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Allopurinol decreases serum uric acid level and intestinal glucose transporter-5 expression in rats with fructose-induced hyperuricemia

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Abstract

Background

High fructose consumption is considered to be related to the increasing prevalence of hyperuricemia (HUA). Glucose transporters (GLUT) 2 and 5 are crucial for fructose absorption and transporter. Effects of anti-HUA drugs, allopurinol (API) and benzbromarone (BBR), on expressions of GLUT5 and GLUT2 are not evaluated.

Method

Wistar rats were given 10% fructose in drinking water for 60 days to induce HUA, and 5 mg/kg API and 10 mg/kg BBR were intragastricly treated for 30 days. Serum level of uric acid and xanthine oxidase (XOD) activity in liver were determined. Expressions of GLUT2 and GLUT5 in intestine were analyzed by immunohistochemistry staining assay and Western blot assay.

Results

Treatment with API or BBR significantly decreased the serum level of uric acid in HUA rats induced by fructose. Meanwhile, API treatment significantly reduced the XOD activity in liver and GLUT5 expression in intestine. However, BBR treatment did not show inhibitory effects on hepatic XOD activity and intestinal GLUT5 expression. In addition, treatment with API or BBR did not show any effect on GLUT2 expression in intestine.

Conclusion

API decreases serum level of uric acid in fructose-induced HUA rats. The mechanisms are associated with suppressing XOD activity in liver to reduce uric acid production, and inhibiting GLUT5 expression in intestine to reduce fructose absorption.

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References

  1. Wang J, Chen RP, Lei L, Song QQ, Zhang RY, Li YB, et al. Prevalence and determinants of hyperuricemia in type 2 diabetes mellitus patients with central obesity in Guangdong Province in China. Asia Pac J Clin Nutr 2013;22:590–8.

    PubMed  Google Scholar 

  2. Hosoya T, Kimura K, Itoh S, Inaba M, Uchida S, Tomino Y, et al. The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study. Trials 2014;15:26.

    Article  Google Scholar 

  3. Krishnan E, Pandya BJ, Chung L, Dabbous O. Hyperuricemia and the risk for subclinical coronary atherosclerosis — data from a prospective observational cohort study. Arthritis Res Ther 2011;13:R66.

    Article  Google Scholar 

  4. Stamp LK, Chapman PT. Urate-lowering therapy: current options and future prospects for elderly patients with gout. Drugs Aging 2014;31:777–86.

    Article  CAS  Google Scholar 

  5. Gosling AL, Matisoo-Smith E, Merriman TR. Hyperuricaemia in the Pacific: why the elevated serum urate levels? Rheumatol Int 2014;34(6):743–57.

    Article  CAS  Google Scholar 

  6. Choi JW, Ford ES, Gao X, Choi HK. Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2008;59:109–16.

    Article  CAS  Google Scholar 

  7. Hanover LM, White JS. Manufacturing, composition, and applications of fructose. Am J Clin Nutr 1993;58:724S–32S.

    Article  CAS  Google Scholar 

  8. Fox IH, Kelley WN. Studies on the mechanism of fructose-induced hyperuricemia in man. Metabolism 1972;21:713–21.

    Article  CAS  Google Scholar 

  9. Barone S, Fussell SL, Singh AK, Lucas F, Xu J, Kim C, et al. Slc2a5 (Glut5) is essential for the absorption of fructose in the intestine and generation of fructose-induced hypertension. J Biol Chem 2009;284:5056–66.

    Article  CAS  Google Scholar 

  10. Stumpel F, Burcelin R, Jungermann K, Thorens B. Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum. Proc Natl Acad Sci U S A 2001;98:11330–35.

    Article  CAS  Google Scholar 

  11. Davidson NO, Hausman AM, Ifkovits CA, Buse JB, Gould GW, Burant CF, et al. Human intestinal glucose transporter expression and localization of GLUT5. Am J Physiol 1992;262:C795–800.

    Article  CAS  Google Scholar 

  12. Jiang L, Ferraris RP. Developmental reprogramming of rat GLUT-5 requires de novo mRNA and protein synthesis. Am J Physiol Gastrointest Liver Physiol 2001;280:G113–20.

    Article  CAS  Google Scholar 

  13. Hu QH, Wang C, Li JM, Zhang DM, Kong LD. Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement. Am J Physiol Renal Physiol 2009;297:F1080–91.

    Article  CAS  Google Scholar 

  14. Chen CC, Hsu YJ, Lee TM. Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia. Am J Physiol Heart Circ Physiol 2011;301:H1107–17.

    Article  CAS  Google Scholar 

  15. Wallace KL, Riedel AA, Joseph-Ridge N, Wortmann R. Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population. J Rheumatol 2004;31:1582–7.

    PubMed  Google Scholar 

  16. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093–103.

