Improvement of inflammatory bowel diseases based on expression and functional changes of P-glycoprotein by methyl prednisolone and essential unsaturated fatty acids

• Project/Area Number: 24590216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tohoku Pharmaceutical University (2014); Tokyo University of Pharmacy and Life Science (2012)
• Principal Investigator: TOMITA MIKIO 東北薬科大学, 薬学部, 教授 (60207610)
• Co-Investigator(Kenkyū-buntansha): 瀧沢 裕輔 東京薬科大学, 薬学部, 助教 (40453807)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 炎症性腸疾患 / Methylprednisolone / P-glycoprotein / 薬物療法 / 栄養療法 / 必須不飽和脂肪酸 / Dextran sodium sulfate

Outline of Final Research Achievements

Linoleic acid (LA) and α-linolenic acid (α-LnA) decrease the absorption of methylprednisolone (MP) from small intestine in inflammatory bowel disease (IBD) model rats and have delivery effects to large intestine to MP. LA and α-LnA have anti-inflammatory effects and regulatory effects on expression and function of P-glycoprotein (P-gp) in small intestine. It suggests that administration of these essential unsaturated fatty acids not only prevent progress of IBD and but also normalize intestinal absorption and disposition of the drug which is a substrate of P-gp in vivo. More experimental information and data are necessary for more efficient administration schedule of drugs in IBD therapy.

Research Products

• [Journal Article] Changes in the expression levels of tight junction components during reconstruction of tight junction from mucosal lesion by intestinal ischemia/reperfusion (2014)
  • Author(s): Y. Takizawa, H. Kishimoto, M. Tomita, M. Hayash
  • Journal Title: European Journal of Drug Metabolism and Pharmacokinetics Volume: 39 Issue: 3 Pages: 211-220
  • DOI: 10.1007/s13318-013-0151-z
  • Peer Reviewed
• [Presentation] 尿毒症物質インドキシル硫酸の消化管粘膜透過機構の解析 (2014)
  • Author(s): 宮本将成，我妻雄太，野呂悠佳，森本かおり，矢野健太郎，荻原琢男，富田幹雄
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき明星大学キャンパス
  • Year and Date: 2014-10-05
• [Presentation] 必須不飽和脂肪酸による-糖タンパク質の機能ならびに構造変化 (2014)
  • Author(s): 横田 隼人, 飯田 遼，熊谷 茉歩，森本 かおり，伊藤 邦郎, 富田 幹雄
  • Organizer: 第53回日本薬学会東北支部大会
  • Place of Presentation: いわき明星大学キャンパス
  • Year and Date: 2014-10-05
• [Presentation] 必須不飽和脂肪酸によるP-糖タンパク質の機能ならびに構造変化 (2014)
  • Author(s): 飯田 遼，我妻 雄太，森本 かおり，富田 幹雄
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 慶應義塾大学 薬学部 芝共立キャンパス
  • Year and Date: 2014-07-30 – 2014-07-31
• [Presentation] 尿毒症物質によるMRP2ならびにBCRPの阻害 (2014)
  • Author(s): 我妻 雄太, 飯田 遼, 森本 かおり, 富田 幹雄
  • Organizer: 日本薬剤学会29年会
  • Place of Presentation: 大宮ソニックシティビル
  • Year and Date: 2014-05-21 – 2014-05-23