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https://www.readbyqxmd.com/read/28679589/insulin-stimulates-uric-acid-reabsorption-via-regulating-urate-transporter-1-and-atp-binding-cassette-sub-family-g-member-2
#1
Daigo Toyoki, Shigeru Shibata, Emiko Kuribayashi-Okuma, Ning Xu, Kenichi Ishizawa, Makoto Hosoyamada, Shunya Uchida
Accumulating data indicate that renal uric acid (UA) handling is altered in diabetes and by hypoglycemic agents. In addition, hyperinsulinemia is associated with hyperuricemia and hypouricosuria. However, the underlying mechanisms remain unclear. In this study, we aimed to investigate how diabetes and hypoglycemic agents alter the levels of renal UA transporters. In insulin-depleted diabetic rats with streptozotocin treatment, both UA excretion and fractional excretion of UA (FEUA) were increased, suggesting that tubular handling of UA is altered in this model...
July 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28624426/saponins-extracted-from-dioscorea-collettii-rhizomes-regulate-the-expression-of-urate-transporters-in-chronic-hyperuricemia-rats
#2
Liran Zhu, Yifan Dong, Sha Na, Ru Han, Chengyin Wei, Guangliang Chen
OBJECTIVE: The current study aimed to investigate whether the saponins, bioactive component of effects of D. collettii, could reduce the serum uric acid level in a hyperuricemic mouse via regulation of urate transporters. METHODS: Chronic hyperuricemia model was established by combine administration of adenine (100mg/kg) and ethambutol (250mg/kg). In the model group, the serum uric acid (SUA), urine uric acid (UUA) volume, and 24-h UUA values increased significantly, while the uric acid clearance rate (CUr) and creatinine clearance rate (CCr) values decreased...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28623927/caffeoylquinic-acid-derivatives-rich-extract-from-gnaphalium-pensylvanicum-willd-ameliorates-hyperuricemia-and-acute-gouty-arthritis-in-animal-model
#3
Yan Jiang, Yan Lin, Yi-Juan Hu, Xiao-Jun Song, Hong-Hua Pan, Hong-Jian Zhang
BACKGROUND: The Gnaphalium pensylvanicum willd. is used in China as a folk medicine to treat anti-inflammatory, cough and rheumatism arthritis. The aim of this study was to evaluate the potential of the extract of G. pensylvanicum to treat hyperuricemia and acute gouty arthritis in animal model. METHODS: G. pensylvanicum extract was evaluated in an experimental model with potassium oxonate (PO) induced hyperuricemia in mice which was used to evaluate anti-hyperuricemia activity and xanthine oxidase (XO) inhibition...
June 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28558868/anti-hyperuricemic-and-anti-inflammatory-actions-of-vaticaffinol-isolated-from-dipterocarpus-alatus-in-hyperuricemic-mice
#4
Yu-Sheng Chen, Chao-Jun Chen, Wei Yan, Hui-Ming Ge, Ling-Dong Kong
The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg(-1) potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg(-1) was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice...
May 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28499081/negative-correlation-between-serum-uric-acid-and-kidney-urat1-mrna-expression-caused-by-resveratrol-in-rats
#5
Cheng-Tse Lee, Li-Ching Chang, Ching-Wen Liu, Pei-Fung Wu
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...
May 12, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28425024/lesinurad-a-review-in-hyperuricaemia-of-gout
#6
Emma D Deeks
Lesinurad (Zurampic(®)) is an oral selective inhibitor of the URAT1 and OAT4 uric acid (UA) transporters of the kidney, via which it inhibits UA reabsorption and thus increases renal UA excretion and lowers serum UA (sUA) levels. Lesinurad 200 mg once daily is indicated for use in combination with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in adults with gout who have not achieved target sUA levels with an XOI alone. Approval was based on three 12-month phase 3 trials that evaluated lesinurad in combination with allopurinol in adults with gout inadequately responsive to allopurinol (CLEAR 1 and 2) and in combination with febuxostat in adults with tophaceous gout (CRYSTAL)...
