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Analysis of organ damage and oxidative stress caused by uremic toxins derived from the intestinal flora

Research Project

Project/Area Number 18K06774
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionSojo University

Principal Investigator

Kadowaki Daisuke  崇城大学, 薬学部, 教授 (70433000)

Co-Investigator(Kenkyū-buntansha) 瀬尾 量  崇城大学, 薬学部, 教授 (20435142)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords腸腎連関 / 尿毒症物質 / 慢性腎臓病 / ラクツロース / TMAO / 短鎖脂肪酸 / 合成二糖類 / 酸化ストレス / 腎障害 / 医薬品
Outline of Final Research Achievements

We studied the effect of lactulose on renal function in adenine-induced CKD rats and monitored uremic toxins and gut microbiota. As a result, lactulose groups improved sCr and BUN levels, and suppressed tubulointerstitial fibrosis, suggesting preventing of CKD progression by lactulose. Lac groups also lowered level of serum IS and proportions of gut microbiota producing IS precursor.

Academic Significance and Societal Importance of the Research Achievements

腸内細菌はヒトが分解できない物質を分解するが,その分解物の一部は吸収されて体内に入り血流を介して種々の臓器へ作用し,病気の発症や進展に悪影響を及ぼすことが明らかとなってきている。今回得られた結果は,腸内細菌の変化が尿毒症物質の体内への移行を減少させることで,腎臓病の悪化を抑制することが可能であることを示唆するものであり,今後の腎疾患に対する新規治療法への足掛かりとなる.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (33 results)

All 2021 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] Reduction-responsive and multi-drug deliverable albumin nanoparticles: an antitumor drug to Abraxane_ against human pancreatic tumor-bearing mice2021

    • Author(s)
      Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Victor Tuan Giam Chuang, Hidenori Ando, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri, Tatsuhiro Ishida
    • Journal Title

      ACS Applied Bio Materials

      Volume: 4,5 Pages: 4302-4309

    • DOI

      10.1016/j.lfs.2020.118991

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Cinacalcet on the Redox Status of Albumin in Secondary Hyperparathyroidism Patients Receiving Hemodialysis2020

    • Author(s)
      Imafuku Tadashi、Tanaka Motoko、Tokunaga Koki、Miyamura Shigeyuki、Kato Hiromasa、Tanaka Shoma、Nakano Takehiro、Hirata Kenshiro、Kadowaki Daisuke、Maeda Hitoshi、Matsushita Kazutaka、Otagiri Masaki、Komaba Hirotaka、Fukagawa Masafumi、Watanabe Hiroshi、Maruyama Toru
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 10 Pages: 1583-1590

    • DOI

      10.1248/bpb.b20-00472

    • NAID

      130007920876

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-10-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toxicological Property of Acetaminophen: The Dark Side of a Safe Antipyretic/Analgesic Drug?2020

    • Author(s)
      Ishitsuka Yoichi、Kondo Yuki、Kadowaki Daisuke
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 43 Issue: 2 Pages: 195-206

    • DOI

      10.1248/bpb.b19-00722

    • NAID

      130007793774

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2020-02-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of surface-deacetylated chitin nanofibers on non-alcoholic steatohepatitis model rats and their gut microbiota2020

    • Author(s)
      Goto Miwa、Iohara Daisuke、Michihara Akihiro、Ifuku Shinsuke、Azuma Kazuo、Kadowaki Daisuke、Maruyama Toru、Otagiri Masaki、Hirayama Fumitoshi、Anraku Makoto
    • Journal Title

      International Journal of Biological Macromolecules

      Volume: 164 Pages: 659-666

    • DOI

      10.1016/j.ijbiomac.2020.07.184

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of methods for more accurate estimation of kidney function in people with high muscle mass.2020

    • Author(s)
      Ichigi M, Nakatani S, Murakami M, Harada Y, Utsumi S, Ogata M, Maehara Y, Ikeda H, Shimada H, Fukunaga M, Narita Y, Saruwatari J, Kondo Y, Ishitsuka Y, Irie T, Kadowaki D, Hirata S.
    • Journal Title

      Clinical nephrology

      Volume: 94 Issue: 2 Pages: 86-96

    • DOI

      10.5414/cn110074

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo evaluation of drug dialyzability in a rat model of hemodialysis.2020

    • Author(s)
      Fukunaga M, Kadowaki D, Mori M, Hagiwara S, Narita Y, Saruwatari J, Tanaka R, Watanabe H, Yamasaki K, Taguchi K, Ito H, Maruyama T, Otagiri M, Hirata S.
    • Journal Title

      PLoS One

      Volume: 15 Issue: 6 Pages: 20-26

    • DOI

      10.1371/journal.pone.0233925

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative Study of Constipation Exacerbation by Potassium Binders Using a Loperamide-Induced Constipation Model2020

