Protective Effect of Dimethyl Fumarate on an Oxidative Stress Model Induced by Sodium Nitroprusside in Mice

• Kume Toshiaki

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Suenaga Aya

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Izumi Yasuhiko

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Akaike Akinori

  Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University Laboratory of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University

抄録

Recent reports have shown that dimethyl fumarate (DMF) prevents brain damage induced by intracerebral hemorrhage and this beneficial effect is mediated by the nuclear erythroid 2 p45-related factor-2–antioxidant response element (Nrf2–ARE) pathway. However, the downstream mechanism underlying the activation of the Nrf2–ARE pathway is unclear. Here, we investigated the protective effect of DMF using an in vivo model of oxidative stress induced by sodium nitroprusside (SNP) and rat primary striatal cultures. Oral administration of DMF prevented SNP-induced motor dysfunction. Pre-administration of DMF (60–200 mg/kg) for 24 h dose-dependently protected against brain damage induced by the striatal injection of SNP. Next, we investigated the protective effect and mechanism of DMF against oxidative stress using rat primary striatal cell cultures. Treatment of striatal cells with DMF (10 µM) markedly prevented hydrogen peroxide-induced cytotoxicity. The protective effect of DMF against oxidative stress in vitro was inhibited by zinc protoporphyrin IX, an inhibitor of heme oxygenase-1, but not by buthionine sulfoximine, an inhibitor of glutathione synthesis. These results suggest that the activation of heme oxygenase-1 plays an important role in the protective effect of DMF.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 39 (6), 1055-1059, 2016

  公益社団法人 日本薬学会

キーワード

• dimethyl fumarate
• oxidative stress
• brain
• nuclear erythroid 2 p45-related factor-2–antioxidant response element (Nrf2–ARE) pathway
• sodium nitroprusside

詳細情報

• CRID: 1390282679609916288
• NII論文ID: 130005155120
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b16-00134
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 027325499
• PubMed: 27251510
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027325499
• Web Site: https://www.jstage.jst.go.jp/article/bpb/39/6/39_b16-00134/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017021114
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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