April 19, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28386072/discovery-and-characterization-of-verinurad-a-potent-and-specific-inhibitor-of-urat1-for-the-treatment-of-hyperuricemia-and-gout
#7
Philip K Tan, Sha Liu, Esmir Gunic, Jeffrey N Miner
Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Two of these residues, Ser-35 and Phe-365, are also important for urate transport kinetics...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28357121/uricosuric-targets-of-tranilast
#8
Asim K Mandal, Adriana Mercado, Andria Foster, Kambiz Zandi-Nejad, David B Mount
Uric acid, generated from the metabolism of purines, has both proven and emerging roles in human disease. Serum uric acid in humans is determined by production and by the net balance of reabsorption and secretion in kidney and intestine. In the human kidney, epithelial reabsorption dominates over secretion, such that in normal subjects there is at least 90% net reabsorption of filtered urate resulting in a fractional excretion of <10%. Tranilast, an anti-inflammatory drug with pleiotropic effects, has a marked hypouricemic, uricosuric effect in humans...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28340987/discovery-of-novel-curcumin-derivatives-targeting-xanthine-oxidase-and-urate-transporter-1-as-anti-hyperuricemic-agents
#9
Gui-Zhen Ao, Meng-Ze Zhou, Yu-Yao Li, Si-Ning Li, Hua-Nian Wang, Qian-Wen Wan, Huan-Qiu Li, Qing-Hua Hu
A series of curcumin derivatives as potent dual inhibitors of xanthine oxidase (XOD) and urate transporter 1 (URAT1) was discovered as anti-hyperuricemic agents. These compounds proved efficient effects on anti-hyperuricemic activity and uricosuric activity in vivo. More importantly, some of them exhibited proved efficient effects on inhibiting XOD activity and suppressing uptake of uric acid via URAT1 in vitro. Especially, the treatment of 4d was demonstrated to improve uric acid over-production and under-excretion in oxonate-induced hyperuricemic mice through regulating XOD activity and URAT1 expression...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28258276/gypenosides-inhibits-xanthine-oxidoreductase-and-ameliorates-urate-excretion-in-hyperuricemic-rats-induced-by-high-cholesterol-and-high-fat-food-lipid-emulsion
#10
Minxia Pang, Yingying Fang, Suhong Chen, Xuexin Zhu, Chaowen Shan, Jie Su, Jingjing Yu, Bo Li, Yao Yang, Bo Chen, Kailun Liang, Huiming Hu, Guiyuan Lv
BACKGROUND The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. MATERIAL AND METHODS Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE...
March 4, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28163535/lesinurad-a-significant-advancement-or-just-another-addition-to-existing-therapies-of-gout
#11
REVIEW
Ajay Gupta, Pramod Kumar Sharma, Arup Kumar Misra, Surjit Singh
Gout is a metabolic disorder that usually presents as recurrent episodes of acute arthritis due to deposition of crystals in joints and cartilages. Despite the availability of several drugs for gout, its management is still less than adequate. There is always a search for newer, safer, and more potent urate-lowering therapies for treating patients inadequately controlled with available drugs. Lesinurad in combination with a xanthine oxidase inhibitor provides an effective mode of therapy in the management of hyperuricemia associated with gout...
October 2016: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28039413/urat1-inhibition-by-alpk1-is-associated-with-uric-acid-homeostasis
#12
Tzer-Min Kuo, Chung-Ming Huang, Hung-Pin Tu, Albert Min-Shan Ko, Shu-Jung Wang, Chi-Pin Lee, Ying-Chin Ko
Objective.: The aim of this study was to identify a protein for urate transporter 1 (URAT1) regulation. Methods.: The clinical dataset consisted of 492 case-control samples of Han Chinese (104 gout and 388 controls). Three alpha kinase 1 ( ALPK1 ) and SLC22A12 loci associated with high gout risk and uric acid levels were genotyped. The overexpression of ALPK1 on URAT1 protein expression was evaluated in vivo in h ALPK1 transgenic mice. The in vitro protein levels of ALPK1 and URAT1 in ALPK1 small interfering RNA-transfected human kidney-2 cells with MSU crystal stimulation were examined...
