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2000
Volume 32, Issue 14
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Hyperuricemia (HUA) is a disease characterized by excessive uric acid production and/or insufficient uric acid excretion caused by abnormal purine metabolism in the human body. Uric acid deposition caused by hyperuricemia can cause complications, such as kidney damage. The current therapeutic drugs for HUA are not very targeted and usually have specific toxic side effects.

Objectives

This study aimed to synthesize a compound using rhein and praseodymium, which can effectively help hyperuricemia patients with kidney injury to excrete uric acid through the intestine and preliminarily explore its intestinal excretion mechanism.

Methods

The natural active ingredient rhein and rare earth metal praseodymium were used to synthesize Rh-Pr. The possible chemical structure of Rh-Pr was deduced by UV, IR, 1H-NMR, conductivity method, and thermogravity analysis. Adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) were administered by gavage for three weeks to establish the hyperuricemia rat model of renal injury. Serum uric acid (UA), creatinine (Cr), urea nitrogen (BUN), and uric acid concentration in urine and feces were detected by biochemical methods. The protein expression levels of GLUT9, ABCG2, and MRP4 in the jejunum, ileum, and colon of rats were detected by Western blotting.

Results

According to the characterization, the chemical composition formula of the complex is Pr(CHO)·2HO. , activity tests showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, upregulate the expression of ABCG2 protein in the jejunum and ileum, down-regulate the expression of GLUT9 protein in the ileum and colon, and also had a good recovery effect on serum uric acid, creatinine, and urea nitrogen levels.

Conclusion

Rh-Pr is different from other drugs in that it promotes intestinal uric acid excretion and has a renal recovery effect. It reduces the patient's kidney burden and is significant for hyperuricemia patients with kidney injury.

