Involvement of multidrug resistance-associated protein 1 in intestinal toxicity of methotrexate.
スポンサーリンク
概要
- 論文の詳細を見る
最終稿を登録可能.Purpose: Methotrexate (MTX) causes dose-limiting gastrointestinal toxicity due to exposure of intestinal tissues, and is a substrate of the multidrug resistance-associated protein (MRP) 1. Here we examine the involvement of MRP1, which is reported to be highly expressed in the proliferative crypt compartment of the small intestine, in the gastrointestinal toxicity of MTX. Methods: MTX was intraperitonealy administered to mrp1 gene knockout (mrp1 (-/-)) and wild-type (mrp1 (+/+)) mice. Body weight, food and water intake were monitored, intestinal histological studies and pharmacokinetics of MTX were examined. Results: mrp1 (-/-) mice more severely decreased body weight, food and water intake than mrp1 (+/+) mice. Almost complete loss of villi throughout the small intestine in mrp1 (-/-) mice was observed, whereas the damage was only partial in mrp1 (+/+) mice. Plasma concentration and biliary excretion profiles of MTX were similar in mrp1 (-/-) and mrp1 (+/+) mice, though accumulation of MTX in immature proliferative cells isolated from mrp1 (-/-) mice was much higher compared to mrp1 (+/+) mice. Immunostaining revealed localization of Mrp1 in plasma membrane of the intestinal crypt compartment in mrp1 (+/+) mice, but not in mrp1 (-/-) mice. Conclusion: Mrp1 determines the exposure of proliferative cells in the small intestine to MTX, followed by gastrointestinal toxicity. © 2009 Springer Science+Business Media, LLC.
論文 | ランダム
- 佐賀藩の宗教政策--願正寺文書を通してみたる
- フェートン号事件と佐賀藩(研究余録)
- 慶応三年パリ万国博覧会に関する新史料
- 暗闇に走らせた鉛筆,散策の手帳 最後のテ-マは「生命の発生」--故・福井謙一博士の思考法をたどる
- コミュニケーションとしてのディスクロージャー