    • Author(s)
      Narita Yuki、Fukumoto Koichi、Fukunaga Masaki、Kondo Yuki、Ishitsuka Yoichi、Jono Hirofumi、Irie Tetsumi、Saito Hideyuki、Kadowaki Daisuke、Hirata Sumio
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 7 Pages: 2491-2491

    • DOI

      10.3390/ijms21072491

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coefficient of Determination between Estimated and Measured Renal Function in Japanese Patients with Sarcopenia May Be Improved by Adjusting for Muscle Mass and Sex: A Prospective Study2019

    • Author(s)
      Nakatani Sakura、Maeda Keisuke、Akagi Junji、Ichigi Misato、Murakami Marina、Harada Yoshihiko、Utsumi Sara、Fukunaga Masaki、Narita Yuki、Kondo Yuki、Ishitsuka Yoichi、Irie Tetsumi、Kadowaki Daisuke、Hirata Sumio
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 8 Pages: 1350-1357

    • DOI

      10.1248/bpb.b19-00154

    • NAID

      130007686738

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-08-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Processing grapefruit juice with γ‐cyclodextrin attenuates its inhibitory effect on cytochrome P450 3A activity2019

    • Author(s)
      Yamasaki Keishi、Iohara Daisuke、Oyama Yoko、Nishizaki Narumi、Kawazu Seitaro、Nishi Koji、Kadowaki Daisuke、Taguchi Kazuaki、Otagiri Masaki、Seo Hakaru
    • Journal Title

      Journal of Pharmacy and Pharmacology

      Volume: 72 Issue: 3 Pages: 356-363

    • DOI

      10.1111/jphp.13212

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity2019

    • Author(s)
      Narita Yuki、Hamamura Kana、Kashiyama Mami、Utsumi Sara、Kakizoe Yutaka、Kondo Yuki、Ishitsuka Yoichi、Jono Hirofumi、Irie Tetsumi、Mukoyama Masashi、Saito Hideyuki、Kadowaki Daisuke、Hirata Sumio、Kitamura Kenichiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 17 Pages: 4140-4140

    • DOI

      10.3390/ijms20174140

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats.2019

    • Author(s)
      Miyu Sueyoshi, Masaki Fukunaga, Mizue Mei, Atsushi Nakajima, Gaku Tanaka, Takayo Murase, Yuki Narita, Sumio Hirata & Daisuke Kadowaki
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 23 Issue: 7 Pages: 908-919

    • DOI

      10.1007/s10157-019-01727-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design and Evaluation of An Extended-Release Olmesartan Tablet Using Chitosan/Cyclodextrin Composites.2019

    • Author(s)
      Anraku, Makoto; Tabuchi, Ryo; Goto, Miwa; Iohara, Daisuke; Mizukai, Yasuyuki; Maezaki, Yuji; Michihara, Akihiro; Kadowaki, D; Otagiri, Masaki; Hirayama, Fumitoshi
    • Journal Title

      Pharmaceutics

      Volume: 11 Issue: 2 Pages: 82-82

    • DOI

      10.3390/pharmaceutics11020082

    • NAID

      120007018380

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Benzbromarone Attenuates Oxidative Stress in Angiotensin II- and Salt-Induced Hypertensive Model Rats2018

    • Author(s)
      Muraya Nanako、Kadowaki Daisuke、Miyamura Shigeyuki、Kitamura Kenichiro、Uchimura Kohei、Narita Yuki、Miyamoto Yohei、Chuang Victor Tuan Giam、Taguchi Kazuaki、Maruyama Toru、Otagiri Masaki、Hirata Sumio
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2018 Issue: 1 Pages: 1-8

    • DOI

      10.1155/2018/7635274

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A simple formula for predicting drug removal rates during hemodialysis2018

    • Author(s)
      Urata M, Narita Y, Fukunaga M, Kadowaki D, Hirata S
    • Journal Title

      Ther Apher Dial

      Volume: in print Issue: 5 Pages: 485-493

    • DOI

      10.1111/1744-9987.12675

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ノイロトロピンの抗酸化作用及びHIF1αを介した腎保護効果2020

    • Author(s)
      門脇大介, 福永雅樹 ,内田朱美, 末吉美優, 前田仁志 ,成田勇樹, 渡邊 博志, 丸山徹, 平田純生 ,瀬尾量
    • Organizer
      日本薬剤学会第35年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 腸腎連関をターゲットとしたラクツロースの腎不全に対する効果2020

    • Author(s)
      末吉美優, 福永雅樹 ,中島 淳志 ,田中雅久, 村瀬貴代 ,成田勇樹 ,平田純生, 前田仁志 ,渡邊博志 ,瀬尾量, 丸山徹, 門脇大介
    • Organizer
      日本薬剤学会第35年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 前立腺全摘出術後の鎮痛薬が術後腎機能に与える影響-傾向スコアマッチングを用いた解析-2020

