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https://www.readbyqxmd.com/read/29233733/regulation-mechanism-of-dioscin-on-uric-acid-excretion
#1
Yi Zhang, Lijun Jin, Jinchang Liu, Wei Wang, Haiyang Yu, Jian Li, Qian Chen, Tao Wang
ETHNOPHARMACOLOGY RELEVANCE: Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels. AIM OF THE STUDY: The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity...
December 9, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29145399/point-mutation-in-d8c-domain-of-tamm-horsfall-protein-uromodulin-in-transgenic-mice-causes-progressive-renal-damage-and-hyperuricemia
#2
Lijie Ma, Yan Liu, Nichole K Landry, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance...
2017: PloS One
https://www.readbyqxmd.com/read/29126251/evidence-for-a-role-of-pdz-domain-containing-proteins-to-mediate-hypophosphatemia-in-calcium-stone-formers
#3
Kristin J Bergsland, Fredric L Coe, Joan H Parks, John R Asplin, Elaine M Worcester
Background: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP...
November 6, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29103339/lesinurad-for-the-treatment-of-hyperuricaemia-in-people-with-gout
#4
Philip C Robinson, Nicola Dalbeth
Gout is a common form of inflammatory arthritis caused by deposition of monosodium urate crystals. The central strategy for effective long-term management of gout is serum urate lowering. Current urate-lowering drugs include both xanthine oxidase inhibitors and uricosuric agents. Lesinurad is a URAT1 inhibitor that selectively inhibits urate rebsorption at the proximal renal tubule. Lesinurad 200mg daily in combination with a xanthine oxidase is approved for urate-lowering therapy in patients with gout. Areas covered: The published literature was searched using Pubmed and additional information was obtained from publically available regulatory documents...
November 13, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29091862/the-anti-hyperuricemic-effect-of-epigallocatechin-3-gallate-egcg-on-hyperuricemic-mice
#5
Chuang Zhu, Yan Xu, Zeng-Hui Liu, Xiao-Chun Wan, Da-Xiang Li, Ling-Ling Tai
Epigallocatechin-3-gallate (EGCG), a major constituent of green tea catechin, has been used for antioxidant. This study aimed to evaluate the antihyperuricemic activity of EGCG on hyperuricemic mice. We demonstrated that serum uric acid (UA) level was decreased significantly with dose-dependence by EGCG treated with 10, 20, and 50mg/kg. Compared with the model, data on blood urea nitrogen (BUN) supported that there was significance with high dose of EGCG (50mg/kg). Levels of serum creatinine (Cr) in each EGCG-treated group were decreased but not significant; the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) in high dose groups' EGCG were notably lower than those of model group...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29057475/erding-formula-in-hyperuricaemia-treatment-unfolding-traditional-chinese-herbal-compatibility-using-modern-pharmaceutical-approaches
#6
Jieyu Zuo, Hongming He, Zhengyun Zuo, Nádia Bou-Chacra, Raimar Löbenberg
OBJECTIVES: Traditional Chinese herbal formulas are difficult to be understood because of complex compositions and specific therapeutic principles. To better understand herbal compatibility in Traditional Chinese medicine (TCM), this study was conducted to investigate the effects of a Chinese pharmacopoeia-listed formula, Erding Formula (EF) and its constituent herbs for a new indication, hyperuricaemia. METHODS: A hypoxanthine and potassium oxonate-induced hyperuricemic mouse model, a xylene-induced inflammatory mouse model and an acetic acid-induced pain model were used to test the effects of EF and its constituent herbs...
October 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29035321/a-novel-multi-epitope-vaccine-based-on-urate-transporter-1-alleviates-streptozotocin-induced-diabetes-by-producing-anti-urat1-antibody-and-an-immunomodulatory-effect-in-c57bl-6j-mice
#7
Yanjie Ma, Huimin Cao, Zhixin Li, Jinzhi Fang, Xiaomin Wei, Peng Cheng, Rui Jiao, Xiaoran Liu, Ya Li, Yun Xing, Jiali Tang, Liang Jin, Taiming Li
Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60)...
October 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28979780/lesinurad-what-the-nephrologist-should-know
#8
Maria Dolores Sanchez-Niño, Binbin Zheng-Lin, Lara Valiño-Rivas, Ana Belen Sanz, Adrian Mario Ramos, Jose Luño, Marian Goicoechea, Alberto Ortiz
Lesinurad is an oral inhibitor of the monocarboxylic/urate transporter URAT1 encoded by the SLC22A12 gene. Market authorization was granted in February 2016 in Europe and December 2015 in the USA. As a potentially nephrotoxic uricosuric drug acting on the kidney, nephrologists should become familiar with its indications and safety profile. The approved indication is treatment of gout in combination with a xanthine oxidase (XO) inhibitor in adult patients who have not achieved target serum uric acid levels with an XO inhibitor alone...
October 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28870626/immunoreactivity-of-urate-transporters-glut9-and-urat1-is-located-in-epithelial-cells-of-the-choroid-plexus-of-human-brains
#9
Naoya Uemura, Ryuta Murakami, Yoichi Chiba, Ken Yanase, Ryuji Fujihara, Masato Mashima, Koichi Matsumoto, Machi Kawauchi, Gotaro Shirakami, Masaki Ueno
It has been suggested that urate plays a protective role in neurons, while hyperuricemia is correlated with atherosclerosis and cardiovascular disease. However, whether there is a system that directly transports urate into the brain remains to be clarified. In this study, the localization of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), which are known to be representative reabsorptive urate transporters, was immunohistochemically examined in autopsied human brains. Immunoreactivity of GLUT9 was observed on the apical side of the cytoplasm of epithelial cells in the choroid plexus and in the cilia of ependymal cells of the human brain...
October 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28679589/insulin-stimulates-uric-acid-reabsorption-via-regulating-urate-transporter-1-and-atp-binding-cassette-subfamily-g-member-2
#10
COMPARATIVE STUDY
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 urate transporters. In insulin-depleted diabetic rats with streptozotocin treatment, both UA excretion and fractional excretion of UA were increased, suggesting that tubular handling of UA is altered in this model...
September 1, 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
#11
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
#12
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
#13
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
#14
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
#15
REVIEW
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)...
May 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
#16
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
#17
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
#18
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
#19
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
#20
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
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