Novel antioxidant therapy for radiation-induced injuries

• Project/Area Number: 26670569
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Defense Medical College
• Principal Investigator: Kinoshita Manabu 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 免疫・微生物学, 准教授 (70531391)
• Co-Investigator(Kenkyū-buntansha): 異島 優 徳島大学, 大学院医歯薬学研究部(薬学系), 准教授 (00457590) ; 山本 哲生 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 防衛医学, 講師 (20647979) ; 加地 辰美 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 放射線医学, 教授 (50148110) ; 関 修司 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 免疫・微生物学, 教授 (80531392)
• Co-Investigator(Renkei-kenkyūsha): Maruyama Toru 熊本大学, 薬学部, 教授 (90423657)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 放射線防護剤 / ビタミンC / 糖転移ビタミンC / 抗酸化アルブミン / 糖転移へスぺリジン / 放射線治療 / ヘスペリジン / 全身被ばく / 放射線 / ビタミンＣ / 被曝後投与 / 放射線防護材

Outline of Final Research Achievements

We studied vitamin C as a radioprotective agent, focusing on its antioxidative effect. We examined the effect of post-exposure treatment with intraperitoneal administration of vitamin C on radiation-induced bone marrow dysfunction in mice. Administration with high-dose vitamin C, even at 24 h after whole-body irradiation, was still effective in avoiding bone marrow dysfunction, thereby increasing mouse survival after radiation. Ascorbic acid 2-glucoside (AA2G) is a stabilized derivative of vitamin C and rapidly hydrolysed into vitamin C and glucose in the hosts. We examined the effect of AA2G treatment during pelvic radiotherapy against bladder tumors in tumor-bearing rats. AA2G treatment during the pelvic radiotherapy improved radiation-induced intestinal damage without reducing antitumor effect of pelvic radiotherapy. Vitamin C as well as AA2G may be useful for patients receiving not only accidental radiation exposure but also scheduled radiotherapy against neoplasms.

