Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement.
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 E(2) (PGE(2)) elevation and nitric oxide (NO) reduction in rat kidney. Allopurinol, rutin, and quercetin reversed dysregulations of these transporters with PGE(2) 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.
Hu
Qing-Hua
QH
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Wang
Chuang
C
Li
Jian-Mei
JM
Zhang
Dong-Mei
DM
Kong
Ling-Dong
LD
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D004040:Dietary Carbohydrates / Q000009:adverse effects; D015232:Dinoprostone / Q000378:metabolism; D005632:Fructose / Q000009:adverse effects*; D033461:Hyperuricemia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D027361:Organic Anion Transporters / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D011794:Quercetin / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000627:therapeutic use; D014527:Uric Acid / Q000652:urine; D014528:Uricosuric Agents / Q000627:therapeutic use
D000975:Antioxidants; D004040:Dietary Carbohydrates; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D014528:Uricosuric Agents; D014527:Uric Acid; D005632:Fructose; D009569:Nitric Oxide; D012431:Rutin; D000493:Allopurinol; D011794:Quercetin; D015232:Dinoprostone