1. Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice.
- Author
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Hu QH, Zhang X, Wang X, Jiao RQ, and Kong LD
- Subjects
- Allopurinol pharmacology, Animals, Blood Urea Nitrogen, Carrier Proteins genetics, Carrier Proteins metabolism, Creatinine blood, Disease Models, Animal, Glucose Transport Proteins, Facilitative genetics, Glucose Transport Proteins, Facilitative metabolism, Hyperuricemia physiopathology, Kidney drug effects, Kidney metabolism, Male, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Octamer Transcription Factor-1 genetics, Octamer Transcription Factor-1 metabolism, Organic Anion Transport Protein 1 genetics, Organic Anion Transport Protein 1 metabolism, Organic Anion Transporters genetics, Organic Anion Transporters metabolism, Organic Cation Transport Proteins genetics, Organic Cation Transport Proteins metabolism, Organic Cation Transporter 2, RNA, Messenger genetics, RNA, Messenger metabolism, Solute Carrier Family 22 Member 5, Symporters, Uric Acid blood, Urinary Tract Physiological Phenomena drug effects, Uromodulin genetics, Gene Expression Regulation, Hyperuricemia drug therapy, Quercetin pharmacology, Uromodulin blood, Uromodulin urine
- 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., Purposes: 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.
- Published
- 2012
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