scholarly journals The Time-Feature of Uric Acid Excretion in Hyperuricemia Mice Induced by Potassium Oxonate and Adenine

2020 ◽  
Vol 21 (15) ◽  
pp. 5178
Author(s):  
Shaoshi Wen ◽  
Dan Wang ◽  
Haiyang Yu ◽  
Mengyang Liu ◽  
Qian Chen ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Mouse Model ◽  
Uric Acid Level ◽  
Acid Level ◽  
Acid Excretion ◽  
Mice Model ◽  
Uric Acid Excretion ◽  
Plasma Uric Acid ◽  
Potassium Oxonate

Hyperuricemia is an important risk factor of chronic kidney disease, metabolic syndrome and cardiovascular disease. We aimed to assess the time-feature relationship of hyperuricemia mouse model on uric acid excretion and renal function. A hyperuricemia mouse model was established by potassium oxonate (PO) and adenine for 21 days. Ultra Performance Liquid Chromatography was used to determine plasma uric acid level. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and Western blot was used to detect renal urate transporters’ expression. In hyperuricemia mice, plasma uric acid level increased significantly from the 3rd day, and tended to be stable from the 7th day, and the clearance rate of uric acid decreased greatly from the 3rd day. Further study found that the renal organ of hyperuricemia mice showed slight damage from the 3rd day, and significantly deteriorated renal function from the 10th day. In addition, the expression levels of GLUT9 and URAT1 were upregulated from the 3rd day, while ABCG2 and OAT1 were downregulated from the 3rd day, and NPT1 were downregulated from the 7th day in hyperuricemia mice kidney. This paper presents a method suitable for experimental hyperuricemia mouse model, and shows the time-feature of each index in a hyperuricemia mice model.

scholarly journals The effect for hyperuricemia inpatient of uric acid overproduction type or in combination with topiroxostat on the pharmacokinetics, pharmacodynamics and safety of dotinurad, a selective urate reabsorption inhibitor

2019 ◽  
Vol 24 (S1) ◽  
pp. 92-102
Author(s):  
Daisuke Okui ◽  
Tomomitsu Sasaki ◽  
Masahiko Fushimi ◽  
Tetsuo Ohashi
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Combination Group ◽  
Acid Excretion ◽  
Uric Acid Excretion ◽  
Percent Change ◽  
Urate Reabsorption

Abstract Background Dotinurad, a novel selective urate reabsorption inhibitor (SURI), increases urinary uric acid excretion. The aim of this study is to examine the pharmacokinetics, pharmacodynamics, and safety of dotinurad according to the type of hyperuricemia, with or without concomitant use of xanthine oxidase inhibitor, in uric acid “overproduction type” patients. Methods This open-label clinical pharmacology study was conducted in a hospital. Dotinurad 1 mg was administered for 7 days to hyperuricemic patients with uric acid “overproduction type” (overproduction group, n = 6; and combination group, n = 6) and uric acid “underexcretion type” (underexcretion group, n = 6). In the combination group, topiroxostat 80 mg was used concomitantly. Results No significant differences were observed in pharmacokinetics and safety between overproduction group and underexcretion group, and the percent change in serum uric acid level and the amount of urinary uric acid excretion after administration were comparable. In “overproduction type” patients of combination group, the percent change in serum uric acid level significantly increased and the amount of urinary uric acid excretion significantly decreased compared to those of overproduction group. No clinically meaningful differences were observed in safety between the overproduction group and the combination group. Conclusion In inpatients, differences in hyperuricemic type did not significantly influence the pharmacokinetics, pharmacodynamics, and safety of dotinurad. Moreover, in “overproduction type”, the coadministration of dotinurad and topiroxostat had an add-on serum uric acid lowering effect and suppressed urinary uric acid excretion. Trial registration ClinicalTrials.gov Identifier: NCT02837198.

Smilax riparia Reduces Hyperuricemia in Mice as a Potential Treatment of Gout

2014 ◽  
Vol 42 (01) ◽  
pp. 257-259 ◽  
Author(s):  
Xiao-Hui Wu ◽  
Chun-Hao Yu ◽  
Chun-Feng Zhang ◽  
Samantha Anderson ◽  
Yan-Wen Zhang
Keyword(s):  
Uric Acid ◽  
Chinese Medicine ◽  
Herbal Medicine ◽  
Traditional Chinese Medicine ◽  
Mouse Model ◽  
Potential Treatment ◽  
Acid Excretion ◽  
Uric Acid Excretion ◽  
Therapeutic Activities ◽  
Potassium Oxonate

The roots and rhizomes of Smilax riparia, called "Niu-Wei-Cai" in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we examined the efficacy of S. riparia in reducing serum uric acid levels in a potassium oxonate-induced hyperuricemia mouse model. We observed that the total saponins of S. riparia could down-regulate renal mURAT1, resulting in the enhancement of urate excretion in the kidney of hyperuricemic mice. These results suggest that S. riparia could be an active anti-gout herbal medicine, which would contribute to the enhancement of uric acid excretion in the kidney.