April 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/27960017/-recent-advances-in-urate-metabolism
#13
Giulia Mori, Riccardo Percudani
In the last fifteen years, genomics and other -omics sciences have revolutionized our understanding of biological processes at the molecular level. An illustrative example is urate metabolism. Before the publication of the complete human genome, in 2003 it was believed that a single enzyme (urate oxidase) was responsible for uricolysis that is the conversion of urate into the more soluble allantoin. Now we know with great detail that this process requires the consecutive action of three enzymes that have been lost by gene inactivation in our hominoid ancestor...
2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/27955673/immunohistochemical-and-in-situ-hybridization-study-of-urate-transporters-glut9-uratv1-abcg2-and-urat1-in-the-murine-brain
#14
Naoko H Tomioka, Yoshifuru Tamura, Tappei Takada, Shigeru Shibata, Hiroshi Suzuki, Shunya Uchida, Makoto Hosoyamada
BACKGROUND: Uric acid (UA) is known to exert neuroprotective effects in the brain. However, the mechanism of UA regulation in the brain is not well characterized. In our previous study, we described that the mouse urate transporter URAT1 is localized to the cilia and apical surface of ventricular ependymal cells. To further strengthen the hypothesis that UA is transported transcellularly at the ependymal cells, we aimed to assess the distribution of other UA transporters in the murine brain...
December 12, 2016: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/27951420/-e-2-4-bromophenyl-1-2-4-dihydroxyphenyl-ethanone-oxime-is-a-potential-therapeutic-agent-for-treatment-of-hyperuricemia-through-its-dual-inhibitory-effects-on-xod-and-urat1
#15
Qinghua Hu, Mengze Zhou, Haoran Zhu, Guo Lu, Dongsen Zheng, Huanqiu Li, Kun Hao
Hyperuricemia is a kind of metabolic disease resulted from imbalance between urate production and excretion. Xanthine oxidase (XOD) or renal urate transporter 1 (URAT1) inhibitors have been applied for hyperuricemia treatment in clinic, but available drugs could not simultaneously target XOD and URAT1 and had various adverse effects. (E)-2-(4-bromophenyl)-1-(2, 4-dihydroxyphenyl)ethanone oxime (BDEO), as a deoxybenzoins oxime analog, was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic activity, which was expected to be dual inhibitor of XOD and URAT1...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27906637/prevalence-of-urat1-allelic-variants-in-the-roma-population
#16
Blanka Stiburkova, Dana Gabrikova, Pavel Čepek, Pavel Šimek, Pavol Kristian, Elizabeth Cordoba-Lanus, Felix Claverie-Martin
The Roma represents a transnational ethnic group, with a current European population of 8-10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906636/urat1-uox-double-knockout-mice-are-experimental-animal-models-of-renal-hypouricemia-and-exercise-induced-acute-kidney-injury
#17
Makoto Hosoyamada, Yu Tsurumi, Hidenori Hirano, Naoko H Tomioka, Yuko Sekine, Takayuki Morisaki, Shunya Uchida
Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI)...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906625/uric-acid-metabolism-of-kidney-and-intestine-in-a-rat-model-of-chronic-kidney-disease
#18
Michito Nagura, Yoshifuru Tamura, Takanori Kumagai, Makoto Hosoyamada, Shunya Uchida
Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27854343/discovery-of-a-flexible-triazolylbutanoic-acid-as-a-highly-potent-uric-acid-transporter-1-urat1-inhibitor
#19
He Tian, Wei Liu, Zhixing Zhou, Qian Shang, Yuqiang Liu, Yafei Xie, Changying Liu, Weiren Xu, Lida Tang, Jianwu Wang, Guilong Zhao
In order to systematically explore and understand the structure-activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH₂, 18 compounds (1a-1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC50 = 0.23 μM against human URAT1 for 1q vs 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity...
November 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27780716/a-novel-compound-heterozygous-mutation-in-the-slc22a12-urat1-gene-in-a-japanese-patient-associated-with-renal-hypouricemia
#20
Kyoko Fujita, Kimiyoshi Ichida
A novel compound heterozygous mutation, including c.935_997delinsTGG, in exons 5/6 of SLC22A12 (URAT1) was identified in a patient with renal hypouricemia. This case expands the molecular mechanisms of renal hypouricemia, and suggests a potential relationship with exercise-induced renal failure.
December 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
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