caa a22 4500 445882700 CHVBK 20180317145549.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10157-011-0524-z doi (NATIONALLICENCE)springer-10.1007/s10157-011-0524-z Alleviation of cisplatin-induced acute kidney injury using phytochemical polyphenols is accompanied by reduced accumulation of indoxyl sulfate in rats [Elektronische Daten] [Masahiro Kusumoto, Hiroki Kamobayashi, Daisuke Sato, Megumi Komori, Misato Yoshimura, Akinobu Hamada, Yukimasa Kohda, Kimio Tomita, Hideyuki Saito] 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 (10mg/kg body weight) by intraperitoneal injection. Polyphenols were orally administered at −24, −1, 24 and 48h before or after cisplatin injection. Serum levels of IS, cisplatin, serum creatinine (SCr), blood urea nitrogen (BUN) and electrolytes were measured. By using an 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 levels, 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. Japanese Society of Nephrology, 2011 Acute kidney injury nationallicence Cisplatin nationallicence Indoxyl sulfate nationallicence Uremic toxins nationallicence Polyphenols nationallicence Kusumoto Masahiro Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut Kamobayashi Hiroki Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut Sato Daisuke Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut Komori Megumi Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut Yoshimura Misato Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut Hamada Akinobu Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut Kohda Yukimasa Department of Nephrology, Faculty of Life Science Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut Tomita Kimio Department of Nephrology, Faculty of Life Science Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut Saito Hideyuki Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut Clinical and Experimental Nephrology Springer Japan 15/6(2011-12-01), 820-830 1342-1751 15:6<820 2011 15 10157 https://doi.org/10.1007/s10157-011-0524-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10157-011-0524-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kusumoto Masahiro Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut NATIONALLICENCE 700 1- Kamobayashi Hiroki Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut NATIONALLICENCE 700 1- Sato Daisuke Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut NATIONALLICENCE 700 1- Komori Megumi Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut NATIONALLICENCE 700 1- Yoshimura Misato Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan aut NATIONALLICENCE 700 1- Hamada Akinobu Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut NATIONALLICENCE 700 1- Kohda Yukimasa Department of Nephrology, Faculty of Life Science Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut NATIONALLICENCE 700 1- Tomita Kimio Department of Nephrology, Faculty of Life Science Kumamoto University, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut NATIONALLICENCE 700 1- Saito Hideyuki Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, 860-8556, Kumamoto, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Nephrology Springer Japan 15/6(2011-12-01), 820-830 1342-1751 15:6<820 2011 15 10157 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer