Investigation on efficacy of folic acid in methotrexate-induced lung injury for development of pulmonary administration of folate

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18945
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: Kawami Masashi 広島大学, 医系科学研究科(薬), 助教 (20725775)
• Research Collaborator: TAKANO Mikihisa ; YUMOTO Ryoko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 薬剤性肺障害 / メトトレキサート / 葉酸製剤 / 上皮間葉転換 / 肺胞上皮細胞

Outline of Final Research Achievements

Effect of folic acid (FA) and the intratracheal administration on methotrexate (MTX)-induced lung injury was examined. We have found that MTX-induced epithelial-mesenchymal transition (EMT), which is closely related to pulmonary fibrosis, was completely suppressed by the co-treatment with FA, which effect may be based on an inhibitory effect of FA on increase in secretion of EMT-inducing factors from MTX-treated cells. In mouse models, furthermore, intratracheal administration of FA tended to ameliorate MTX-induced inflammation in the lungs. These findings suggest high efficiency of FA in MTX-induced lung injury, and provide significant basic information to develop novel dosage form of FA in clinical use.

Free Research Field

生物薬剤学

Academic Significance and Societal Importance of the Research Achievements

これまでMTXによる肺障害に対して葉酸製剤の使用は推奨されていなかったが、本研究の成果によって、葉酸はMTXによる肺障害に対して有効である可能性が示された。実際に臨床で用いられてこなかった理由として、MTXと比べて葉酸が肺に移行しにくい可能性も考えられたため、新たに葉酸の経肺投与をMTX誘発性肺障害モデルマウスを用いて検討し、良好な結果がえられつつある。本研究の成果によって、MTX誘発性肺障害に対する葉酸の新規経肺投与製剤が有用である可能性が示された。