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.
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 flavonoidquercetin in diets exerts the hypouricemic and nephroprotective effects. PURPOSES: To evaluate the effects of quercetin on renal organic ion transporters and UMOD in hyperuricemicmice. 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. Hyperuricemicmice 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 ureanitrogen 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 hyperuricemicmice. 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: M Harwood; B Danielewska-Nikiel; J F Borzelleca; G W Flamm; G M Williams; T C Lines Journal: Food Chem Toxicol Date: 2007-06-07 Impact factor: 6.023
Authors: Magdalena Cristóbal-García; Fernando E García-Arroyo; Edilia Tapia; Horacio Osorio; Abraham S Arellano-Buendía; Magdalena Madero; Bernardo Rodríguez-Iturbe; José Pedraza-Chaverrí; Francisco Correa; Cecilia Zazueta; Richard J Johnson; Laura-Gabriela Sánchez Lozada Journal: Oxid Med Cell Longev Date: 2015-03-31 Impact factor: 6.543