Development of the evaluation system for cardiovascular effects of fiber materials

• Project/Area Number: 20H03935
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Jichi Medical University
• Principal Investigator: Sahoko Ichihara 自治医科大学, 医学部, 教授 (20378326)
• Co-Investigator(Kenkyū-buntansha): 三瀬 名丹 自治医科大学, 医学部, 准教授 (00360644) ; 池上 昭彦 自治医科大学, 医学部, 講師 (60748739) ; 市原 学 東京理科大学, 薬学部薬学科, 教授 (90252238)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: ナノ素材 / 炭素繊維 / 血管内皮細胞 / 動脈硬化 / 炎症反応 / 繊維状物質 / インフラマソーム / 酸化ストレス / 心血管系 / 初期影響評価マーカー

Outline of Research at the Start

ナノテクノロジーは、新材料創出、医療応用、地域温暖化防止に関係する環境技術等に応用可能であり、社会への貢献が期待される一方、新規工業的ナノ素材の健康への影響に社会的関心が高まり、生体影響に関するリスク評価が求められている。本研究では、今後その応用が期待されているカーボンナノチューブを含む繊維状物質に注目し、心血管系に対する影響を実験的に明らかにすると同時に、国内外のカーボンナノチューブ/炭素繊維加工工場の労働現場を調査し、曝露評価および繊維状物質によるヒトの心血管機能への影響を検討し、初期の影響を予測するバイオマーカーの有効性を検証する。

Outline of Final Research Achievements

In the present study, we focused on the health effects of fibrous materials containing carbon nanotubes, which are expected to be applied in the various fields. We experimentally investigated their effects on the cardiovascular system, and carried out work environment measurements at carbon fiber processing factory in Japan. As a result, high-concentration exposure to carbon nanotubes induced arteriosclerotic plaque formation in mice, suggesting that the inflammation induced by inflammasomes was involved as the mechanism. Moreover, factory survey confirmed that respirable fibers with high aspect ratios are generated during carbon fiber processing. In order to ensure the safety of the working environment, it is important to confirm the appropriate use of local exhaust ventilation and a risk assessment of carbon fiber debris generated after grinding of carbon fibers.

Academic Significance and Societal Importance of the Research Achievements

ナノテクノロジーは、新材料創出、医療応用、地域温暖化防止に関係する環境技術等に応用可能であり、社会への貢献が期待される。反面、新たな物性を持つため、ナノレベルの材料は従来の測定法では有害性の定量評価が出来ず、ヒトに対する未知の有害性リスクを有する可能性が懸念され、生体影響に関するリスク評価が求められている。本研究により、産業技術の発展や新しいイノベーションの創造に期待されるナノテクノロジーにおいて、重大なリスクを回避して有効利用を可能にするために、並行して、安全性評価の実施が必要であることが明らかになった。

