title: Alleviation of cisplatin-induced acute kidney injury using phytochemical polyphenols is accompanied by reduced accumulation of indoxyl sulfate in rats.
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.
  
  
  CONCLUSIONS
  Inhibition of IS accumulation by oral administration of quercetin alleviates cisplatin-induced AKI.
authors.affiliation: Department of Clinical Pharmaceutical Sciences, Kumamoto University Graduate School of Pharmaceutical Sciences, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kusumoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kamobayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Megumi
authors.initials: M
authors.lastname: Komori
authors.forename: Misato
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Kohda
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007200:Indican / Q000097:blood / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D059808:Polyphenols / Q000008:administration & dosage / Q000494:pharmacology*; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D002945:Cisplatin; D003404:Creatinine; D007200:Indican; D008315:Malondialdehyde; D059808:Polyphenols; D011794:Quercetin; C110936:Havcr1 protein, rat