Redox analysis of antihyperuricemic agent and application to CKD/CVD treatment

• Project/Area Number: 24790160
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: KADOWAKI Daisuke 熊本大学, 薬学部, 准教授 (70433000)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 高尿酸血症 / ベンズブロマロン / 酸化ストレス / 抗酸化作用 / 高血圧 / アンジオテンシン

Outline of Final Research Achievements

Hyperuricemia, begins with induction of oxidative stress which closely related to the renin angiotensin system, is related to the onset and the progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Therefore, reduction of oxidative stress is important in hyperuricemia. In the present study, we evaluate the antioxidant effects of uricosuric agent benzbromarone. As a result, Benzbromarone has a direct radical scavenging activity against superoxide radicals and reduced oxidative stress induced by angiotensin II in the endothelial cell. Furthermore, benzbromarone exerts a direct antioxidant action in angiotensin II and salt induced-hypertension model rats. These results revealed that benzbromarone exerts a direct antioxidant action in the body. It is expected in the future that benzbromarone may be useful agent as a multiple antioxidants for the prevention of CVD and CKD.

Research Products

• [Journal Article] Direct Radical Scavenging Activity of Benzbromarone Provides Beneficial Antioxidant Properties for Hyperuricemia Treatment (2015)
  • Author(s): Kadowaki D, Sakaguchi S, Miyamoto Y, Taguchi K, Muraya N, Narita Y, Sato K, Chuang VT, Maruyama T, Otagiri M, Hirata S
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 3 Pages: 487-492
  • DOI: 10.1248/bpb.b14-00514
  • NAID: 130004872274
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] 尿酸と酸化ストレスの関連とベンズブロマロン，基礎から臨床へ (2012)
  • Author(s): 門脇 大介
  • Journal Title: 医薬の門 Volume: 52巻 Pages: 374-377
• [Journal Article] A uremic toxin, 3-carboxy-4-methyl-5-propyl-2-furanpropionate induces cell damage to proximal tubular cells via the generation of a radical intermediate. (2012)
  • Author(s): Yohei Miyamoto, Yasunori Katsumi Mera, Hiroshi Watanabe, Daisuke Kadowaki, Yu Ishima, Victor Tuan Giam Chuang, Keizo Sato, Masaki Otagiri, Toru Maruyama.
  • Journal Title: Biochemical Pharmacology Volume: 84 Issue: 9 Pages: 1207-1214
  • DOI: 10.1016/j.bcp.2012.07.033
  • Peer Reviewed
• [Presentation] Radical scavenging activity of benzbromarone as a novel property in vitro (2014)
  • Author(s): Daisuke Kadowaki, Shoichi Sakaguchi, Yohei Miyamoto, Nanako Muraya, Yuki Narita, Keizo Sato, Yu Ishima, Victor Chuang, Toru Maruyama, Masaki Otagiri, Sumio Hirata
  • Organizer: 5th FIP Pharmaceutical Sciences World Congress（PSWC2014）
  • Place of Presentation: Melbourne Convention and Exhibition Centre
  • Year and Date: 2014-04-12 – 2014-04-17
• [Presentation] 高血圧モデルラットの酸化ストレスに対するベンズブロマロンの効果 (2014)
  • Author(s): 村谷 菜々子，門脇 大介，北村 健一郎，成田 勇樹，丸山 徹，小田切 優樹，平田 純生
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本大学他（熊本県）
• [Presentation] 高血圧モデルラットの酸化ストレスに対するベンズブロマロンの効果 (2013)
  • Author(s): 村谷 菜々子，門脇 大介，北村 健一郎，成田 勇樹，丸山 徹，小田切 優樹，平田 純生
  • Organizer: 第23回日本医療薬学会年会
  • Place of Presentation: 東北大学他（宮城県）
• [Presentation] 高血圧モデルラットの酸化ストレスに対するベンズブロマロンの効果 (2013)
  • Author(s): 村谷 菜々子，門脇 大介，北村 健一郎，成田 勇樹，丸山 徹，小田切 優樹，平田 純生
  • Organizer: 第7回日本腎臓病薬物療法学会 学術集会・総会2013
  • Place of Presentation: 広島国際会議場（広島県）
• [Presentation] ベンズブロマロンの 抗酸化作用と血管内皮保護作用 (2012)
  • Author(s): 門脇 大介
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県）