Research Products

• [Int'l Joint Research] Mansoura Faculty of Medicine(エジプト)
• [Int'l Joint Research] Institute of Occupational Medicine(英国)
• [Int'l Joint Research] Universite de Paris(フランス)
• [Int'l Joint Research] Institute of Occupational Medicine(英国)
• [Int'l Joint Research] Universite de Paris(フランス)
• [Journal Article] In Vitro Exposure to Glucose Alters the Expression of Phosphorylated Proteins in Platelets (2023)
  • Author(s): Suzuki Mizuho、Takeshita Kyosuke、Kitamura Yuki、Kuribayashi Marie、Huang Zhenlie、Ichihara Gaku、Oikawa Shinji、Ichihara Sahoko
  • Journal Title: Biomedicines Volume: 11 Issue: 2 Pages: 543-543
  • DOI: 10.3390/biomedicines11020543
  • Peer Reviewed / Open Access
• [Journal Article] Carbonylated Proteins as Key Regulators in the Progression of Metabolic Syndrome (2023)
  • Author(s): Kitamura Yuki、Oikawa Shinji、Chang Jie、Mori Yurie、Ichihara Gaku、Ichihara Sahoko
  • Journal Title: Antioxidants Volume: 12 Issue: 4 Pages: 844-844
  • DOI: 10.3390/antiox12040844
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptome analysis of human cholangiocytes exposed to carcinogenic 1,2-dichloropropane in the presence of macrophages in vitro (2022)
  • Author(s): Abigail Ekuban, Shigeyuki Shichino, Cai Zong, Frederick Adams Ekuban, Kazuo Kinoshita, Sahoko Ichihara, Kouji Matsushima, Gaku Ichihara
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 1-14
  • DOI: 10.1038/s41598-022-15295-3
  • Peer Reviewed / Open Access
• [Journal Article] Factory site analysis of respirable fibers generated during the process of cutting and grinding of carbon fibers-reinforced plastics (2022)
  • Author(s): Kumoi Jun、Ikegami Akihiko、Fujitani Yuji、Morikawa Kota、Ichihara Gaku、Yano Takeo、Ichihara Sahoko
  • Journal Title: International Archives of Occupational and Environmental Health Volume: - Issue: 7 Pages: 1557-1565
  • DOI: 10.1007/s00420-022-01840-0
  • Peer Reviewed
• [Journal Article] Protective role of Nrf2 in zinc oxide nanoparticles-induced lung inflammation in female mice and sexual dimorphism in susceptibility (2022)
  • Author(s): Sehsah Radwa、Wu Wenting、Ichihara Sahoko、Hashimoto Naozumi、Zong Cai、Yamazaki Kyoka、Sato Harue、Itoh Ken、Yamamoto Masayuki、Elsayed Ahmed Ali、El-Bestar Soheir、Kamel Emily、Ichihara Gaku
  • Journal Title: Toxicology Letters Volume: 370 Pages: 24-34
  • DOI: 10.1016/j.toxlet.2022.09.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic ablation of Nrf2 exacerbates neurotoxic effects of acrylamide in mice (2021)
  • Author(s): Ekuban Frederick Adams、Zong Cai、Takikawa Madoka、Morikawa Kota、Sakurai Toshihiro、Ichihara Sahoko、Itoh Ken、Yamamoto Masayuki、Ohsako Seiichiroh、Ichihara Gaku
  • Journal Title: Toxicology Volume: 456 Pages: 152785-152785
  • DOI: 10.1016/j.tox.2021.152785
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro (2021)
