title: Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice.
abstract: BACKGROUND
  Renal organic ion transporters and uromodulin (UMOD) play the important roles in renal urate excretion and function. Hyperuricemia is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin in diets exerts the hypouricemic and nephroprotective effects.
  
  
  OBJECTIVE
  To evaluate the effects of quercetin on renal organic ion transporters and UMOD in hyperuricemic mice.
  
  
  METHODS
  Kun-Ming mice were divided into normal and hyperuricemic groups receiving water, 25, 50 and 100 mg/kg quercetin, 5 mg/kg allopurinol, respectively. Hyperuricemic mice were orally gavaged with 250 mg/kg oxonate daily for 1 week. Quercetin and allopurinol were orally gavaged on the day when oxonate or water was given 1 h later. After 1 week, serum uric acid, creatinine and blood urea nitrogen concentrations, excretion of urate and creatinine, and fractional excretion of uric acid were measured. The mRNA and protein levels of renal urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in mice were analyzed. Simultaneously, UMOD levels in serum, urine and kidney, as well as renal UMOD mRNA expression were detected.
  
  
  RESULTS
  Quercetin significantly restored oxonate-induced abnormalities of these biochemical indexes compared with normal vehicle group. Furthermore, it remarkably prevented expression changes of renal organic ion transporters and UMOD, and UMOD level alteration in hyperuricemic mice.
  
  
  CONCLUSIONS
  These results suggest that quercetin has the uricosuric and nephroprotective actions mediated by regulating the expression levels of renal organic ion transporters and UMOD.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, People's Republic of China.
authors: Qing-Hua
authors: QH
authors: Hu
authors: Xian
authors: X
authors: Zhang
authors: Xing
authors: X
authors: Wang
authors: Rui-Qing
authors: RQ
authors: Jiao
authors: Ling-Dong
authors: LD
authors: Kong
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001806:Blood Urea Nitrogen; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D033461:Hyperuricemia / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014527:Uric Acid / Q000097:blood; D014553:Urinary Tract Physiological Phenomena / Q000187:drug effects; D058949:Uromodulin / Q000097:blood* / Q000235:genetics / Q000652:urine*
chemical_list: D002352:Carrier Proteins; D051246:Glucose Transport Proteins, Facilitative; D008565:Membrane Proteins; D050811:Octamer Transcription Factor-1; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C494166:Pou2f1 protein, mouse; D012333:RNA, Messenger; C109687:Slc22a12 protein, mouse; C491012:Slc22a2 protein, mouse; C491659:Slc22a4 protein, mouse; C492019:Slc22a5 protein, mouse; C105033:Slc22a6 protein, mouse; C498775:Slc2a9 protein, mouse; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; C548613:Umod protein, mouse; D058949:Uromodulin; D014527:Uric Acid; D000493:Allopurinol; D011794:Quercetin; D003404:Creatinine