Abstract
Aims: The aim of the present study was to investigate the effects of rutin on potassium oxonate-induced hyperuricemia and renal dysfunction in mice. Methods: Rutin was administered orally 1 h after oxonate at doses of 25, 50 and 100 mg·kg-1. Serum uric acid levels and kidney function parameters were assayed. Mouse uromodulin levels in serum, urine and kidney were determined by the ELISA method. Simultaneously, the expression levels of renal organic ion transporters were detected. Results: Rutin significantly decreased serum urate, creatinine and blood urea nitrogen, serum and kidney uromodulin levels, and increased urine uromodulin, urate and creatinine excretion in hyperuricemic mice. Rutin at 50 and 100 mg·kg-1 significantly downregulated mRNA and protein levels of mouse glucose transporter 9 and urate transporter 1, and upregulated mRNA and protein levels of organic anion transporter 1 and organic cation/carnitine transporters in the kidney of hyperuricemic mice. Conclusions: Rutin exerted its hypouricemic action and renal function improvement by the regulation of renal organic ion transporters.
Journal Section:
Original Paper
References
1.
Heinig M, Johnson RJ: Role of uric acid in hypertension, renal disease, and metabolic syndrome. Cleve Clin J Med 2006;73:1059-1064.
[PubMed]
2.
Choi HK, Ford ES: Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am J Med 2007;120:442-447.
[PubMed]
3.
Schlesinger N: Management of acute and chronic gouty arthritis: present state-of-the-art. Drugs 2004;64:2399-2416.
[PubMed]
4.
Hammer B, Link A, Wagner A, Böhm M: Hypersensitivity syndrome during therapy with allopurinol in asymptomatic hyperuricemia with a fatal outcome. Dtsch Med Wochenschr 2001;126:1331-1334.
[PubMed]
5.
Terkeltaub RA: Gout. N Engl J Med 2003;349:1647-1655.
6.
Hao HH, Shao ZM, Tang DQ, Lu Q, Chen X, Yin XX, Wu J, Chen H. Preventive effects of rutin on the development of experimental diabetic nephropathy in rats. Life Sci 2012;91:959-67.
[PubMed]
7.
Calabro ML, Tommasini S, Donato P, Stancanelli R, Raneri D, Catania S, Costa C, Villari V, Ficarra P, Ficarra R: The rutin/beta-cyclodextrin interactions in fully aqueous solution: spectroscopic studies and biological assays. J Pharm Biomed Anal 2005;36:1019-1027.
[PubMed]
8.
Middleton E, Kandaswami C, Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharm Rev 2000;52:673-751.
[PubMed]
9.
Ihme N, Kiesewetter H, Jung F, Hoffmann KH, Birk A, Muller A, Grutzne KI: Leg oedema protection from a buckwheat herb tea in patients with chronic venous insufficiency: a single-centre, randomised, double-blind, placebo-controlled clinical trial. Eur J Clin Pharmacol 1996;50:443-447.
[PubMed]
10.
Hu QH, Zhang X, Pan Y, Li YC, Kong LD: Allopurinol, quercetin and rutin ameliorate renal NLRP3 inflammasome activation and lipid accumulation in fructose-fed rats. Biochem Pharmacol 2012,84:113-125.
[PubMed]
11.
Zhu JX, Wang Y, Kong LD, Yang C, Zhang X: Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver. J Ethnopharmacol 2004;93:133-140.
[PubMed]
12.
Middleton E, Kandaswami C, Theoharides TC: The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharm Rev 2000;52:673-751.
[PubMed]
13.
Ohno I: Uricosuric agent. Nippon Rinsho 2008;66:743-747.
[PubMed]
14.
Eraly SA, Vallon V, Rieg T, Gangoiti JA, Wikoff WR, Siuzdak G, Barshop BA, Nigam SK: Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol Genomics 2008;33:180-192.
[PubMed]
15.
Dresser MJ, Leabman MK, Giacomini KM: Transporters involved in the elimination of drugs in the kidney: organic anion transporters and organic cation transporters. J Pharm Sci 2001;90:397-421.
[PubMed]
16.
Hu QH, Jiao RQ, Wang X, Lv YZ, Kong LD: Simiao pill ameliorates urate underexcretion and renal dysfunction in hyperuricemic mice. J Ethnopharmacol 2010;128:685-692
[PubMed]
17.
Brown CDA, Sayer R, Windass AS, Haslam IS, De Broe ME, D'Haese PC, Verhulst A: Characterisation of human tubular cell monolayers as a model of proximal tubular xenobiotic handling. Toxicol Appl Pharm 2008;233:428-438.
[PubMed]
18.
Korkmaz A, Kolankaya D: Protective effect of rutin on the ischemia/reperfusion induced damage in rat kidney. J Surg Res 2010;164:309-315.
[PubMed]
19.
Dahan K, Devuyst O, Smaers M, Vertommen D, Loute G, Poux JM, Viron B, Jacquot C, Gagnadoux MF, Chauveau D, Buchler M, Cochat P, Cosyns JP, Mougenot B, Rider MH, Antignac C, Verellen-Dumoulin C, Pirson Y: A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin. J Am Soc Nephrol 2003;14:2883-2893.
[PubMed]
20.
Carroll JJ, Coburn H, Douglass R, Babson AL: A simplified alkaline phosphotungstate assay for uric acid in serum. Clin Chem 1971;17:158-160.
[PubMed]
21.
Li JM, Zhang X, Wang X, Xie YC, Kong LD: Protective effects of cortex fraxini coumarines against oxonate-induced hyperuricemia and renal dysfunction in mice. Eur J Pharmacol 2011;666:196-204.
[PubMed]
22.
Hosoyamada M, Ichida K, Enomoto A, Hosoya T, Endou H: Function and localization of urate transporter 1 in mouse kidney. J Am Soc Nephrol 2004;15:261-268.
[PubMed]
23.
Wang Y, Zhu JX, Kong LD, Yang C, Cheng CH, Zhang X: Administration of procyanidins from grape seeds reduces serum uric acid levels and decreases hepatic xanthine dehydrogenase/oxidase activities in oxonate-treated mice. Basic Clin Pharmacol Toxicol 2004;94:232-237.
[PubMed]
24.
Huang J, Wang S, Zhu M, Chen J, Zhu X: Effects of genistein, apigenin, quercetin, rutin and astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice. Food Chem Toxicol 2011;49:1943-1947.
[PubMed]
25.
Deguchi T, Kouno Y, Terasaki T, Takadate A, Otagiri M: Differential contributions of rOat1 (Slc22a6) and rOat3 (Slc22a8) to the in vivo renal uptake of uremic toxins in rats. Pharm Res 2005;22:619-627.
[PubMed]
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