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.

本研究的目的是探索基于尿毒症毒素的硫酸吲哚酚肝生成抑制剂，这些毒素参与尿毒症肾功能障碍和肾损伤。通过使用硫酸吲哚酚产生抑制剂的筛选系统，我们发现多酚类化合物对肝脏硫酸吲哚酚产生具有有效的抑制作用。给予急性肾损伤大鼠这些多酚改善了肾功能紊乱，这表明这些方法可能是一个有用的策略，以开发治疗药物的肾损伤和/或疾病。

项目成果

Enhanced renal accumulation of cisplatin via renal organic cation transporter deteriorates acute kidney injury in hypomagnesemic rats

• DOI: 10.1007/s10157-009-0215-1
• 发表时间: 2009-12-01
• 期刊: CLINICAL AND EXPERIMENTAL NEPHROLOGY
• 影响因子: 2.3
• 作者: Yokoo, Koji;Murakami, Risa;Saito, Hideyuki
• 通讯作者: Saito, Hideyuki

P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines.

• DOI: 10.1248/bpb.32.1588
• 发表时间: 2009-09
• 期刊: Biological & pharmaceutical bulletin
• 影响因子: 2
• 作者: Fujimoto H;Higuchi M;Watanabe H;Koh Y;Ghosh AK;Mitsuya H;Tanoue N;Hamada A;Saito H
• 通讯作者: Saito H

腎機能低下に伴う経口分子標的治療薬の動態変動と影響因子

口服分子靶向治疗药物与肾功能下降的动力学变化及影响因素

• 发表时间: 2011
• 作者: Fujita;A.;Cheng;J.;Fujimoto;T.;齋藤秀之
• 通讯作者: 齋藤秀之

Distinct transport characteristics of platinum anticancer drugs, cisplatin and oxaliplatin, in renal tubular epithelial cell line LLC-PK_1 via organic cation transporter and copper transporter

铂类抗癌药物顺铂和奥沙利铂在肾小管上皮细胞系 LLC-PK_1 中通过有机阳离子转运蛋白和铜转运蛋白的独特转运特性

• 发表时间: 2009
• 作者: 牛木辰男;他(招待講演);Saito H.
• 通讯作者: Saito H.

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

• DOI: 10.1111/j.1349-7006.2009.01365.x
• 发表时间: 2010-01-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Nambu, Takeru;Araki, Norie;Saito, Hideyuki
• 通讯作者: Saito, Hideyuki