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https://www.readbyqxmd.com/read/29422889/cordycepin-a-characteristic-bioactive-constituent-in-cordyceps-militaris-ameliorates-hyperuricemia-through-urat1-in-hyperuricemic-mice
#1
Tianqiao Yong, Shaodan Chen, Yizhen Xie, Diling Chen, Jiyan Su, Ou Shuai, Chunwei Jiao, Dan Zuo
Recently, we've reported the anti-hyperuricemic effects of Cordyceps militaris. As a characteristic compound of C. militaris, we hypothesized that cordycepin may play a role in preventing hyperurecimia. Remarkably, cordycepin produced important anti-hyperuricemic actions, decreasing SUA (serum uric acid) to 216, 210, and 203 μmol/L (P < 0.01) at 15, 30, and 60 mg/kg in comparison of hyperuricemic control (337 μmol/L), closing to normal control (202 μmol/L). Elisa, RT-PCR and western blot analysis demonstrated that the actions may be attributed to its downregulation of uric acid transporter 1 (URAT1) in kidney...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29393127/uric-acid-renal-lithiasis-new-concepts
#2
Fabiola Pazos Pérez
BACKGROUND: Uric acid (UA) stones are responsible for 5-10% of the formation of all kidney stones. Recently, an association between UA stones and insulin resistance, diabetes mellitus, and obesity has been demonstrated and so the incidence has increased. The development of UA stones is dependent on several risk factors, including genetic predisposition, geographical location, dietary indiscretion, and various metabolic characteristics. SUMMARY: UA nephrolithiasis can arise from diverse etiologies, all with distinct underlying defects converging to one or more of 3 defects of hyperuricosuria, acidic urine pH, and low urinary volume...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29393121/time-to-target-uric-acid-to-retard-chronic-kidney-disease-progression
#3
Shunya Uchida, Takanori Kumagai, Wen Xiu Chang, Yoshifuru Tamura, Shigeru Shibata
Uric acid (UA) remains a risk factor for the progression of chronic kidney disease (CKD). Most observational studies showed a slight elevation in the serum UA level and this independently predicts the incidence and development of CKD. The recent meta-analysis, however, did not reach the conclusion that urate-lowering therapy with allopurinol retards the progression of CKD. The target level of serum UA if treated is another issue of debate. Our recent analysis by propensity score analysis has shown that the serum UA should be targeted below 6...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29393102/renal-handling-of-uric-acid
#4
Jorge Andrade Sierra, Milagros M Flores Fonseca
Hyperuricemia occurs in 21.4% of the adult population and is associated with several conditions that increase oxidative stress and contributes to the pathogenesis of inflammatory mechanisms for the development and progression of diseases. Serum blood or urine samples of uric acid levels were used to mainly identify clinical problems, depending on the uric acid pathway alterations, which include synthesis, reabsorption or its excretion. Several proteins that act particularly as transporters (URAT1, GLUT9, 1-NPT1, 1-NPT4, OAT4, 9-MCT9, hUAT1, etc...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29382075/systematic-structure-activity-relationship-sar-exploration-of-diarylmethane-backbone-and-discovery-of-a-highly-potent-novel-uric-acid-transporter-1-urat1-inhibitor
#5
Wenqing Cai, Jingwei Wu, Wei Liu, Yafei Xie, Yuqiang Liu, Shuo Zhang, Weiren Xu, Lida Tang, Jianwu Wang, Guilong Zhao
In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a-1x and 1ha-1hi) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC50) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h, which was 200- and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC50 = 0...
January 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29309257/the-slc22-transporter-family-a-paradigm-for-the-impact-of-drug-transporters-on-metabolic-pathways-signaling-and-disease
#6
Sanjay K Nigam
The SLC22 transporter family consists of more than two dozen members, which are expressed in the kidney, the liver, and other tissues. Evolutionary analysis indicates that SLC22 transporters fall into at least six subfamilies: OAT (organic anion transporter), OAT-like, OAT-related, OCT (organic cation transporter), OCTN (organic cation/carnitine transporter), and OCT/OCTN-related. Some-including OAT1 [SLC22A6 or NKT (novel kidney transporter)] and OAT3 (SLC22A8), as well as OCT1 (SLC22A1) and OCT2 (SLC22A2)-are widely studied drug transporters...
January 6, 2018: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/29246027/recent-advances-on-uric-acid-transporters
#7
REVIEW
Liuqing Xu, Yingfeng Shi, Shougang Zhuang, Na Liu
Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia. A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Recent studies also showed that expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29233733/regulation-mechanism-of-dioscin-on-uric-acid-excretion
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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