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Alleviation of cisplatin-induced acute kidney injury using phytochemical polyphenols is accompanied by reduced accumulation of indoxyl sulfate in rats 楠本, 将裕 鴨林, 宏樹 カモバヤシ, ヒロキ Kamobayashi, Hiroki 鴨林 カモバヤシ Kamobayashi 宏樹 ヒロキ Hiroki 佐藤, 大介 小森, めぐみ 脇田, 紋佳 吉村, 美里 濱田, 哲暢 江​田, ​幸​政 冨田, 公夫 齋藤, 秀之 Kusumoto, Masahiro 鴨林, 宏樹 カモバヤシ, ヒロキ Kamobayashi, Hiroki 鴨林 カモバヤシ Kamobayashi 宏樹 ヒロキ Hiroki Sato, Daisuke Komori, Megumi Wakida, Ayaka Yoshimura, Misato 濱田, 哲暢 ハマダ, アキノブ Hamada, Akinobu 濱田 ハマダ Hamada 哲暢 アキノブ Akinobu Kohda, Yukimasa Tomita, Kimio Saito, Hideyuki 499 Acute kidney injury Cisplatin Indoxyl sulfate Uremic toxins Phytochemical polyphenols application/pdf 論文(Article) Background:Polyphenols such as quercetin have been reported to prevent cisplatin-induced acute kidney injury (AKI). Indoxyl sulfate (IS), a uremic toxin generated in the liver, is increased in cisplatin AKI. The present study examined the effect of phytochemical polyphenols on serum and renal accumulations of IS in association with cisplatin AKI. Methods:Sprague-Dawley rats were treated with cisplatin (10 mg/kg body weight) by intraperitoneal injection. Polyphenols were orally administered at -24, -1, 24 and 48 hr before or after cisplatin injection. Serum levels of IS, cisplatin, serum creatinine (SCr), blood urea nitrogen (BUN) and electrolytes were measured. By using in vitro assay system with rat liver S9 fraction, the inhibitory potencies of several compounds on IS production were determined. Results:Injection of cisplatin in rats markedly elevated the SCr and BUN levles, which were accompanied by tubular injuries and the expression of kidney injury molecule-1 (Kim-1). By contrast, quercetin significantly suppressed the SCr and BUN levels in the cisplatin-treated rats and protected them against renal injury with the decreased expression of Kim-1. Quercetin had no effect on serum and renal levels of cisplatin. In addition, quercetin had no effect on cisplatin-induced renal accumulation of malondialdehyde. IS concentrations in serum, kidney, liver, intestine and lung were markedly elevated by cisplatin treatment, whereas quercetin suppressed the serum and tissue IS levels. An in vitro kinetic assay revealed that quercetin displayed a potent inhibitory effect on hepatic production of IS. Conclusion:Inhibition of IS accumulation by oral administration of quercetin alleviates cisplatin-induced AKI. http://www.springerlink.com/content/051w24k21l103266/ Springer Japan 2011-12 eng journal article AM http://hdl.handle.net/2298/25981 https://kumadai.repo.nii.ac.jp/records/25109 21858734 10.1007/s10157-011-0524-z Clinical and Experimental Nephrology 15 6 820 830 https://kumadai.repo.nii.ac.jp/record/25109/files/Kusumoto CEN FINAL REPOS.pdf application/pdf 657.0 kB 2020-03-02