  • Author(s): Ekuban Abigail、Zong Cai、Ekuban Frederick Adams、Kimura Yusuke、Takizawa Ryoya、Morikawa Kota、Kinoshita Kazuo、Ichihara Sahoko、Ohsako Seiichiroh、Ichihara Gaku
  • Journal Title: Toxics Volume: 9 Issue: 6 Pages: 128-128
  • DOI: 10.3390/toxics9060128
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 1,2-Dichloropropane induces γ-H2AX expression in human cholangiocytes only in the presence of macrophages (2021)
  • Author(s): Takizawa Ryoya、Ichihara Sahoko、Zong Cai、Kinoshita Kazuo、Sakurai Toshihiro、Ikegami Akihiko、Mise Nathan、Ichihara Gaku
  • Journal Title: Toxicology Letters Volume: 349 Pages: 134-144
  • DOI: 10.1016/j.toxlet.2021.06.009
  • Peer Reviewed
• [Journal Article] Effects of physiochemical characteristic of nano-sized TiO2 on the adhesion of monocytes to endothelial cells. (2020)
  • Author(s): 6.Suzuki Y, Ichihara G, Kawada S, Miyazawa K, Furutani T, Hayashida A, Watanabe E, Zong C, Tran L, Ikegami A, Ichihara S.
  • Journal Title: NanoImpac Volume: 20 Pages: 100257-100257
  • DOI: 10.1016/j.impact.2020.100257
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Proteomic analysis of liver proteins of mice exposed to 1,2-dichloropropane. (2020)
  • Author(s): Zhang X, Morikawa K, Mori Y, Zong C, Zhang L, Garner E, Huang C, Wu W, Chang J, Nagashima D, Sakurai T, Ichihara S, Oikawa S, Ichihara G.
  • Journal Title: Arch Toxicol. Volume: 94 Issue: 8 Pages: 2691-2705
  • DOI: 10.1007/s00204-020-02785-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functionalized surface-charge SiO2 nanoparticles induce pro-inflammatory responses, but are not lethal to Caco-2 cells. (2020)
  • Author(s): Tada-Oikawa S, Eguchi M, Yasuda MT, Izuoka K, Ikegami A, Vranic S, Boland S, Tran L, Ichihara G, Ichihara S
  • Journal Title: Chem Res Toxicol Volume: 印刷中 Issue: 5 Pages: 1226-1236
  • DOI: 10.1021/acs.chemrestox.9b00478
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Proteomic identification of the proteins related to cigarette smoke-induced cardiac hypertrophy in spontaneously hypertensive rats (2020)
  • Author(s): Kitamura Yuki、Mise Nathan、Mori Yurie、Suzuki Yuka、Ohashi Tomoki、Tada-Oikawa Saeko、Tokisu Masaki、Zong Cai、Oikawa Shinji、Ichihara Sahoko
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41598-020-75429-3
  • Peer Reviewed / Open Access
• [Presentation] 非晶質シリカナノ粒子による細胞傷害メカニズムの検討 (2023)
  • Author(s): 山崎京香, Sandra VRANIC, 渡邊英里, 宮川佳洋子, 竹内咲恵, 長田百合果, 市原佐保子, Wenting WU, Cai ZONG, 櫻井敏博, 佐藤聡, 原泰志, 寺島裕也, 松島綱治, 鈴木利宙, 安部良, Sonja Boland, Lang Tran, 市原学
  • Organizer: 第22回分子予防環境医学研究会
• [Presentation] 喫煙によりDNAメチル化が低下するゲノム領域のマウス相同領域におけるメチル化解析 (2023)
  • Author(s): 三瀬名丹、中杤 昌弘、松原 達昭、市原 学、横田 充弘、山本 健、市原 佐保子
  • Organizer: 第22回分子予防環境医学研究会
• [Presentation] Role of oxidative stress and caspase-8 in non-cell autonomous mechanisms of acrylamide-induced neurodegeneration (2023)