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References

  1. JohnsonR.J. BakrisG.L. BorghiC. ChoncholM.B. FeldmanD. LanaspaM.A. MerrimanT.R. MoeO.W. MountD.B. Sanchez LozadaL.G. StahlE. WeinerD.E. ChertowG.M. Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: Report of a scientific workshop organized by the national kidney foundation.Am. J. Kidney Dis.201871685186510.1053/j.ajkd.2017.12.009 29496260
     [Google Scholar]
  2. KimH. KimS. ChoiA.R. KimS. ChoiH.Y. KimH.J. ParkH.C. Asymptomatic hyperuricemia is independently associated with coronary artery calcification in the absence of overt coronary artery disease.Medicine20179614e656510.1097/MD.0000000000006565 28383435
     [Google Scholar]
  3. ChoiH.K. A prescription for lifestyle change in patients with hyperuricemia and gout.Curr. Opin. Rheumatol.201022216517210.1097/BOR.0b013e328335ef38 20035225
     [Google Scholar]
  4. Chinese multidisciplinary expert consensus on the diagnosis and treatment of hyperuricemia and related diseases.Chin. Med. J.2017130202473248810.4103/0366‑6999.216416 29052570
     [Google Scholar]
  5. ShirakabeA. OkazakiH. MatsushitaM. ShibataY. GodaH. UchiyamaS. TaniK. KiuchiK. KobayashiN. HataN. AsaiK. ShimizuW. Hyperuricemia complicated with acute kidney injury is associated with adverse outcomes in patients with severely decompensated acute heart failure.Int. J. Cardiol. Heart Vasc.20192310034510.1016/j.ijcha.2019.03.005 31321285
     [Google Scholar]
  6. ReesF. HuiM. DohertyM. Optimizing current treatment of gout.Nat. Rev. Rheumatol.201410527128310.1038/nrrheum.2014.32 24614592
     [Google Scholar]
  7. SattuiS.E. GaffoA.L. Treatment of hyperuricemia in gout: Current therapeutic options, latest developments and clinical implications.Ther. Adv. Musculoskelet. Dis.20168414515910.1177/1759720X16646703 27493693
     [Google Scholar]
  8. ZhangS.Z. SuN. XuT. Meta analysis of cardiovascular adverse events and mortality risk in patients with gout treated with non bupropion compared to allopurinol.Chin. Pharm. Hos. J.20214102177182
     [Google Scholar]
  9. FelserA. LindingerP.W. SchnellD. KratschmarD.V. OdermattA. MiesS. JenöP. KrähenbühlS. Hepatocellular toxicity of benzbromarone: Effects on mitochondrial function and structure.Toxicology201432413614610.1016/j.tox.2014.08.002 25108121
     [Google Scholar]
  10. LiuY.C. LiY. ZhangG. Analysis of adverse reactions/events of benzbromarone in 18 cases.Zhongguo Yiyuan Yaoxue Zazhi20163606507510
     [Google Scholar]
  11. FinchA. Kubler, The management of gout.Aust. Prescr.201639411912210.18773/austprescr.2016.047 27756973
     [Google Scholar]
  12. TongY. ChenD.X. LiY. WangX.Q. YuX.F. LiuY.R. ChengS.J. LiY.P. WenH.L. ChengZ.C. LiJ.X. Clinical study on the treatment of acute gouty arthritis with Bi Ning Tang.J. Tradit. Chin. Med.20164436466
     [Google Scholar]
  13. ZhangX.X. SunW.F. XuW. Effects of xiezhuo chubi recipe on uric acid and urat1 in hyperuricemic mice. Chinese.J. Exp. Formul.2012182144147
     [Google Scholar]
  14. LiuY.W. SunW.F. ZhangX.X. LiJ. ZhangH.H. Compound Tufuling Granules (复方土茯苓颗粒) regulate glucose transporter 9 expression in kidney to influence serum uric acid level in hyperuricemia mice.Chin. J. Integr. Med.2015211182382910.1007/s11655‑015‑2052‑2 25864117
     [Google Scholar]
  15. WangG.Q. HuD. QingY.Y. Tiandan Jiangya Recipe in the treatment of 30 cases of hypertension with hyperuricemia and hyperactivity of liver yang.Hunan J. Tradit. Chin. Med.20213712810
     [Google Scholar]
  16. LiT. CuiX.F. ZhangY.Y. 45 cases of hyperuricemia treated with modified simiao powder.J. Pract. Tradit. Chin. Med.2021370711231124
     [Google Scholar]
  17. LipkowitzM.S. Leal-PintoE. CohenB.E. AbramsonR.G. Galectin 9 is the sugar-regulated urate transporter/channel UAT.Glycoconj. J.2002197-949149810.1023/B:GLYC.0000014078.65610.2f 14758072
     [Google Scholar]
  18. BhatnagarV. RichardE.L. WuW. NievergeltC.M. LipkowitzM.S. JeffJ. MaihoferA.X. NigamS.K. Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: Potential role of remote sensing and signaling.Clin. Kidney J.20169344445310.1093/ckj/sfw010 27274832
     [Google Scholar]
  19. Van AubelR.A.M.H. SmeetsP.H.E. van den HeuvelJ.J.M.W. RusselF.G.M. Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites.Am. J. Physiol. Renal Physiol.20052882F327F33310.1152/ajprenal.00133.2004 15454390
