Dietary Flavonoid Quercetin Exhibits Uricosuric and Renal Protective Actions in Hyperuricemic Rodents: Renal Organic Ion Transporter Involvement

Hyperuricemia is a common biochemical abnormality generally associated with the development of renal dysfunction, gout, hypertension, hyperlipidemia, diabetes and obesity [1–2]. The impaired renal excretion of uric acid is an important cause of hyperuricemia. The urate excretion process mainly depends on the renal SLC2A and SLC22A family of organic ion transporters [3–4]. Renal organic cation and carnitine transporters (OCTs and OCTNs) are responsible for renal uptake and excretion of organic cations [5]. Therefore, these organic ion transporters as the effective molecular targets in renal urate transport and function are the appropriate experimental models for investigating the pathophysical mechanisms of hyperuricemia and developing hypouricemic drugs. Dietary flavonoid quercetin present in various fruits and vegetables exerts beneficial effects on human health. We examined whether quercetin will have effects on dysregulation of renal organic ion transporters in hyperuricemic rodents and explored the potential mechanisms involved. In this study, quercetin increased urate excretion and reduced serum urate level, as well as down-regulated renal expression levels of GLUT9 (SLC2A9) and URAT1 (SLC22A12) in hyperuricemic animals. Quercetin reduced serum creatinine and blood urea nitrogen levels, and up-regulated renal OCT1–2 (SLC22A1–2) and OCTN1–2 (SLC22A4–5). These results provide evidence that quercetin has uricosuric effects and protects against kidney dysfunction in hyperuricemia mediated by regulation of these renal organic ion transporters. Dietary quercetin may have potential for the prevention of hyperuricemia with kidney dysfunction. Acknowledgements: This study is supported by grants from National Natural Science Foundation of China (NSFC 81025025 and J1103512), Jiangsu Natural Science Foundation (BK 2010365) and Program for Changjiang Scholars and Innovative Research Team in University (IRT1020). References: [1] Feig DI, et al., (2008) N Engl J Med 359: 1811–1821. [2] Richette P, Bardin T (2010) Lancet 375: 318–328. [3] Preitner F, et al. (2009) Proc Natl Acad Sci U S A 106: 15501–15506. [4] Enomoto A, et al. (2002) Nature 417: 447–452. [5] Motohashi H, et al. (2002) JASN 13: 866–874.