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タイトル :Alleviation of cisplatin-induced acute kidney injury using phytochemical polyphenols is accompanied by reduced accumulation of indoxyl sulfate in rats
著者 :Kusumoto, Masahiro
Kamobayashi, Hiroki
Sato, Daisuke
Komori, Megumi
Wakida, Ayaka
Yoshimura, Misato
Hamada, Akinobu
Kohda, Yukimasa
Tomita, Kimio
Saito, Hideyuki
刊行年月日 :2011-12
収録雑誌名 :Clinical and Experimental Nephrology
巻 :15
号 :6
開始ページ :820
終了ページ :830
要約(Abstract) :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.
URL :http://www.springerlink.com/content/051w24k21l103266/
収録種別 :雑誌掲載論文
出版社(者) :Springer Japan
URI :http://hdl.handle.net/2298/25981
このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/2298/25981