     [Google Scholar]
  20. DehghanA. KöttgenA. YangQ. HwangS.J. KaoW.H.L. RivadeneiraF. BoerwinkleE. LevyD. HofmanA. AstorB.C. BenjaminE.J. van DuijnC.M. WittemanJ.C. CoreshJ. FoxC.S. Association of three genetic loci with uric acid concentration and risk of gout: A genome-wide association study.Lancet200837296541953196110.1016/S0140‑6736(08)61343‑4 18834626
     [Google Scholar]
  21. HosomiA. NakanishiT. FujitaT. TamaiI. Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2.PLoS One201272e3045610.1371/journal.pone.0030456 22348008
     [Google Scholar]
  22. IharadaM. MiyajiT. FujimotoT. HiasaM. AnzaiN. OmoteH. MoriyamaY. Type 1 sodium-dependent phosphate transporter (SLC17A1 Protein) is a Cl(-)-dependent urate exporter.J. Biol. Chem.201028534261072611310.1074/jbc.M110.122721 20566650
     [Google Scholar]
  23. KolzM. JohnsonT. SannaS. TeumerA. VitartV. PerolaM. ManginoM. AlbrechtE. WallaceC. FarrallM. JohanssonÅ. NyholtD.R. AulchenkoY. BeckmannJ.S. BergmannS. BochudM. BrownM. CampbellH. ConnellJ. DominiczakA. HomuthG. LaminaC. McCarthyM.I. MeitingerT. MooserV. MunroeP. NauckM. PedenJ. ProkischH. SaloP. SalomaaV. SamaniN.J. SchlessingerD. UdaM. VölkerU. WaeberG. WaterworthD. Wang-SattlerR. WrightA.F. AdamskiJ. WhitfieldJ.B. GyllenstenU. WilsonJ.F. RudanI. PramstallerP. WatkinsH. DoeringA. WichmannH.E. SpectorT.D. PeltonenL. VölzkeH. NagarajaR. VollenweiderP. CaulfieldM. IlligT. GiegerC. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations.PLoS Genet.200956e100050410.1371/journal.pgen.1000504 19503597
     [Google Scholar]
  24. JutabhaP. AnzaiN. IchidaK. KimuraT. KitamuraK. HisatomeI. EndouH. SakuraiH. Functional characterization of a novel urate efflux transporter URATv1 (SLC2A9) and its relation to renal hypouricemia.FASEB J.200923S160310.1096/fasebj.23.1_supplement.603.1
     [Google Scholar]
  25. AnzaiN. IchidaK. JutabhaP. KimuraT. BabuE. JinC.J. SrivastavaS. KitamuraK. HisatomeI. EndouH. SakuraiH. Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans.J. Biol. Chem.200828340268342683810.1074/jbc.C800156200 18701466
     [Google Scholar]
  26. LiuS. YuanY. ZhouY. ZhaoM. ChenY. ChengJ. LuY. LiuJ. Phloretin attenuates hyperuricemia‐induced endothelial dysfunction through co‐inhibiting inflammation and GLUT 9‐mediated uric acid uptake.J. Cell. Mol. Med.201721102553256210.1111/jcmm.13176 28402018
     [Google Scholar]
  27. XuX. LiC. ZhouP. JiangT. Uric acid transporters hiding in the intestine.Pharm. Biol.201654123151315510.1080/13880209.2016.1195847 27563755
     [Google Scholar]
  28. GopalE. FeiY.J. SugawaraM. MiyauchiS. ZhuangL. MartinP. SmithS.B. PrasadP.D. GanapathyV. Expression of slc5a8 in kidney and its role in Na(+)-coupled transport of lactate.J. Biol. Chem.200427943445224453210.1074/jbc.M405365200 15322102
     [Google Scholar]
  29. HosoyamadaM. TakiueY. ShibasakiT. SaitoH. The effect of testosterone upon the urate reabsorptive transport system in mouse kidney.Nucleosides Nucleotides Nucleic Acids201029757457910.1080/15257770.2010.494651 20589576
     [Google Scholar]
  30. NakayamaA. MatsuoH. TakadaT. ABCG2 is a high-capacity urate transporter and its genetic impairment increases serum uric acidlevels in humans.Nucleos Nucleot Nucl.20113010911097
     [Google Scholar]
  31. IchidaK. MatsuoH. TakadaT. NakayamaA. MurakamiK. ShimizuT. YamanashiY. KasugaH. NakashimaH. NakamuraT. TakadaY. KawamuraY. InoueH. OkadaC. UtsumiY. IkebuchiY. ItoK. NakamuraM. ShinoharaY. HosoyamadaM. SakuraiY. ShinomiyaN. HosoyaT. SuzukiH. Decreased extra-renal urate excretion is a common cause of hyperuricemia.Nat. Commun.20123176410.1038/ncomms1756 22473008
     [Google Scholar]
  32. PhayJ.E. HussainH.B. MoleyJ.F. Cloning and expression analysis of a novel member of the facilitative glucose transporter family, SLC2A9(GLUT9).Genomics2000662217220
     [Google Scholar]
  33. BibertS. HessS.K. FirsovD. Mouse GLUT9: Evidences for a urate uniporter.Am. J. Physiol. Renal Physiol.20092973F612F61910.1152/ajprenal.00139.2009
     [Google Scholar]
  34. MandalA.K. MountD.B. The molecular physiology of uric acid homeostasis.Annu. Rev. Physiol.20157732334510.1146/annurev‑physiol‑021113‑170343
