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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F1080    most recent 90767.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hu, Q.-H. Articles by Kong, L.-D. PubMed PubMed Citation Articles by Hu, Q.-H. Articles by Kong, L.-D.

Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

Submitted December 23, 2008 ; accepted in final form August 7, 2009

Fructose consumption has been recently related to an epidemic of metabolic syndrome, and hyperuricemia plays a pathogenic role in fructose-induced metabolic syndrome. Fructose-fed rats showed hyperuricemia and renal dysfunction with reductions of the urinary uric acid/creatinine ratio and fractional excretion of uric acid (FE_ur), as well as other features of metabolic syndrome. Lowering serum uric acid levels with allopurinol, rutin, and quercetin increased the urinary uric acid/creatinine ratio and FE_ur and attenuated other fructose-induced metabolic abnormalities in rats, demonstrating that hyperuricemia contributed to the deficiency of renal uric acid excretion in this model. Furthermore, we found that fructose upregulated the expression levels of rSLC2A9v2 and renal-specific transporter (rRST), downregulated the expression levels of organic anion transporters (rOAT1 and rUAT) and organic cation transporters (rOCT1 and rOCT2), with the regulators prostaglandin E₂ (PGE₂) elevation and nitric oxide (NO) reduction in rat kidney. Allopurinol, rutin, and quercetin reversed dysregulations of these transporters with PGE₂ reduction and NO elevation in the kidney of fructose-fed rats. These results suggested that dysregulations of renal rSLC2A9v2, rRST, rOAT1, rUAT, rOCT1, and rOCT2 contributed to fructose-induced hyperuricemia and renal dysfunction. Therefore, these renal transporters may represent novel therapeutic targets for the treatment of hyperuricemia and renal dysfunction in fructose-induced metabolic syndrome.

high uric acid; rSLC2A9; rUAT; rSLC22A; hypouricemic agents