Topical Application of Nitrosonifedipine, a Novel Radical Scavenger, Ameliorates Ischemic Skin Flap Necrosis in a Mouse Model

• Project/Area Number: 16K20360
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Plastic surgery
• Research Institution: National Cancer Center Japan (2017-2018); The University of Tokushima (2016)
• Principal Investigator: Fukunaga Yutaka 国立研究開発法人国立がん研究センター, 東病院, 医員 (50748069)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 皮弁壊死 / ニトロソニフェジピン / 酸化ストレス / 抗酸化剤

Outline of Final Research Achievements

Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. We evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyse oxidative stress, apoptosis and endothelial dysfunction. We demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis.

Academic Significance and Societal Importance of the Research Achievements

現時点では皮弁壊死予防のために血流を改善する目的でプロスタグランディン製剤や抗凝固剤などが使用されているが、これらとは違った作用機序の薬剤を開発することで多面的に皮弁壊死に対してアプローチすることができ、合併症発生頻度減少、重症度軽減につながることが期待される。今回の研究により皮弁壊死を予防する新たな薬剤としてニトロソニフェジピンが有効である可能性を示した。

Research Products

• [Journal Article] Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model. (2017)
  • Author(s): Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yuya Horinouchi, Eriko Sairyo, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Yoshiro Abe, Ichiro Hashimoto, Toshiaki Tamaki.
  • Journal Title: Wound Repair and Regeneration Volume: 印刷中 Issue: 2 Pages: 217-223
  • DOI: 10.1111/wrr.12510
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 虚血性皮弁壊死モデルにおける抗酸化薬ニトロソニフェジピンの壊死抑制効果 (2016)
  • Author(s): 福永 豊, 石澤 有紀, 堀ノ内 裕也, 池田 康将, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃, 橋本一郎
  • Organizer: 日本形成外科学会基礎学術集会
  • Place of Presentation: ナレッジキャピタルコングレコンベンションセンター(大阪府大阪市)
  • Year and Date: 2016-10-16
• [Presentation] Topical Application of Nitrosonifedipine, a Novel Free Radical Scavenger, Ameliorate the Ischemic Skin Flap Necrosis (2016)
  • Author(s): Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki, Ichiro Hashimoto
  • Organizer: Plastic surgery the meeting 2016
  • Place of Presentation: Los Angeles(アメリカ合衆国)
  • Year and Date: 2016-09-24
  • Int'l Joint Research