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Response-metrics for acute lung inflammation pattern by cobalt-based nanoparticles.

Jeong J, Han Y, Poland CA, Cho WS - Part Fibre Toxicol (2015)

Bottom Line: The Co3O4 and CoO NPs showed about 11.46% and 92.65% solubility in ALF, respectively.Instillation of Co3O4 NPs produced neutrophilic inflammation, but CoO NPs induced eosinophilic inflammation.Instillation of CoCl2 showed a similar type and magnitude of inflammation as CoO NPs.

View Article: PubMed Central - PubMed

Affiliation: Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan-2dong, Saha-gu, Busan, 604-714, Republic of Korea. dudwlwjd@naver.com.

ABSTRACT

Background: Although the surface area metric has been proposed as a possible dose-metric for nanoparticles (NPs), it is limited to low-solubility NPs and the dose-metric for high-solubility NPs is poorly understood. In this study, we aimed to assess the appropriate dose-metric or response-metric for NPs using two cobalt (Co)-based NPs, cobalt monoxide (CoO) and cobalt oxide (Co3O4), which both show distinctive solubility, and determine the role of their soluble Co ions in inflammation.

Methods: We evaluated the physicochemical properties of NPs, including solubility in artificial lysosomal fluid (ALF, pH 5.5). Acute lung inflammogenicity was evaluated by bronchoalveolar lavage fluid analysis using the rat intratracheal instillation model. The appropriate response-metric was then determined by plotting several dose-metrics against parameters for lung inflammation. To investigate the effect of the soluble fraction of CoO NPs, the equivalent doses of Co ions from CoCl2 were instilled.

Results: The Co3O4 and CoO NPs showed about 11.46% and 92.65% solubility in ALF, respectively. Instillation of Co3O4 NPs produced neutrophilic inflammation, but CoO NPs induced eosinophilic inflammation. The number of eosinophils showed good correlation with the soluble Co ions dose from NPs (r2=0.987, p<0.001), while the number of neutrophils showed good correlation with the surface area dose of the biopersistent NPs (r2=0.876, p<0.001). Instillation of CoCl2 showed a similar type and magnitude of inflammation as CoO NPs.

Conclusions: In the Co-based NPs, the eosinophilic inflammation was produced by Co ions based on the ion metric, while the neutrophilic inflammation was developed based on the surface area metric of the biopersistent NPs.

No MeSH data available.


Related in: MedlinePlus

Correlation between the inflammatory parameters of nanoparticles (NPs) and dose-metrics including soluble Co ions, mass, surface area (SA), and SA dose of biopersistent NPs. Correlation between the number of eosinophils and (A) Co ions, (B) mass dose of NPs, (C) SA dose of NPs, or (D) SA dose of biopersistent NPs. Correlation between the number of neutrophils and (E) Co ions, (F) mass dose of NPs, (G) SA dose of NPs, or (H) SA dose of biopersistent NPs. When the dose–response curves of cobalt oxide (Co3O4) and cobalt monoxide (CoO) NPs were significantly different, separate curves were drawn with either linear regression or non-linear regression, while when the dose–response curves of each NP overlapped, the combined curves were prepared with best-fit regression models and the Pearson correlation test was applied. Values are mean ± SEM (n = 4) for each treatment group
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Fig3: Correlation between the inflammatory parameters of nanoparticles (NPs) and dose-metrics including soluble Co ions, mass, surface area (SA), and SA dose of biopersistent NPs. Correlation between the number of eosinophils and (A) Co ions, (B) mass dose of NPs, (C) SA dose of NPs, or (D) SA dose of biopersistent NPs. Correlation between the number of neutrophils and (E) Co ions, (F) mass dose of NPs, (G) SA dose of NPs, or (H) SA dose of biopersistent NPs. When the dose–response curves of cobalt oxide (Co3O4) and cobalt monoxide (CoO) NPs were significantly different, separate curves were drawn with either linear regression or non-linear regression, while when the dose–response curves of each NP overlapped, the combined curves were prepared with best-fit regression models and the Pearson correlation test was applied. Values are mean ± SEM (n = 4) for each treatment group

Mentions: To evaluate the best-fit dose–response curve, various dose-metrics, including mass, SA, fraction of soluble Co ions, and SA of biopersistent NPs, were plotted against the acute lung inflammatory parameters produced by Co3O4 and CoO treatment. When the number of eosinophils from each NP was plotted against mass, SA, or SA of biopersistent NPs, each NP showed a separate dose–response curve, while the dose–response curves from two NPs overlapped when they were plotted against soluble Co ions (r2 = 0.987, p < 0.001) (Fig. 3A-D). When the number of neutrophils from each NP was plotted against various dose-metrics, only the SA dose of biopersistent NPs showed good correlation (r2 = 0.876, p < 0.001), while other dose-metrics showed separate curves (Fig. 3E-H). In line with the dose–response curves of eosinophils, the dose–response curves of LDH and total protein from NPs overlapped when they were plotted against the soluble Co ion dose, while other dose-metrics showed separate curves (Fig. 4).Fig. 3


Response-metrics for acute lung inflammation pattern by cobalt-based nanoparticles.

