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Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats
http://hdl.handle.net/10076/00019579
http://hdl.handle.net/10076/000195797758892e-b228-49d1-b289-4b96e602ee5c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2020DM0914 (547.4 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2021-01-05 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | cisplatin | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | lansoprazole | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | nephrotoxicity | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | organic cation transporter 2 | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
平松, 駿一
× 平松, 駿一
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Cisplatin is widely used for the treatment of multiple solid tumors. Cisplatin-induced nephrotoxicity is caused by renal accumulation of cisplatin via human organic cation transporter 2 (hOCT2). As lansoprazole (LPZ), a proton pump inhibitor (PPI), is known to inhibit hOCT2 activity, LPZ might ameliorate cisplatin-induced nephrotoxicity. Previous study showed that concomitant LPZ administration ameliorated nephrotoxicity in patients receiving cisplatin. However, the detailed mechanism remains to be clarified. In the present study, the drug-drug interaction between LPZ and cisplatin was examined using hOCT2-expressing cultured cells and rat renal slices. Moreover, we investigated the effect of LPZ on cisplatin-induced nephrotoxicity and pharmacokinetics of cisplatin in rats. In the uptake study, LPZ potently inhibited uptake of cisplatin in hOCT2-expressing cultured cells and rat renal slices. In vivo rat study showed that concomitant LPZ significantly ameliorated cisplatin-induced nephrotoxicity and reduced renal accumulation of platinum (Pt) up to approximately 60% of cisplatin alone at 72 h after cisplatin intraperitoneal administration. Furthermore, renal uptake of Pt at 3 min after intravenous cisplatin administration in rats with cisplatin and LPZ decreased to 78% of rats with cisplatin alone. In addition, there was no significant difference in plasma Pt concentration between rats treated with and without LPZ at 3 min after cisplatin intravenous administration. These findings suggested that concomitant LPZ ameliorated cisplatin-induced nephrotoxicity by inhibiting rOCT2-mediated cisplatin uptake in rats, thus decreasing cisplatin accumulation in the kidney. The present findings provided important information for the establishment of novel protective approaches to minimize cisplatin-induced nephrotoxicity. | |||||||||||
| 言語 | en | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文/Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 33p | |||||||||||
| 書誌情報 |
発行日 2020-09-16 |
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| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1002/bdd.2242 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| 値 | ミエダイガク | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2020-09-16 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第2035号 | |||||||||||
| ノート | ||||||||||||
| 資源タイプ（三重大） | ||||||||||||
| 値 | Doctoral Dissertation / 博士論文 | |||||||||||
