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Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

Tada Y, Yano N, Takahashi H, Yuzawa K, Ando H, Kubo Y, Nagasawa A, Inomata A, Ogata A, Nakae D - J Toxicol Pathol (2013)

Bottom Line: Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group.The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung.These responses occur in a dose-dependent manner without apparent differences among sexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku, Tokyo 169-0073, Japan.

ABSTRACT
Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

No MeSH data available.


Related in: MedlinePlus

Representative gross views (upper row) and cross-sections of the formalin-fixed tissues (lower row) of the lungs. The doses of magnetite were 0 (control) (A), 0.2 (B), 1.0 (C) and 5.0 (D) mg/kg body weight per administration.
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fig_003: Representative gross views (upper row) and cross-sections of the formalin-fixed tissues (lower row) of the lungs. The doses of magnetite were 0 (control) (A), 0.2 (B), 1.0 (C) and 5.0 (D) mg/kg body weight per administration.

Mentions: An apparent macroscopic finding was obtained at necropsy in the high-dose groups of both sexes, with the lungs being slightly enlarged in association with dark brown patches scattered in almost all their lobes (Fig. 3Fig. 3.


Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

Tada Y, Yano N, Takahashi H, Yuzawa K, Ando H, Kubo Y, Nagasawa A, Inomata A, Ogata A, Nakae D - J Toxicol Pathol (2013)

Representative gross views (upper row) and cross-sections of the formalin-fixed tissues (lower row) of the lungs. The doses of magnetite were 0 (control) (A), 0.2 (B), 1.0 (C) and 5.0 (D) mg/kg body weight per administration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921922&req=5

fig_003: Representative gross views (upper row) and cross-sections of the formalin-fixed tissues (lower row) of the lungs. The doses of magnetite were 0 (control) (A), 0.2 (B), 1.0 (C) and 5.0 (D) mg/kg body weight per administration.
Mentions: An apparent macroscopic finding was obtained at necropsy in the high-dose groups of both sexes, with the lungs being slightly enlarged in association with dark brown patches scattered in almost all their lobes (Fig. 3Fig. 3.

Bottom Line: Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group.The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung.These responses occur in a dose-dependent manner without apparent differences among sexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku, Tokyo 169-0073, Japan.

ABSTRACT
Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

No MeSH data available.


Related in: MedlinePlus