Original Article

Clinical and Experimental Nephrology

, Volume 15, Issue 6, pp 820-830

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

  • Masahiro KusumotoAffiliated withDepartment of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences
  • , Hiroki KamobayashiAffiliated withDepartment of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences
  • , Daisuke SatoAffiliated withDepartment of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences
  • , Megumi KomoriAffiliated withDepartment of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences
  • , Misato YoshimuraAffiliated withDepartment of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences
  • , Akinobu HamadaAffiliated withDepartment of Pharmacy, Kumamoto University Hospital
  • , Yukimasa KohdaAffiliated withDepartment of Nephrology, Faculty of Life Science Kumamoto University
  • , Kimio TomitaAffiliated withDepartment of Nephrology, Faculty of Life Science Kumamoto University
  • , Hideyuki SaitoAffiliated withDepartment of Pharmacy, Kumamoto University Hospital Email author 

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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 h 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.

Keywords

Acute kidney injury Cisplatin Indoxyl sulfate Uremic toxins Polyphenols