Jeong J, Han Y, Poland CA, Cho WS - Part Fibre Toxicol (2015)

Correlation between the inflammatory parameters of nanoparticles (NPs) and dose-metrics including soluble Co ions, mass, surface area (SA), and SA dose of biopersistent NPs. Correlation between the number of eosinophils and (A) Co ions, (B) mass dose of NPs, (C) SA dose of NPs, or (D) SA dose of biopersistent NPs. Correlation between the number of neutrophils and (E) Co ions, (F) mass dose of NPs, (G) SA dose of NPs, or (H) SA dose of biopersistent NPs. When the dose–response curves of cobalt oxide (Co3O4) and cobalt monoxide (CoO) NPs were significantly different, separate curves were drawn with either linear regression or non-linear regression, while when the dose–response curves of each NP overlapped, the combined curves were prepared with best-fit regression models and the Pearson correlation test was applied. Values are mean ± SEM (n = 4) for each treatment group
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4440510&req=5

Fig3: Correlation between the inflammatory parameters of nanoparticles (NPs) and dose-metrics including soluble Co ions, mass, surface area (SA), and SA dose of biopersistent NPs. Correlation between the number of eosinophils and (A) Co ions, (B) mass dose of NPs, (C) SA dose of NPs, or (D) SA dose of biopersistent NPs. Correlation between the number of neutrophils and (E) Co ions, (F) mass dose of NPs, (G) SA dose of NPs, or (H) SA dose of biopersistent NPs. When the dose–response curves of cobalt oxide (Co3O4) and cobalt monoxide (CoO) NPs were significantly different, separate curves were drawn with either linear regression or non-linear regression, while when the dose–response curves of each NP overlapped, the combined curves were prepared with best-fit regression models and the Pearson correlation test was applied. Values are mean ± SEM (n = 4) for each treatment group
Mentions: To evaluate the best-fit dose–response curve, various dose-metrics, including mass, SA, fraction of soluble Co ions, and SA of biopersistent NPs, were plotted against the acute lung inflammatory parameters produced by Co3O4 and CoO treatment. When the number of eosinophils from each NP was plotted against mass, SA, or SA of biopersistent NPs, each NP showed a separate dose–response curve, while the dose–response curves from two NPs overlapped when they were plotted against soluble Co ions (r2 = 0.987, p < 0.001) (Fig. 3A-D). When the number of neutrophils from each NP was plotted against various dose-metrics, only the SA dose of biopersistent NPs showed good correlation (r2 = 0.876, p < 0.001), while other dose-metrics showed separate curves (Fig. 3E-H). In line with the dose–response curves of eosinophils, the dose–response curves of LDH and total protein from NPs overlapped when they were plotted against the soluble Co ion dose, while other dose-metrics showed separate curves (Fig. 4).Fig. 3

Bottom Line: The Co3O4 and CoO NPs showed about 11.46% and 92.65% solubility in ALF, respectively.Instillation of Co3O4 NPs produced neutrophilic inflammation, but CoO NPs induced eosinophilic inflammation.Instillation of CoCl2 showed a similar type and magnitude of inflammation as CoO NPs.

View Article: PubMed Central - PubMed

Affiliation: Lab of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, 840 Hadan-2dong, Saha-gu, Busan, 604-714, Republic of Korea. dudwlwjd@naver.com.

ABSTRACT

Background: Although the surface area metric has been proposed as a possible dose-metric for nanoparticles (NPs), it is limited to low-solubility NPs and the dose-metric for high-solubility NPs is poorly understood. In this study, we aimed to assess the appropriate dose-metric or response-metric for NPs using two cobalt (Co)-based NPs, cobalt monoxide (CoO) and cobalt oxide (Co3O4), which both show distinctive solubility, and determine the role of their soluble Co ions in inflammation.

Methods: We evaluated the physicochemical properties of NPs, including solubility in artificial lysosomal fluid (ALF, pH 5.5). Acute lung inflammogenicity was evaluated by bronchoalveolar lavage fluid analysis using the rat intratracheal instillation model. The appropriate response-metric was then determined by plotting several dose-metrics against parameters for lung inflammation. To investigate the effect of the soluble fraction of CoO NPs, the equivalent doses of Co ions from CoCl2 were instilled.

Results: The Co3O4 and CoO NPs showed about 11.46% and 92.65% solubility in ALF, respectively. Instillation of Co3O4 NPs produced neutrophilic inflammation, but CoO NPs induced eosinophilic inflammation. The number of eosinophils showed good correlation with the soluble Co ions dose from NPs (r2=0.987, p<0.001), while the number of neutrophils showed good correlation with the surface area dose of the biopersistent NPs (r2=0.876, p<0.001). Instillation of CoCl2 showed a similar type and magnitude of inflammation as CoO NPs.

Conclusions: In the Co-based NPs, the eosinophilic inflammation was produced by Co ions based on the ion metric, while the neutrophilic inflammation was developed based on the surface area metric of the biopersistent NPs.

No MeSH data available.


Related in: MedlinePlus