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Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation.

Morimoto Y, Izumi H, Yoshiura Y, Tomonaga T, Oyabu T, Myojo T, Kawai K, Yatera K, Shimada M, Kubo M, Yamamoto K, Kitajima S, Kuroda E, Kawaguchi K, Sasaki T - J Nanopart Res (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555 Japan.

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/m(3), 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.

No MeSH data available.


Related in: MedlinePlus

Cell analysis and cytokine concentration in BALF following intratracheal instillation of nanoparticles. a Total cell count in BALF. b Neutrophil count in BALF. c Percentage of neutrophils in BALF. d Lymphocyte count in BALF. e Alveolar macrophage count in BALF. f LDH activity in BALF. g Concentration of CINC-1 in BALF. h Concentration of CINC-2 in BALF. i Concentration of HO-1 in BALF. Intratracheal instillation of CeO2 nanoparticles induced persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and HO-1 in BALF
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Fig3: Cell analysis and cytokine concentration in BALF following intratracheal instillation of nanoparticles. a Total cell count in BALF. b Neutrophil count in BALF. c Percentage of neutrophils in BALF. d Lymphocyte count in BALF. e Alveolar macrophage count in BALF. f LDH activity in BALF. g Concentration of CINC-1 in BALF. h Concentration of CINC-2 in BALF. i Concentration of HO-1 in BALF. Intratracheal instillation of CeO2 nanoparticles induced persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and HO-1 in BALF

Mentions: Figure 3 shows the cellular analysis of the BALF following the intratracheal instillation of CeO2 nanoparticles. In comparison with the negative control, the total cell count in BALF was significantly and persistently higher in the 1 mg group from 1 week to 3 months postexposure. The neutrophil counts and percentage in the BALF were also persistently and dose-dependently high in the 0.2 mg and the 1 mg groups. The macrophage and lymphocyte counts in the BALF were high in the 1 mg group at 1 week and 3 months and from 3 days to 3 months postexposure, respectively. A persistent increase in the released LDH activity was observed in the 0.2 and 1 mg groups. The peak level of LDH was at 3 days, and it returned to nearly the level of the negative control according to a time course, although there was a significant difference of value between the negative and the 1 mg groups until 6 months postexposure.Fig. 3


Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation.

Morimoto Y, Izumi H, Yoshiura Y, Tomonaga T, Oyabu T, Myojo T, Kawai K, Yatera K, Shimada M, Kubo M, Yamamoto K, Kitajima S, Kuroda E, Kawaguchi K, Sasaki T - J Nanopart Res (2015)

Cell analysis and cytokine concentration in BALF following intratracheal instillation of nanoparticles. a Total cell count in BALF. b Neutrophil count in BALF. c Percentage of neutrophils in BALF. d Lymphocyte count in BALF. e Alveolar macrophage count in BALF. f LDH activity in BALF. g Concentration of CINC-1 in BALF. h Concentration of CINC-2 in BALF. i Concentration of HO-1 in BALF. Intratracheal instillation of CeO2 nanoparticles induced persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and HO-1 in BALF
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644191&req=5

Fig3: Cell analysis and cytokine concentration in BALF following intratracheal instillation of nanoparticles. a Total cell count in BALF. b Neutrophil count in BALF. c Percentage of neutrophils in BALF. d Lymphocyte count in BALF. e Alveolar macrophage count in BALF. f LDH activity in BALF. g Concentration of CINC-1 in BALF. h Concentration of CINC-2 in BALF. i Concentration of HO-1 in BALF. Intratracheal instillation of CeO2 nanoparticles induced persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and HO-1 in BALF
Mentions: Figure 3 shows the cellular analysis of the BALF following the intratracheal instillation of CeO2 nanoparticles. In comparison with the negative control, the total cell count in BALF was significantly and persistently higher in the 1 mg group from 1 week to 3 months postexposure. The neutrophil counts and percentage in the BALF were also persistently and dose-dependently high in the 0.2 mg and the 1 mg groups. The macrophage and lymphocyte counts in the BALF were high in the 1 mg group at 1 week and 3 months and from 3 days to 3 months postexposure, respectively. A persistent increase in the released LDH activity was observed in the 0.2 and 1 mg groups. The peak level of LDH was at 3 days, and it returned to nearly the level of the negative control according to a time course, although there was a significant difference of value between the negative and the 1 mg groups until 6 months postexposure.Fig. 3

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555 Japan.

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/m(3), 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.

No MeSH data available.


Related in: MedlinePlus