     [Google Scholar]
  35. PreitnerF. BonnyO. LaverrièreA. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and uratenephropathy.Proc. Natl. Acad. Sci.20091061550115506
     [Google Scholar]
  36. MobasheriaA. DobsonaH. MasonaS.L. Expression of the GLUT1 and GLUT9 facilitative glucose transporters in embryonic chondroblasts and mature chondrocytes in ovine articular cartilage.Cell Biol. Int.200529424926010.1016/j.cellbi.2004.11.024
     [Google Scholar]
  37. DeBoschB.J. KluthO. FujiwaraH. SchürmannA. MoleyK. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9.Nat. Commun.201451464210.1038/ncomms5642 25100214
     [Google Scholar]
  38. MengZ. YanY. TangZ. GuoC. LiN. HuangW. DingG. WangZ. XiaoW. YangZ. Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice.Planta Med.201581427928510.1055/s‑0034‑1396241 25760382
     [Google Scholar]
  39. WuJ. WeiZ. ChengP. QianC. XuF. YangY. WangA. ChenW. SunZ. LuY. Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis.Theranostics20201023106651067910.7150/thno.43528 32929373
     [Google Scholar]
  40. WanitschkeR.W. KarbachU. Influence of rhein on rat colonic Na+, K+-ATPase and permeability in vitro.Pharmacology19883619810310.1159/000138427 2835785
     [Google Scholar]
  41. ZhangL. ChangJ. ZhangB. LiuX. LiuP. XueH. LiuL. FuQ. ZhuM. LiuC. The pharmacokinetic study on the mechanism of toxicity attenuation of rhubarb total free anthraquinone oral colon-specific drug delivery system.Fitoterapia2015104869610.1016/j.fitote.2015.05.018 26036751
     [Google Scholar]
  42. LiY.H. LuX.Y. LiuX. LiuY. Research advances in coordination chemistry of traditional Chinese medicine.Zhongguo Zhongyao Zazhi2006311613091313 17061546
     [Google Scholar]
  43. ChenY. ZouJ. SunH. QinJ. YangJ. Metals in traditional Chinese medicinal materials (TCMM): A systematic review.Ecotoxicol. Environ. Saf.202120711131110.1016/j.ecoenv.2020.111311 32947212
     [Google Scholar]
  44. MisraS.N. GagnaniM.A. M, I.D.; Shukla, R.S. Biological and clinical aspects of Lanthanide coordination compounds.Bioinorg. Chem. Appl.200423-415519210.1155/S1565363304000111 18365075
     [Google Scholar]
  45. YangL. WangB. TanJ. ZhuL. The DNA-binding and bioactivity of rare earth metal complexes.Mini Rev. Med. Chem.201313101487150010.2174/1389557511313100009 24568297
     [Google Scholar]
  46. RenQ. X. ShangZ. H. GuoL. Preparation of N, Ocarboxymethyl chitosan and praseodymium complexes.20103210889891
     [Google Scholar]
  47. ZhangM.L. ZhengY.J. Synthesis and fluorescence properties of rare earth pr (III) complexes.Chem. Adhesion.201840028992
     [Google Scholar]
  48. LiZ. WangY. F. CaoJ. Synthesis and luminescent properties of a novel praseodymium (Ⅲ) Schiff base complex.New J. Chem.20164411134136+139
     [Google Scholar]
  49. AndiappanK. SanmugamA. DeivanayagamE. KaruppasamyK. KimH.S. VikramanD. Schiff base rare earth metal complexes: Studies on functional, optical and thermal properties and assessment of antibacterial activity.Int. J. Biol. Macromol.201912440341010.1016/j.ijbiomac.2018.11.251 30500493
     [Google Scholar]
  50. ZhangX. CuiN. HouJ.L. Establishment of a rat model of acute chronic hyperuricemia.World Chinese Medicine202316
     [Google Scholar]
  51. ChenJ.X. LiuG. LiuL. Experimental study on five methods for preparing hyperuricemia rat models. J Guang.Univer. Trad. Chinese Med.2021381124562461
     [Google Scholar]
  52. XiongX.M. QuZ.Q. JiaX.L. Establishment of a rat model of hyperuricemia with renal damage. Chinese.J. Comp. Med.2005154206209
     [Google Scholar]
  53. YuM. Clinical analysis of 20 cases of Hyperuricemia treated with medicinal charcoal.J. Huazhong Univ. Sci. Technol.20132703216217
     [Google Scholar]
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Effect and Mechanism of Rhein-praseodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia
Curr. Med. Chem. 32, 2838 (2025); https://doi.org/10.2174/0109298673268642231214061615
/content/journals/cmc/10.2174/0109298673268642231214061615
/content/journals/cmc/10.2174/0109298673268642231214061615
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  • Article Type:     Research Article
Keyword(s): ABCG2; GLUT9; Hyperuricemia; metal complexes; MRP4; rhein

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