung, liver, kidney, spleen, and cerebrum were histopathologically evaluated at 3-day, 1-week, 1-month, 3-month, and 6-month post-exposure. Transient pulmonary inflammatory responses were observed only in the lungs of the group of rats exposed to 1 mg/kg of MWCNTs. Morphology of the instilled MWCNTs in the lungs of rats was assessed using light microscopy and transmission electron microscopy (TEM). Light microscopy examination revealed that MWCNTs deposited in the lungs of the rats were typically phagocytosed by the alveolar macrophages and these macrophages were consequently accumulated in the alveoli until 6-month post-exposure. The 400 TEM images obtained showed that all MWCNTs were located in the alveolar macrophages or macrophages in the interstitial tissues, and MWCNTs were not located in the cells of the interstitial tissues. There was no evidence of chronic inflammation, such as angiogenesis or fibrosis, induced by MWCNT Instillation. These results suggest that MWCNTs were being processed and cleared by alveolar macrophages.