  • Author(s): Cai ZONG, Harue SATO, Benoit SCHNEIDER, Shigeyuki SHICHINO, Satoshi UEHA, Bin WU, Kouji MATSUSHIMA, Toshitugu OKAYAMA, Kazuho IKEO, Makoto URUSHITANI, Sho IWAMA, Alzahraa A. M FERGANY, Sahoko ICHIHARA, Seiichiroh OHSAKO, Gaku ICHIHARA
  • Organizer: 第22回分子予防環境医学研究会
• [Presentation] Deletion of IL-1beta enhances acrylamide-induced neurotoxicity in mice (2023)
  • Author(s): Alzahraa FERGANY, Cai ZONG, Frederick Adams EKUBAN, Aina SUZUKI, Bin WU, Satoshi UEHA, Kouji MATSUSHIMA, Sahoko ICHIHARA, Yoichiro IWAKURA ,Gaku ICHIHARA
  • Organizer: 第22回分子予防環境医学研究会
• [Presentation] 血中レジスチン濃度の人種横断型エピゲノムワイドメタ解析による (2023)
  • Author(s): 中杤昌弘、市原佐保子、山本 健、大中佳三、松原達昭、横田充弘
  • Organizer: 第22回分子予防環境医学研究会
• [Presentation] 喫煙によりDNAメチル化が低下するゲノム領域のマウス相同領域におけるメチル化解析 (2023)
  • Author(s): 三瀬名丹、中杤 昌弘、松原 達昭、市原 学、横田 充弘、山本 健、市原 佐保子
  • Organizer: 第93回日本衛生学会学術総会
• [Presentation] Respirable fibers generated from carbon fiber reinforced plastics (2022)
  • Author(s): Akihiko IKEGAMI, Jun KUMOI, Yuji FUJITANI, Kota MORIKAWA, Gaku ICHIHARA, Takeo YANO, Sahoko ICHIHARA
  • Organizer: The 30th Japan-China-Kirea Conference on Occupational Health
  • Int'l Joint Research
• [Presentation] ナノマテリアルと粒子の肺毒性 (2022)
  • Author(s): 市原 学, Radwa SEHSAH, Sandra VRANIC, Walaa ABDELNABY, Alzahraa FERGANY, 宗 才, 渡邊 英里, 佐藤 春恵, 山崎 京香, Sonja BOLAND, Lang TRAN, 市原 佐保子
  • Organizer: 第49回日本毒性学会学術年会
  • Invited
• [Presentation] Molecular mechanism of arsenic-induced hypertension: Inhibition of the vasoprotective axes of the renin-angiotensin system by arsenite (2022)
  • Author(s): Md. Shiblur RAHAMAN, Nathan MISE, Cai ZONG, Gaku ICHIHARA, Sahoko ICHIHARA
  • Organizer: 第49回日本毒性学会学術年会
• [Presentation] Impact of benzo[a]pyrene exposure on central nervous system of mice (2022)
  • Author(s): Walaa SH. ABD EL NABY, Alzahraa AM. FERGANY, Cai ZONG, Natsuko KUBOTA, Shinya YANAGIDA, Sahoko ICHIHARA, Gaku ICHIHARA
  • Organizer: 第49回日本毒性学会学術年会
• [Presentation] 酸化金属ナノマテリアルの心血管への影響 －産業衛生学の立場から－ (2022)
  • Author(s): 市原佐保子
  • Organizer: 第12回ナノカーボンバイオシンポジウム
  • Invited
• [Presentation] 血中レジスチン濃度の人種横断型エピゲノムワイドメタ解析による新規DNAメチル化サイトの同定 (2022)
  • Author(s): 中杤昌弘、市原佐保子、山本建、大中佳三、松原達昭、横田充弘
  • Organizer: 第67回日本人類遺伝学会大会
• [Presentation] ナノマテリアル曝露による肺への影響とその炎症誘導機構の検討 (2022)
  • Author(s): 滝澤亮哉、池上 昭、北村 祐貴、松本 和真、三瀬 名丹、市原 学、市原 佐保子
  • Organizer: 第22回分子予防環境医学研究会
• [Presentation] Debris from carbon fiber reinforced plastics (CFRP) in an occupational setting (2022)
  • Author(s): Akihiko Ikegami, Jun Kumoi, Yuji Fujitami, Gaku Ichihara, Takeo Yano, Sahoko Ichihara
  • Organizer: 33rd International Congress on Occupational Health (ICPH 2022)
  • Int'l Joint Research
• [Presentation] 炭素繊維強化プラスチック製造加工現場の繊維状物質 (2021)
  • Author(s): 雲井 純、池上 昭彦、藤谷 雄二、市原 学、矢野 竹男、市原 佐保子
  • Organizer: 第94回日本産業衛生学会
• [Presentation] Effect of Nrf2 deletion on inflammatory response in lung of female mice exposed to zinc oxide nanoparticles (2021)
