title: Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.
abstract: A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified.
  
  
  
  We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration.
  
  
  
  Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose.
  
  
  
  Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia.
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kaneko
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Ogura
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan. Electronic address: masaki@pharm.hokudai.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kuwayama
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Narumi
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan; Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan. Electronic address: ken-i@pharm.hokudai.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism; D000818:Animals; D005632:Fructose / Q000378:metabolism*; D033461:Hyperuricemia / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C489249:Abcg2 protein, rat; D009861:Onium Compounds; D014527:Uric Acid; D005632:Fructose; C007517:diphenyleneiodonium; D019255:NADPH Oxidases
keywords: Breast cancer resistance protein; Fructose; Hyperuricemia; NADPH oxidase; Oxidative stress; Uric acid excretion