    • Author(s)
      西村文宏, 牛島智子, 原一正, 門脇大介, 宮村重幸, 鬼木健太郎, 猿渡淳二
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ノイロトロピンの多面的な作用の解明と腎疾患への応用2020

    • Author(s)
      門脇大介, 福永雅樹 ,内田朱美, 末吉美優, 前田仁志, 成田勇樹, 渡邊 博志, 丸山徹, 瀬尾量, 平田純生
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] オンコネフロロジー概論2020

    • Author(s)
      門脇大介
    • Organizer
      第14回日本腎臓病薬物療法学会学術集会・総会2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Renal Protective Effect of Lactulose Targeting of Gut-Kidney Axis2019

    • Author(s)
      Miyu Sueyoshi, Masaki Fukunaga, Mizue Mei, Atsushi Nakajima, Gaku Tanaka, Takayo Murase, Yuki Narita, Sumio Hirata, Daisuke Kadowaki
    • Organizer
      ISN/WCN 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Accumulation of acetaminophen metabolites exerts kidney protective effect in renal failure rat model.2019

    • Author(s)
      Daisuke Kadowaki, Masaki Fukunaga, Miyu Sueyoshi, Kohei Uchimura, Kenichiro Kitamura, Yuki Narita, Toru Maruyama, Masaki Otagiri, Hakaru Seo, Sumio Hirata
    • Organizer
      ISN/WCN 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ノイロトロピンの抗酸化作用の解析2019

    • Author(s)
      内田朱美, 福永雅樹, 原岡なつみ, 成田勇樹, 丸山徹, 平田純生, 瀬尾量, 門脇大介
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] トロンボモデュリンαの抗酸化の解析と尿毒症物質に対する保護効果の検討2019

    • Author(s)
      馬場汐里, 松山留巳, 福永雅樹, 末吉美優, 成田勇樹, 丸山徹, 平田純生, 瀬尾量, 門脇大介
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] ラクツロースの腸内環境および腎不全に対する効果2019

    • Author(s)
      末吉美優, 門脇大介, 福永雅樹, 中島淳志, 田中雅久, 村瀬貴代, 成田勇樹, 平田純生, 丸山徹
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 5/6腎摘ラットを用いたノイロトロピンの腎保護効果の検討2019

    • Author(s)
      福永雅樹, 門脇大介, 末吉美優, 内田朱美, 成田勇樹, 丸山徹, 瀬尾量, 平田純生
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腎疾患治療への応用を目指したカモスタットの抗酸化作用解析2019

    • Author(s)
      樫山真美, 成田勇樹, 浜村佳奈, 柿添豊, 向山政志, 門脇大介, 平田純生, 北村健一郎
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 血液透析による薬物除去率の予測式の構築2019

    • Author(s)
      村上鞠奈, 浦田元樹, 近藤悠希, 成田勇樹, 門脇大介, 平田純生
    • Organizer
      第64回日本透析医学会学術集会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] The antioxidant activity of neurotropin contributes to the kidney protective effect2019

    • Author(s)
      Masaki Fukunaga, Akemi Uchida, Miyu Sueyoshi, Hitoshi Maeda, Yuki Narita, Hiroshi Watanabe, Toru Maruyama, Hakaru Seo, Sumio Hirata, Daisuke Kadowaki
    • Organizer
      ASN KIDNEY WEEK 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 医薬品の抗酸化作用解析を基盤とした腎疾患治療への応用2019

    • Author(s)
      門脇大介
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 末吉美優,門脇大介,福永雅樹,中島淳志,田中雅久,村瀬貴代,成田勇樹,平田純生 丸山徹2019

    • Author(s)
      ラクツロースの腸内環境および腎不全に対する効果
    • Organizer
      第62回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Renal Protective Effect of Lactulose Targeting of Gut-Kidney Axis2019

    • Author(s)
      Miyu Sueyoshi, Masaki Fukunaga, Mizue Mei, Atsushi Nakajima, Gaku Tanaka, Takayo Murase, Yuki Narita, Sumio Hirata, Daisuke Kadowaki
    • Organizer
      国際腎臓学会・世界腎臓学会議(ISN WCN 2019)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ストレプトゾトシン誘発早期糖尿病モデルラットを用いたラクツロースの血糖値および腎機能に及ぼす影響2018

    • Author(s)
      末吉美優,福永雅樹,目井瑞会,成田勇樹,平田純生,門脇大介
    • Organizer
      第61回日本腎臓学会学術総会(新潟)
    • Related Report
      2018 Research-status Report
  • [Presentation] 酸化ストレスの観点から考える老年薬学2018

    • Author(s)
      門脇大介
    • Organizer
      医療薬学フォーラム2018・第26回クリニカルファーマシーシンポジウム(
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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