Blood Uric Acid Level and IQ: A Study in Twin Families

1984 ◽  
Vol 33 (2) ◽  
pp. 237-242 ◽  
Author(s):  
E. Inouye ◽  
K.S. Park ◽  
A. Asaka
Keyword(s):  
Uric Acid ◽  
Uric Acid Level ◽  
Quantitative Traits ◽  
Acid Level ◽  
Genetic Basis ◽  
Plasma Uric Acid ◽  
Blood Uric Acid ◽  
Twin Children ◽  
Twin Families ◽  
Familial Environment

AbstractApplying newly devised model, heritability (VA/VP) of plasma uric acid level, corrected for age and sex and standardized, was estimated at 0.8 in families consisting of twin parents, spouses and children. Correlation between spouses due to common genotype (ρ) was approximately 0.1, and variance due to common familial environment (VEC/Vp) was -0.3. Analysis of families of selected twin children and their parents resulted in two estimates of heritability: approximately 0.7 and 0.3, ρ being 0.34 and 0.04, and VEC/Vp being 0.04 and 0.34, respectively. Regression of IQ (y) on corrected and standardized plasma uric acid level (x) in the twin children was y = 5.56x + 123, correlation being 0.334 (p < 0.025). The result indicates a genetic basis of blood uric acid level, which may have resulted from polymorphisms in purine metabolism pathway, end product of which is uric acid in man. The significant correlation between plasma uric acid level and IQ suggests a contribution of partly common gene loci to the two quantitative traits.

Clinical Implication of Plasma Uric Acid Level

2009 ◽  
Vol 30 (9) ◽  
pp. 670 ◽  
Author(s):  
Young Tae Shin ◽  
Kyoung Kon Kim ◽  
In Cheol Hwang
Keyword(s):  
Uric Acid ◽  
Uric Acid Level ◽  
Clinical Implication ◽  
Acid Level ◽  
Plasma Uric Acid

scholarly journals A higher baseline plasma uric acid level is an independent predictor of arterial stiffness

Medicine ◽  
2017 ◽  
Vol 96 (6) ◽  
pp. e5957 ◽  
Author(s):  
Xiao-Han Ding ◽  
Xiaona Wang ◽  
Ruihua Cao ◽  
Xu Yang ◽  
Wenkai Xiao ◽  
...  
Keyword(s):  
Uric Acid ◽  
Arterial Stiffness ◽  
Uric Acid Level ◽  
Acid Level ◽  
Independent Predictor ◽  
Plasma Uric Acid

scholarly journals Chicken uric acid elimination via the uric acid transporters BCRP and MRP4 in the liver, kidneys, and intestines

2018 ◽  
Author(s):  
Xuedong Ding ◽  
Manman Li ◽  
Shoufa Qian ◽  
Yuying Ma ◽  
Tianyi Fang ◽  
...  
Keyword(s):  
Renal Function ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Normal Serum ◽  
Control Group ◽  
Cancer Resistance ◽  
Acid Excretion ◽  
Uric Acid Excretion ◽  
Resistance Protein ◽  
Treated Drinking Water

AbstractBreast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that chicken renal proximal tubular epithelial cells participate in uric acid secretion, the roles of BCRP and MRP4 in chickens remain unclear. This study evaluated the relationship between chicken BCRP and MRP4 expression and renal function in the liver, kidneys, and intestines. Sixty 20-day-old Isa brown laying hens were randomly divided into four groups: a control group (NC) and groups provided with sulfonamide-treated drinking water (SD), a diet supplemented with fishmeal (FM), and an intraperitoneal injection of uric acid (IU). Serum uric acid, creatinine, and blood urea nitrogen (BUN) levels were significantly higher in the SD and IU groups than in the NC group. BCRP and MRP4 levels in the SD and IU groups were significantly increased in the kidneys and ileum and decreased in the liver. In the FM group, BCRP and MRP4 were significantly increased in the kidneys and slightly increased in the ileum. These results demonstrate that chicken BCRP and MRP4 are involved in renal and intestinal uric acid excretion. When renal function is impaired, serum uric acid increased and BCRP and MRP4 in the liver, kidneys, and ileum exhibit compensatory increases; when renal function is normal, serum uric acid changes have no effect on ileum BCRP and MRP4 expression. Therefore, this study may provide the references to the uric acid regulation in human.

scholarly journals A REVIEW ON THE EFFECT OF FEBUXOSTAT IN CHRONIC KIDNEY PATIENTS, IT’S SIGNIFICANCE IN eGFR, URIC ACID AND ALBUMINURIA.

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Jinsu Deena Jose ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Uric Acid ◽  
Kidney Disease ◽  
Uric Acid Level ◽  
Acid Level ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Irreversible Reduction ◽  
Risk Of Progression

Chronic kidney disease is defined as the abnormality of the kidney structure or function for≥ 3 months and is associated with an irreversible reduction of the excretory and the endocrine functions of the kidney. An important risk factor for the development and progression of CKD is hyperuricemia. Hyperuricemia can occur as a result of the increased production or the reduced secretion of uric acid. Increased uric acid level is significantly associated with a greater decline in renal function and there is a higher risk of progression into kidney failure. Febuxostat is a nonpurine xanthine oxidase inhibitor for the treatment of hyperuricemia in patients with chronic kidney disease. It reduces serum uric acid concentrations by blocking the transformation of hypoxanthine to xanthine and xanthine to uric acid. Febuxostat is mainly metabolized in the liver and excreted through both urine and feces. Renal adjustment is also not required in CKD patients with mild to moderately reduced eGFR as it is metabolized mainly by glucuronidation and oxidation in the liver and well excreted by both urinary and fecal routes. Recent studies show that, in addition to lowering the uric acid level, febuxostat preserves the eGFR. Keywords:  Chronic kidney disease, hyperuricemia, febuxostat, eGFR

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