Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies

Morimoto Yasuo, Hirohashi Masami, Ogami Akira, Oyabu Takako, Myojo Toshihiko, Nishi Ken-Ichiro, Kadoya Chikara, Todoroki Motoi, Yamamoto Makoto, Murakami Masahiro, Shimada Manabu, Wang Wei-Ning, Yamamoto Kazuhiro, Fujita Katsuhide, Endoh Shigehisa, Uchida Kunio, Shinohara Naohide, Nakanishi Junko, Tanaka Isamu

Description

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/m 3 ; 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. Results 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. Conclusion These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2010
• Nombre de lectures: 2
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

Morimoto et al . Particle and Fibre Toxicology 2010, 7 :4 http://www.particleandfibretoxicology.com/content/7/1/4

R E S E A R C H Open Access Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies Yasuo Morimoto 1* , Masami Hirohashi 1 , Akira Ogami 1 , Takako Oyabu 1 , Toshihiko Myojo 1 , Ken-ichiro Nishi 1 , Chikara Kadoya 1 , Motoi Todoroki 1 , Makoto Yamamoto 1 , Masahiro Murakami 1 , Manabu Shimada 2 , Wei-Ning Wang 2 , Kazuhiro Yamamoto 3 , Katsuhide Fujita 3 , Shigehisa Endoh 3 , Kunio Uchida 3 , Naohide Shinohara 3 , Junko Nakanishi 3 , Isamu Tanaka 1

Abstract Background: 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/m 3 ; 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. Results: 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,-2 ab 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,-2 ab and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2 ab and-3 in the fullerene group. Conclusion: These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

Background including energy device material, super conducting Nanomaterials are typically defined as structure compo- devices, magnets, and catalysts, and they can be mass- nents with at least one dimension less than 100 nm, and produced by a combustion method. Thus the demand possess superior characteristics that conventional mate- for fullerenes is expected to rise. It is unknown whether rials do not have, thus they are internationally and fullerenes cause lung injury or not and if so, what its aggressively researched and developed. Of the nanoma- mechanism is. One of the causes of this inconsistent terials, fullerene is a generic term for clusters consisting study result of industrial n anomaterials is the strong of many carbon atoms and a typical fullerene is C60 agglomerability of nanoparticles [2,3]. Nanoparticles that has a soccer-ball structure with 60 carbon atoms agglomerate by Van Der Waals forces and electrostatic [1]. Fullerenes have a mul titude of applications, effect soon after production in gaseous and liquid phases to become larger aggl omerates. It is expected eh-u.ac. that the formation of larger agglomerates may lead to 1 * In C st o i r t r u e t s e po of n I d n e d n u c s e t : ri y a a l s E u c o ol m o @ gi m ca e l d S .u ci o ences,U j n p iversityofOccupationaland the formation of bronchial and pulmonary artificial Environmental Health, Japan. Kitakyushu, Japan © 2010 Morimoto et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.