Studies on modifying factors for arsenic toxicity in arsenic-endemic areas in Asia

• Project/Area Number: 24406009
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Environmental pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: HIMENO Seiichiro 徳島文理大学, 薬学部, 教授 (20181117)
• Co-Investigator(Kenkyū-buntansha): SUMI Daigo 徳島文理大学, 薬学部, 准教授 (30400683) ; MIYATAKA Hideki 徳島文理大学, 薬学部, 助教 (50157658)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: ヒ素 / アジア / 地下水汚染 / 免疫能力 / ヒ素解毒能力 / バングラデシュ / カンボジア / 地下水 / 動脈硬化 / メチル化代謝 / 免疫能

Outline of Final Research Achievements

Health hazards caused by arsenic pollution of tube-well water are endemic in Asian countries. We have collected the samples of hair, nail, blood, urine, and drinking water from Bangladesh and Cambodian residents to assess the dose-response relationship between the levels of arsenic exposure and health effects. In Bangladesh, we found that elevating levels of arsenic exposure were well correlated with biochemical indicators for hepatotoxicity, atherosclerosis, and hypertension. In Cambodia, the contribution of tube-well water as well as the consumption of fish and rice to arsenic exposure was investigated. Chemical forms of arsenic in freshwater fish in Cambodia were precisely evaluated. In a cell culture system, we found that alternative splicing of the gene for arsenic methylation (detoxifying) enzyme could be a cause for individual difference in sensitivity to arsenic toxicity. Also, we found that arsenic exposure reduces the ability of natural killer cells for killing tumor cells.