  • Author(s): Sehsah R, Wu W, Ichihara S, Hashimoto N, Hasegawa Y, Zong C, Yamazaki K, Sato H, Itoh K, Yamamoto M, Ali Elsayed A, El-Bestar S, Kamel E, Ichihara G
  • Organizer: NanoTox2021
  • Int'l Joint Research
• [Presentation] Pulmonary effects of Fe3O4-PEG-PLGA nanoparticles in human bronchial epithelial cells and in wild type and Nrf2 knockout mice following pharyngeal aspiration (2021)
  • Author(s): Sato H, Zong C, Devineau S, McCord C, Ichihara S, Brookes O, Ekuban F, Itoh K, Yamamoto M, Boland S, Baeza-Squiban A, Ichihara G
  • Organizer: NanoTox2021
  • Int'l Joint Research
• [Presentation] Pulmonary effects of Fe3O4-PEG-PLGA nanoparticles in wild type and Nrf2 knockout mice following pharyngeal aspiration (2021)
  • Author(s): Sato H, Zong C, Devineau S, McCord C, Ichihara S, Brookes O, Ekuban F, Itoh K, Yamamoto M, Boland S, Baeza-Squiban A, Ichihara G
  • Organizer: 第48回日本毒性学会学術年会
• [Presentation] 炭素繊維強化プラスチック製造工場現場の微小粒子 (2021)
  • Author(s): 池上 昭彦、雲井 純、藤谷 雄二、矢野 竹男、市原 学、市原 佐保子
  • Organizer: 第48回産業中毒・生物学的モニタリング研究会
• [Presentation] Fe3O4-PEG-PLGA ナノ粒子の経気道曝露が肺にもたらす影響とNrf2 の役割 (2021)
  • Author(s): 佐藤春恵, 宗才, Stephanie Devineau, Claire McCord, 市原佐保子, Oliver Brookes, 伊東健, 山本雅之, Sonja Boland, Armelle Baeza-Squiban, 市原学
  • Organizer: フォーラム2021 衛生薬学・環境トキシコロジー
• [Presentation] Fe3O4-PEG-PLGA曝露によるヒト気管支上皮細胞と野生型および Nrf2欠損マウスの肺への影響 (2021)
  • Author(s): 佐藤 春恵、宗 才、Stephan ie Devineau, Claire McCord、市原 佐保子、Oliver Brookes、Frederick Adams Ekuban, 伊東 健、山本 雅之、Sonja Boland、Armelle Baeza Squiban、市原 学
  • Organizer: 第20回分子予防環境医学研究会
• [Presentation] Pulmonary effect of Fe3O4-PEG-PLGA nanoparticles in human bronchial epithalial cells and in wild type and Nrf2 knockout mice following pharyngeal aspiration. (2021)
  • Author(s): Harue Sato, Cai Zong, Stephan ie Devineau, Claire McCord, Sahoko Ichihara, Oliver Brookes, Ken Itoh, Masayuki Yamamoto, Sonja Boland, Armelle Baeza-Squiban, Gaku Ichihara
  • Organizer: Society of Toxicology 60th Annual Meeting (SOT2021)
  • Int'l Joint Research
• [Presentation] 炭素繊維強化プラスチックの製造加工現場で発生する微小粒子の個人曝露評価 (2020)
  • Author(s): 雲井純、池上昭彦、藤谷雄二、森川浩太、市原学、濱口隼人、矢野竹男、市原佐保子
  • Organizer: 第93回日本産業衛生学会
• [Presentation] Fe3O4-PEG-PLGA経気道曝露による野生型およびNrf2欠損マウスの肺への影響 (2020)
  • Author(s): 佐藤春恵、宗才、市原佐保子、伊東健、山本雅之、Sonja Boland、Armelle Baeza、市原学
  • Organizer: 第15回ナノ・バイオメディカル学会大会
• [Presentation] Pulmonary effect of exposure to Fe3O4-PEG-PLGA nanoparticles via pharyngeal aspiration in wild type and Nrf2 knockout mice. (2020)
  • Author(s): Harue Sato, Cai Zong, Sahoko Ichihara, Ken Itoh, Masayuki Yamamoto, Sonja Boland, Armelle Baeza-Squiban, Gaku Ichihara
  • Organizer: 9th NANO Conference
  • Int'l Joint Research
• [Presentation] Exposure assessment of debris from carbon fiber reinforced plastics in an occupational setting. (2020)
  • Author(s): Akihiko Ikegami, Jun Kumoi , Yuji Fujitani, Takeo Yano, Gaku Ichihara, Sahoko Ichihara
  • Organizer: 9th NANO Conference
  • Int'l Joint Research