Novel strategy for development of suppressive drugs for kidney disease based on inhibition of metabolic production of uremic toxins

基于抑制尿毒症毒素代谢产生的肾脏疾病抑制药物开发新策略

• 批准号: 21390048
• 负责人: SAITO Hideyuki
• 金额: $ 11.56万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390048/
• 关键词: 急性腎障害; 慢性腎不全; 尿毒症物質; 腎尿細管; 腎障害; インドキシル硫酸; 腎虚血; シスプラチン; 酸化ストレス; 薬物排泄; 薬物トランスポータ; 虚血

This study was aimed to explore inhibitors of hepatic production of indoxyl sulfate based on uremic toxins which are involved in renal dysfuntion and kidney injury with uremia. By using the screening system for indoxyl sulfate production inhibitors, we found that polyphenolic compounds had potent inhibitory effects on hepatic indoxyl sulfate production. Administration of these polyphenols to rats with acute kidney injury ameliorated the disturbed renal function, suggesting that these approaches could be a useful strategy to develop therapeutic drugs for kidney injuries and/or dieases.

本研究旨在探索基于尿毒症毒素的肝脏产生硫酸吲哚酚的抑制剂，该毒素参与尿毒症的肾功能障碍和肾损伤。通过硫酸吲哚酚生成抑制剂筛选系统，我们发现多酚类化合物对肝脏硫酸吲哚酚生成具有较强的抑制作用。对患有急性肾损伤的大鼠施用这些多酚可以改善肾功能紊乱，这表明这些方法可能是开发肾损伤和/或疾病治疗药物的有用策略。

项目成果

Pathophysiological regulation of renal SLC22A organic ion transporters in acute kidney injury : pharmacological and toxicological implications

肾 SLC22A 有机离子转运蛋白在急性肾损伤中的病理生理调节：药理学和毒理学意义

• 发表时间: 2010
• 作者: Saito H

Contribution of BCR-ABL-independent activation of ERK1/2 to acquired imatinib resistance in K562 chronic myeloid leukemia cells

BCR-ABL 独立的 ERK1/2 激活对 K562 慢性粒细胞白血病细胞获得性伊马替尼耐药的贡献

• 发表时间: 2010
• 作者: Nanbu T; et al.
• 通讯作者: et al.

薬物トランスポーター活用ライブラリー:機能・輸送基質から創薬・臨床応用まで

药物转运蛋白利用库：从功能和转运底物到药物发现和临床应用

• 发表时间: 2009
• 作者: 齋藤秀之; 他
• 通讯作者: 他

Alleviation of cisplatin-induced acute kidney injury using phytochemical polyphenols is accompanied by reduced accumulation of indoxyl sulfate in rats

使用植物化学多酚缓解顺铂引起的急性肾损伤，同时减少大鼠硫酸吲哚酚的积累

• 发表时间: 2011
• 影响因子: 2.3
• 作者: Kusumoto M; Kamobayashi H; Sato D; Komori M; Yoshimura M; Hamada A; Kohda Y; Tomita K; Saito H
• 通讯作者: Saito H

Genetic variation in the organic cation transporter 2(OCT2) influences the cisplatininduced nephrotoxicity in cancer patients

有机阳离子转运蛋白2（OCT2）的遗传变异影响癌症患者顺铂诱导的肾毒性

• 发表时间: 2011
• 作者: Iwata K; et al.
• 通讯作者: et al.