Research Products

• [Journal Article] High accumulation of arsenic in the esophagus of mice after exposure to arsenite. (2015)
  • Author(s): Sumi, D., Tsurumoto, M., Yoshino, Y., Inoue, M., Yokobori, T., Kuwano, H., Himeno, S.
  • Journal Title: Arch. Toxicol. Volume: 89 Issue: 10 Pages: 1751-1758
  • DOI: 10.1007/s00204-014-1326-3
  • Peer Reviewed
• [Journal Article] Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh. (2014)
  • Author(s): Huda, N., Hossain, S., Rahman, M., Karim, M. R., Islam, K., Mamun, A. A., Hossain, M. I., Mohanto, N. C., Alam, S., Aktar, S., Arefin, A., Ali, N., Salam, K. A., Aziz, A., Saud, Z. A., Miyataka, H., Himeno, S., Hossain, K.
  • Journal Title: Toxicol. Appl. Pharmacol. Volume: 281 Issue: 1 Pages: 11-18
  • DOI: 10.1016/j.taap.2014.09.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Associations of total arsenic in drinking water, hair and nails with serum vascular endothelial growth factor in arsenic-endemic individuals in Bangladesh. (2014)
  • Author(s): Rahman, M., Al Mamun, A., Karim, R., Islam, K., Al Amin, H., Hossain, S., Hossain, I., Alam Saud, Z., Noman, A. S., Miyataka, H., Himeno, S., Hossain, K.
  • Journal Title: Chemosphere Volume: 120C Pages: 336-342
  • DOI: 10.1016/j.chemosphere.2014.08.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An Integrative Study of the Genetic, Social and Environmental Determinants of Chronic Kidney Disease Characterized by Tubulointerstitial Damages in the North Central Region of Sri Lanka (2014)
  • Author(s): Nanayakkara, S., Senevirathna, S., Abeysekera, T., Chandrajith, R., Ratnatunga, N., Gunarathne, E., Yan, J., Hitomi, T., Muso, E., Komiya, T., Harada, K., Liu, W., Kobayashi, H., Okuda, H., Sawatari, H., Matsuda, F., Yamada, R., Watanabe, T., Miyataka, H., Himeno, S., Koizumi, A.
  • Journal Title: Journal of Occupational Health Volume: 56 Issue: 1 Pages: 28-38
  • DOI: 10.1539/joh.13-0172-OA
  • NAID: 130004848049
  • ISSN: 1341-9145, 1348-9585
  • Peer Reviewed
• [Journal Article] Arsenite retards the cardiac differentiation of rat cardiac myoblast H9c2 cells.Biochem. (2013)
  • Author(s): Sumi, D., Abe, K., Himeno, S.
  • Journal Title: Biophys. Res. Commun. Volume: (in press) Issue: 2 Pages: 175-179
  • DOI: 10.1016/j.bbrc.2013.05.069
  • Peer Reviewed
• [Journal Article] Increases in oxidized low density lipoprotein and other inflammatory and adhesion molecules with a concomitant decrease in high density lipoprotein in the individuals exposed to arsenic in Bangladesh. (2013)
  • Author(s): Karim, M. R., Rahman, M., Islam, K., Mamun, A. A., Hossain, H., Hossain, E., Aziz, A., Yeasmin, F., Agarwal, S., Saud, Z. A., Nikkon, F., Hossain, M., Mandal, A., Jenkins, R. O., Haris, P. I., Miyataka, H., Himeno, S., and Hossain, K.
  • Journal Title: Toxicol. Sci. Volume: 135(1) Issue: 1 Pages: 17-25
  • DOI: 10.1093/toxsci/kft130
  • Peer Reviewed
• [Journal Article] Involvement of Nrf2 activation in the upregulation of S100A9 by exposure to inorganic arsenite. (2013)
  • Author(s): Sumi, D., Shimizu Y., Himeno S.
  • Journal Title: Int. J. Mol. Med. Volume: 31(1) Issue: 1 Pages: 259-264
  • DOI: 10.3892/ijmm.2012.1185
  • Peer Reviewed
• [Presentation] バングラデシュのヒ素汚染地域における血管障害． (2014)
  • Author(s): 姫野誠一郎、宮高透喜．
  • Organizer: 第20回ヒ素シンポジウム．
  • Place of Presentation: 千葉
  • Year and Date: 2014-12-06
• [Presentation] メコン川流域ヒ素汚染地域の魚介類のヒ素濃度と住民の尿中ヒ素濃度. (2014)
  • Author(s): 姫野誠一郎、藤森千鶴、宮高透喜.
  • Organizer: 第84回日本衛生学会学術総会
  • Place of Presentation: 岡山
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] Effects of inorganic arsenite on the function of transcription factor Evi-1. (2013)
  • Author(s): ○田村嶺、角大悟、姫野誠一郎
  • Organizer: 第23回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 武蔵野大学（東京）
• [Presentation] Effects of arsenite on esophagus in acutely and chronically administrated mice. (2013)
  • Author(s): ○鶴本未有、角大悟、姫野誠一郎
  • Organizer: 第23回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 武蔵野大学（東京）
• [Presentation] Speciation of urinary arsenic metabolites in Cambodian residents living in arsenic-polluted areas. (2013)
  • Author(s): ○姫野誠一郎、宮高透喜、森田晴絵、S.Sthiannopkao
  • Organizer: Metallomics 2013
  • Place of Presentation: Oviedo (Spain)
• [Presentation] カンボジアヒ素汚染地域における尿中ヒ素化学形態と魚介類摂取量. (2013)
  • Author(s): ○姫野誠一郎、森田晴絵、藤森千鶴、宮高透喜、Suthipong Sthiannopkao
  • Organizer: 第19回ヒ素シンポジウム
  • Place of Presentation: 九州大学（博多市）
• [Presentation] Effects of arsenic on immunological functions. (2013)
  • Author(s): ○角大悟、姫野誠一郎
  • Organizer: Xth ISTERH 2013
  • Place of Presentation: 京王プラザホテル（東京）
  • Invited
• [Presentation] Metal profiles in segmented hair samples obtained in arsenic-polluted areas. (2013)
  • Author(s): ○Yuan-Po Lee、宮高透喜、姫野誠一郎
  • Organizer: Xth ISTERH 2013
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] Associations of circulating molecules involved in atherosclerosis with arsenic exposure. (2013)
  • Author(s): ○Rezaul Karim、Mashiur Rahman、Khairul Islam、Abdullah Al Mamun、姫野誠一郎、Khaled Hossain
  • Organizer: Xth ISTERH 2013
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] Assessing Arsenic Exposure by Human Samples in the Residents of Cambodia. (2013)
  • Author(s): ○姫野誠一郎
  • Organizer: NIES Arsenic Workshop 2013
  • Place of Presentation: 国立環境研究所（つくば市）
  • Invited
• [Presentation] ヒ素化合物による免疫担当細胞の機能障害 (2013)
  • Author(s): 角大悟、津山博匡、原田久美、山近杏奈、小川智子、姫野誠一郎
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜(招待講演)
• [Presentation] Relationship between biochemical indicators and arsenic exposure among people drinking tube-well water in Bangladesh (2012)
  • Author(s): 姫野誠一郎
  • Organizer: 第22回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 金沢
• [Presentation] Reduction of the degranulation in rat RBL-2H3 mast cells by chronic exposure to arsenite via impairment of store-operated Ca2+ entry (2012)
  • Author(s): 角大悟、清水由里、姫野誠一郎
  • Organizer: The 6th International Congress of Asian Society of Toxicology
  • Place of Presentation: 仙台
• [Presentation] 亜ヒ酸のNK細胞活性化に対する免疫毒性作用 (2012)
  • Author(s): 角大悟、原田久美、小川智子、津山博匡、姫野誠一郎
  • Organizer: 第39回日本毒性学会学術年会
  • Place of Presentation: 仙台
• [Presentation] 亜ヒ酸曝露によるNK細胞活性化に対する影響 (2012)
  • Author(s): 原田久美、小川智子、角大悟、姫野誠一郎
  • Organizer: 第3回メタロミクス研究フォーラム
  • Place of Presentation: 東京
• [Presentation] Jurkat細胞が分泌するサイトカインに対する亜ヒ酸の影響 (2012)
  • Author(s): 山近杏奈、角大悟、姫野誠一郎
  • Organizer: 第3回メタロミクス研究フォーラム
  • Place of Presentation: 東京
• [Presentation] ATPシグナル伝達に対する亜ヒ酸の影響 (2012)
  • Author(s): 角大悟、岡田秀太、與儀邦子、宮高透喜、姫野誠一郎
  • Organizer: 第19回日本免疫毒性学会学術大会
  • Place of Presentation: 東京
• [Presentation] 亜ヒ酸がマスト細胞の応答性と遺伝子発現に及ぼす影響 (2012)
  • Author(s): 姫野誠一郎、清水由里、角大悟
  • Organizer: 第18回ヒ素シンポジウム
  • Place of Presentation: 宮崎
• [Remarks] 徳島文理大学薬学部衛生化学・研究業績
  • URL: http://p.bunri-u.ac.jp/lab10/gyoseki.html