Negative correlation between serum uric acid and kidney URAT1 mRNA expression caused by resveratrol in rats

• Published in: Molecular nutrition & food research Vol. 61; no. 10
• Main Authors: Lee, Cheng‐Tse, Chang, Li‐Ching, Liu, Ching‐Wen, Wu, Pei‐Fung
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2017
• Subjects: Alanine; Alanine transaminase; Alanine Transaminase - blood; Allopurinol; Allopurinol - pharmacology; Animals; Anion Transport Proteins - genetics; Anion Transport Proteins - metabolism; Aspartate aminotransferase; Aspartate Aminotransferases - blood; C-Reactive Protein - metabolism; Correlation analysis; Creatinine; Creatinine - blood; Cytokines - blood; Disease Models, Animal; Gene expression; Hyperuricemia; Hyperuricemia - blood; Hyperuricemia - drug therapy; IL‐6; Immunoreactivity; Interleukin 6; Kidney - drug effects; Kidney - metabolism; Kidneys; Male; Potassium; Rats; Rats, Sprague-Dawley; Reabsorption; Resveratrol; RNA, Messenger - genetics; Rodents; Stilbenes - pharmacology; URAT1; Uric acid; Uric Acid - blood; Uric acid; URAT1; Allopurinol; IL-6; Resveratrol
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201601030

Scope This study established a hyperuricemic rat model to elucidate the effect of resveratrol on the transport of UA in the kidney. Methods and results Hyperuricemia was induced in rats through daily oral gavage of a potassium oxonate and UA mixture over 3 weeks. Our results revealed that resveratrol significantly reduced the serum UA levels but not creatinine, c‐creative protein, alanine aminotransferase, or aspartate aminotransferase levels in these rats. Furthermore, renal URAT1 and OAT1 mRNA expression were significantly higher in the rats treated with allopurinol than in those with no treatment. Therefore, allopurinol not only inhibited UA production but also mediated renal URAT1 and OAT1 expression. The correlation analysis revealed that UA levels correlated negatively with renal IL‐6 mRNA expression in rats treated with allopurinol. Moreover, URAT1 showed strong immunoreactivity in the distal convoluted tubule of rats treated with allopurinol or resveratrol and in hyperuricemic treated with allopurinol. Finally, in the rats treated with resveratrol, UA levels correlated negatively with renal URAT1 mRNA expression; thus, resveratrol reduced URAT1 mRNA expression under high UA levels, thereby reducing UA reabsorption in renal cells. Conclusion Resveratrol contributes to URAT1 expression, which is potentially useful in therapeutic strategies aimed at treating hyperuricemia. Immunohistochemical staining shows strong immunoreactivity of URAT1 in the distal convoluted tubule in rats treated with allopurinol or resveratrol and in hyperuricemic rats treated with allopurinol, indicating that resveratrol contributes URAT1 expression in rat kidneys.