Morin Improves Urate Excretion and Kidney Function through Regulation of Renal Organic Ion Transporters in Hyperuricemic Mice

Abstract

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. 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. 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. 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.