Research Products

• [Journal Article] In vivo LPS tolerance recruits CD11b+ macrophages to the liver with enhanced bactericidal activity and low TNF-releasing capability, resulting in drastic resistance to lethal septicemia. (2017)
  • Author(s): Kinoshita M, Miyazaki H, Nakashima, H, Nakashima M, Nishikawa M, Ishikiriyama T, Kato S, Iwaya K, Hiroi S, Shinomiya N, Seki S.
  • Journal Title: J. Innate Immun. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Apoptosis induction of Poly-S-nitrosated human serum albumin in resistant solid tumor under hypoxia can be restored by phosphodiesterase 5 inhibition (2017)
  • Author(s): Ikeda M, Ishima Y, Chuang VTG, Ikeda T, Kinoshita R, Watanabe H, Ishida T, Otagiri M, Maruyama T
  • Journal Title: Nitric Oxide Volume: S1089-8603 Pages: 30269-5
  • DOI: 10.1016/j.niox.2017.04.005
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach (2017)
  • Author(s): Ikeda M, Ishima Y, Shibata A, Chuang VTG, Sawa T, Ihara H, Watanabe H, Xian M, Ouchi Y, Shimizu T, Ando H, Ukawa M, Ishida T, Akaike T, Otagiri M, Maruyama T
  • Journal Title: Anal Chim Acta Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Human Serum Albumin as Carrier in Drug Delivery Systems (2016)
  • Author(s): 10.Ishima Y, Maruyama T
  • Journal Title: YAKUGAKU ZASSHI Volume: 136 Issue: 1 Pages: 39-47
  • DOI: 10.1248/yakushi.15-00227-1
  • NAID: 130005115184
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2016-01-01
  • Peer Reviewed / Open Access
• [Journal Article] Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease (2016)
  • Author(s): Shibata A, Ishima Y, Ikeda M, Sato H, Imafuku T, Chuang VT, Ouchi Y, Abe T, Watanabe H, Ishida T, Otagiri M, Maruyama T
  • Journal Title: Biochem Biophys Res Commun Volume: 479 Issue: 3 Pages: 578-583
  • DOI: 10.1016/j.bbrc.2016.09.113
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations (2016)
  • Author(s): Miyamura S, Imafuku T, Anraku M, Taguchi K, Yamasaki K, Tominaga Y, Maeda H, Ishima Y, Watanabe H, Otagiri M, Maruyama T
  • Journal Title: J Pharm Sci. Volume: 105 Issue: 3 Pages: 1043-1049
  • DOI: 10.1016/j.xphs.2015.12.015
  • Peer Reviewed
• [Journal Article] Treatment of irradiated mice with high-dose ascorbic acid reduced lethality. (2015)
  • Author(s): Sato T, Kinoshita M, Yamamoto T, Ito M, Nishida T, Takeuchi M, Saitoh D, Seki S, Mukai Y.
  • Journal Title: PLoS ONE Volume: 10 Issue: 2 Pages: e0117020-e0117020
  • DOI: 10.1371/journal.pone.0117020
  • Peer Reviewed / Open Access
• [Journal Article] Polythiol-containing, recombinant mannosylated-albumin is a superior CD68+/CD206+ Kupffer cell-targeted nano-antioxidant for the treatment of two acute hepatitis models. (2015)
  • Author(s): Maeda H, Hirata K, Watanabe H, Ishima Y, Chuang VT, Taguchi K, Inatsu A, Kinoshita M, Tanaka M, Sasaki Y, Otagiri M, Maruyama T.
  • Journal Title: J Pharmacol Exp Ther Volume: 352 Issue: 2 Pages: 244-257
  • DOI: 10.1124/jpet.114.219493
  • Peer Reviewed / Open Access
• [Journal Article] Photodynamic therapy mediates innate immune responses via fibroblast-macrophage interactions. (2015)
  • Author(s): 4.Zulaziz N, Azhim A, Himeno N, Tanaka M, Satoh Y, Kinoshita M, Miyazaki H, Saitoh D, Shinomiya N, Morimoto Y.
  • Journal Title: Hum. Cell Volume: 28 Issue: 4 Pages: 159-166
  • DOI: 10.1007/s13577-015-0118-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ビタミンCによる放射線傷害軽減化対策ーより安全で使いやすい防護剤の開発ー (2015)
  • Author(s): 木下学、山本哲生、伊藤靖利、佐藤智人
  • Journal Title: Isotope News Volume: 739 Pages: 2-8
• [Journal Article] Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury. (2014)
  • Author(s): Sato A, Nakashima H, Nakashima M, Ikarashi M, Nishiyama K, Kinoshita M, Seki S
  • Journal Title: PLoS ONE Volume: 9 Issue: 3 Pages: e92515-e92515
  • DOI: 10.1371/journal.pone.0092515
  • Peer Reviewed / Open Access
• [Journal Article] A combination of pre- and post-exposure ascorbic acid rescues mice from radiation-induced lethal gastrointestinal damage. (2014)
  • Author(s): Ito Y, Kinoshita M, Yamamoto T, Sato T, Obara T, Saitoh D, Seki S, Takahashi Y.
  • Journal Title: Int. J. Mol. Sci. Volume: 14 Issue: 10 Pages: 19618-35
  • DOI: 10.3390/ijms141019618
  • Peer Reviewed / Open Access
• [Journal Article] 放射線被曝時のIntestinal Failureとその対策 (2014)
  • Author(s): 木下学
  • Journal Title: 消化と吸収 Volume: 36 Pages: 341-347
• [Presentation] 外科侵襲後の複合免疫不全とその対策 (2015)
  • Author(s): 木下学
  • Organizer: 第30回日本ショック学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-22
  • Invited
• [Presentation] 放射線防護剤としての新規安定型ビタミンＣ製剤の開発 (2015)
  • Author(s): 木下学
  • Organizer: 日本集団災害医学会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-17
• [Book] Vitamin C (2017)
  • Author(s): Yamamoto T, Kinoshita M
  • Total Pages: 25
  • Publisher: INTEC