Effect of a Selective Inhibitor of Secretory Phospholipase A2, S-5920/LY315920Na, on Experimental Acute Pancreatitis in Rats

• Tomita Yasuhiko

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Kuwabara Kenji

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Furue Shingo

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Tanaka Kazushige

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Yamada Katsutoshi

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Ueno Masahiko

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Ono Takashi

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Maruyama Toshiyuki

  Discovery Research Laboratories, Shionogi & Co., Ltd.

• Ajiki Tetsuo

  The First Department of Surgery, Kobe University School of Medicine

• Onoyama Hirohiko

  The First Department of Surgery, Kobe University School of Medicine

• Yamamoto Masahiro

  The First Department of Surgery, Kobe University School of Medicine

• Hori Yozo

  Discovery Research Laboratories, Shionogi & Co., Ltd.

抄録

We investigated the efficacy of a potent inhibitor of secretory phospholipase A₂ (sPLA₂), S-5920/LY315920Na, in an experimental model of acute pancreatitis in rats. Combined intraductal injection of sodium taurocholate (5 mg/rat) and porcine pancreatic sPLA₂-IB (300 μg/rat) caused severe hemorrhagic necrotizing pancreatitis resulting in high mortality, along with rapid increases of catalytic PLA₂ and lipase activities in plasma and ascites and with gradual increases of plasma amylase and aspartate aminotransferase levels over 9 h after the pancreatitis. Prophylactic intravenous treatment with S-5920/LY315920Na significantly reduced mortality at 7 days, and strongly abrogated PLA₂ activities in both plasma and ascites along with significant reduction of lipase activity, amylase, aspartate aminotransferase, and hemorrhage at 6 h. It also significantly reduced histological damage such as edema and parenchymal and fat necroses of the pancreatic tissue. This sPLA₂ inhibitor could become an effective agent for the treatment of severe acute pancreatitis.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 96 (2), 144-154, 2004

  公益社団法人 日本薬理学会

キーワード

• phospholipase A₂
• pancreatitis
• parenchymal necrosis
• S-5920/LY315920Na

詳細情報

• CRID: 1390282680152309632
• NII論文ID: 10014166632
• NII論文ID: 130000074194
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.fp0040314
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 7120702
• PubMed: 15467263
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7120702
• Web Site: https://search.jamas.or.jp/link/ui/2006060003
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可