    Article  CAS  Google Scholar 

  17. Rho YH, Zhu Y, Choi HK. The epidemiology of uric acid and fructose. Semin Nephrol 2011;31:410–9.

    Article  CAS  Google Scholar 

  18. Hallfrisch J. Metabolic effects of dietary fructose. FASEB J 1990;4(9):2652–60.

    Article  CAS  Google Scholar 

  19. Chen L, Lan Z, Zhou Y, Li F, Zhang X, Zhang C, et al. Astilbin attenuates hyperuricemia and ameliorates nephropathy in fructose-induced hyperuricemic rats. Planta Med 2011;77:1769–73.

    Article  CAS  Google Scholar 

  20. Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, et al. A causal role for uric acid in fructose-induced metabolic syndrome. Am J Physiol Renal Physiol 2006;290:F625–31.

    Article  CAS  Google Scholar 

  21. George J, Struthers AD. Role of urate, xanthine oxidase and the effects of allopurinol in vascular oxidative stress. Vasc Health Risk Manag 2009;5: 265–72.

    Article  CAS  Google Scholar 

  22. Stamp LK, Chapman PT. Urate-lowering therapy: current options and future prospects for elderly patients with gout. Drugs Aging 2014;31:777–86.

    Article  CAS  Google Scholar 

  23. Stevenson M, Pandor A. Febuxostat for the management of hyperuricaemia in patients with gout: a NICE single technology appraisal. Pharmacoeconomics 2011;29:133–40.

    Article  Google Scholar 

  24. Cheeseman CI. GLUT2 is the transporter for fructose across the rat intestinal basolateral membrane. Gastroenterology 1993;105:1050–6.

    Article  CAS  Google Scholar 

  25. Thorens B, Mueckler M. Glucose transporters in the 21st Century. Am J Physiol Endocrinol Metab 2010;298:E141–5.

    Article  CAS  Google Scholar 

  26. Miyamoto K, Hase K, Taketani Y, Minami H, Oka T, Nakabou Y, et al. Diabetes and glucose transporter gene expression in rat small intestine. Biochem Biophys Res Commun 1991;181:1110–7.

    Article  CAS  Google Scholar 

  27. Cui XL, Jiang L, Ferraris RP. Regulation of rat intestinal GLUT2 mRNA abundance by luminal and systemic factors. Biochim Biophys Acta 2003;1612: 178–85.

    Article  CAS  Google Scholar 

  28. Castello A, Guma A, Sevilla L, Furriols M, Testar X, Palacin M, et al. Regulation of GLUT5 gene expression in rat intestinal mucosa: regional distribution, circadian rhythm, perinatal development and effect of diabetes. Biochem J 1995;309:271–7.

    Article  CAS  Google Scholar 

  29. Mahraoui L, Takeda J, Mesonero J, Chantret I, Dussaulx E, Bell GI, et al. Regulation of expression of the human fructose transporter (GLUT5) by cyclic AMP. Biochem J 1994;301:169–75.

    Article  CAS  Google Scholar 

  30. Garcia-Herrera J, Navarro MA, Marca MC, de la Osada J, Rodriguez-Yoldi MJ. The effect of tumor necrosis factor-alpha on d-fructose intestinal transport in rabbits. Cytokine 2004;25:21–30.

    Article  CAS  Google Scholar 

  31. Miyamoto K, Hase K, Takagi T, Fujii T, Taketani Y, Minami H, et al. Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars. Biochem J 1993;295:211–5.

    Article  CAS  Google Scholar 

  32. Zhou JQ, Qiu T, Zhang L, Chen ZB, Wang ZS, Ma XX, et al. Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model. Acta Cir Bras 2016;31:176–82.

    Article  Google Scholar 

  33. Agarwal V, Hans N, Messerli FH. Effect of allopurinol on blood pressure: a systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2013;15: 435–42.

    Article  CAS  Google Scholar 

  34. Sanchis-Gomar F, Bonaguri C, Aloe R, Pareja-Galeano H, Martinez-Bello V, Gomez-Cabrera MC, et al. Effects of acute exercise and xanthine oxidase inhibition on novel cardiovascular biomarkers. Transl Res 2013;162:102–9.

    Article  CAS  Google Scholar 

  35. Sanchis-Gomar F, Bonaguri C, Pareja-Galeano H, Gomez-Cabrera MC, Candel J, Viña J, et al. Effects of acute exercise and allopurinol administration on soluble urokinase plasminogen activator receptor (suPAR). Clin Lab 2013;59:207–10.

    Article  CAS  Google Scholar 

  36. Sanchis-Gomar F, Pareja-Galeano H, Gomez-Cabrera MC, Candel J, Lippi G, Salvagno GL, Mann GE, et al. Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players. Scand J Med Sci Sports 2015;25:e110–5.

    Article  CAS  Google Scholar 

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Correspondence to Gang Chen.

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Chen, G., Jia, P. Allopurinol decreases serum uric acid level and intestinal glucose transporter-5 expression in rats with fructose-induced hyperuricemia. Pharmacol. Rep 68, 782–786 (2016). https://doi.org/10.1016/j.pharep.2016.04.014

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  • DOI: https://doi.org/10.1016/j.pharep.2016.04.014

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