title: Morin improves urate excretion and kidney function through regulation of renal organic ion transporters in hyperuricemic mice.
abstract: OBJECTIVE
  Morin (2′,3,4′,5,7-pentahydroxyflavone), a plant-derived flavonoid, has beneficial effects on hyperuricemia and renal dysfunction in animals. Since the decreased renal excretion of uric acid is the hallmark of hyperuricemia, here we studied the effects of oral morin administration on renal organic ion transporters in potassium oxonate-induced hyperuricemic mice.
  
  
  METHODS
  Hyperuricemia in mice was induced by potassium oxonate. Uric acid and creatinine concentrations in urine and serum, and fractional excretion of uric acid (FEUA) were performed to evaluate renal urate handling. Changes in expression levels of renal organic ion transporters were detected by Western blotting and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) methods.
  
  
  RESULTS
  Morin treatment significantly increased urinary uric acid/creatinine ratio and FEUA, resulting in reduction of serum uric acid levels in hyperuricemic mice. And kidney conditions were also improved after morin treatment in this model. Protein and mRNA levels of glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1) were significantly decreased, and of organic anion transporter 1 (mOAT1) were remarkably increased in the kidney of morin-treated hyperuricemic mice. Morin treatment also blocked down-regulations of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in hyperuricemic mice.
  
  
  CONCLUSIONS
  These results suggest that morin exhibits the uricosuric effects via suppressing urate reabsorption and promoting urate secretion in the kidney of hyperuricemic mice and may help to attenuate deleterious effects of hyperuricemia with renal dysfunction.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P. R. China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage* / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D033461:Hyperuricemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood / Q000378:metabolism / Q000652:urine*; D014553:Urinary Tract Physiological Phenomena; D047309:Flavones
chemical_list: D003404:Creatinine; D005419:Flavonoids; D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; D014527:Uric Acid; C109687:Slc22a12 protein, mouse; C498775:Slc2a9 protein, mouse; C008548:morin; D047309:Flavones