scholarly journals Morin Improves Urate Excretion and Kidney Function through Regulation of Renal Organic Ion Transporters in Hyperuricemic Mice

2010 ◽  
Vol 13 (3) ◽  
pp. 411 ◽  
Author(s):  
Cai-Ping Wang ◽  
Xing Wang ◽  
Xian Zhang ◽  
Yun-Wei Shi ◽  
Lei Liu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Renal Dysfunction ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Fractional Excretion ◽  
Organic Anion Transporter ◽  
Mrna Levels ◽  
Ion Transporters ◽  
Beneficial Effects ◽  
Anion Transporter

Purpose. Morin (3,5,7,2′,4′-pentahydroxyflavone), a plant-derived flavonoid, has beneficial effects in animals with various diseases including hyperuricemia and renal dysfunction. Since the decreased renal excretion of uric acid is the hallmark of hyperuricemia and renal dysfunction, here we studied the effects of oral morin administration on renal organic ion transporters in oxonate-induced hyperuricemic mice. Methods. The hyperuricemia in mice was induced by potassium oxonate. Uric acid and creatinine concentrations in urine and serum, and fractional excretion of uric acid (FEUA) were performed to evaluate urate handling. Changes in the expression levels of renal organic ion transporters were detected by Western blotting and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results. Morin treatment significantly reduced urinary uric acid/creatinine ratio and FEUA, resulting in the reduction of serum uric acid levels in hyperuricemic mice. And kidney dysfunction was also improved after morin treatment in this model. Protein and mRNA levels of renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1) were significantly decreased, and renal organic anion transporter (mOAT1) levels were remarkably increased in morin-treated hyperuricemic mice. Morin treatment also blocked down-regulation of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in hyperuricemic mice. Conclusion. These results suggest that morin exhibits uricosuric effect via suppressing urate reabsorption and promoting urate secretion in the kidney of hyperuricemic mice and may help to attenuate deleterious effects of hyperuricemia with renal dysfunction.

Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3

Planta Medica ◽  
2015 ◽  
Vol 82 (04) ◽  
pp. 289-297 ◽  
Author(s):  
Wu Hui ◽  
Yuan Yongliang ◽  
Chen Yongde ◽  
Lu Guo ◽  
Lan Li ◽  
...  
Keyword(s):  
Uric Acid ◽  
Renal Dysfunction ◽  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Xanthine Oxidase Activity ◽  
Anion Transporter ◽  
Potassium Oxonate

AbstractEmodinol, 1β,3β,23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our research group, has been demonstrated to exhibit uricosuric activity by our previous study. The aim of this study was to evaluate the uricosuric and nephroprotective effects of emodinol and explore its possible mechanisms in potassium oxonate-induced hyperuricemic mice with renal dysfunction. Mice were orally administrated 250 mg/kg of potassium oxonate once daily for 7 consecutive days to induce hyperuricemia with renal dysfunction. Emodinol was given at doses of 25, 50, and 100 mg/kg on the same day 1 h after oxonate treatment, and allopurinol (10 mg/kg) was given as a positive control. After 1 week, serum uric acid, serum creatinine, urine uric acid, urine creatinine, blood urea nitrogen, and hepatic xanthine oxidase activity were determined. The mRNA and protein levels of urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, oncoprotein-induced transcript 3, and organic cation/carnitine transporters in the kidney were detected by real-time polymerase chain reaction and Western blot analysis. In addition, urinary and renal Tamm-Horsfall glycoprotein concentrations were examined by ELISA assays. Emodinol significantly reduced serum urate levels, increased urinary urate levels and fractional excretion of uric acid, and inhibited hepatic xanthine oxidase activity in hyperuricemic mice. Moreover, potassium oxonate administration led to dys expressions of renal urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, and oncoprotein-induced transcript 3 as well as alternations of uromodulin concentrations, which could be reversed by emodinol. On the other hand, treatment of emodinol caused upregulated expressions of organic cation/carnitine transporters, resulting in an improvement of renal function characterized by decreased serum creatinine and blood urea nitrogen levels. Emodinol exhibited hypouricemic and nephroprotective actions by inhibiting xanthine oxidase activity and regulating renal ion transporters and oncoprotein-induced transcript 3, which may be a potential therapeutic agent in hyperuricemia and renal dysfunction.

scholarly journals Active Components from Lagotis Brachystachya Maintain Uric Acid Homeostasis by Inhibiting Renal TLR4-NLRP3 Signaling in Hyperuricemic Mice

2021 ◽  
Author(s):  
Ji-Xiao Zhu ◽  
Hai-Yan Yang ◽  
Wei-Qiong Hu ◽  
Jie Cheng ◽  
Yang Liu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Underlying Mechanism ◽  
Organic Anion Transporter ◽  
Active Components ◽  
Inflammatory Signaling ◽  
Anion Transporter ◽  
Glucose Transporter 9

Abstract Lagotis brachystachya Maxim is an herb widely used in traditional Tibet medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which were consistent with the finding in the kidney of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind TLR4 and NLRP3. Consistently, western blot showed that the components inhibited TLR4/MyD88/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by the inhibition of inflammatory signaling pathways.

scholarly journals Hypouricemic Effects of Chrysanthemum indicum L. and Cornus officinalis on Hyperuricemia-Induced HepG2 Cells, Renal Cells, and Mice

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1668
Author(s):  
Ok-Kyung Kim ◽  
Jeong-Moon Yun ◽  
Minhee Lee ◽  
Dakyung Kim ◽  
Jeongmin Lee
Keyword(s):  
Uric Acid ◽  
Hepg2 Cells ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Expression Levels ◽  
Cornus Officinalis ◽  
Anion Transporter ◽  
Chrysanthemum Indicum ◽  
Primary Mouse

Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold and Zucc. (Co) on hyperuricemia, both individually and in combination (FSU-CC), using hypoxanthine-treated human liver cancer (HepG2) cells, primary mouse renal proximal tubule cells, and potassium oxonate induced hyperuricemic mice. The Ci contained 7.62 mg/g luteolin and 0 mg/g loganin, Co contained 0 mg/g luteolin and 4.90 mg/g loganin, and FSH-CC contained 3.95 mg/g luteolin and 2.48 mg/g loganin. We found that treatment with Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase while inducing an increase in the expression levels of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) proteins and a decrease in the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group. Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods.

Hypouricemic Effects ofArmillaria melleaon Hyperuricemic Mice Regulated through OAT1 and CNT2

2018 ◽  
Vol 46 (03) ◽  
pp. 585-599 ◽  
Author(s):  
Tianqiao Yong ◽  
Shaodan Chen ◽  
Yizhen Xie ◽  
Diling Chen ◽  
Jiyan Su ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Inhibitory Effect ◽  
Organic Anion Transporter ◽  
Nucleoside Transporter ◽  
Inhibitory Effects ◽  
Concentrative Nucleoside Transporter ◽  
Anion Transporter ◽  
Glucose Transporter 9

Ethanol and water extracts of Armillaria mellea were prepared by directly soaking A. mellea in ethanol (AME) at 65[Formula: see text]C, followed by decocting the remains in water (AMW) at 85[Formula: see text]C. Significantly, AME and AMW at 30, 60 and 120[Formula: see text]mg/kg exhibited excellent hypouricemic actions, causing remarkable declines from hyperuricemic control (351[Formula: see text][Formula: see text]mol/L, [Formula: see text]) to 136, 130 and 115[Formula: see text][Formula: see text]mol/L and 250, 188 and 152[Formula: see text][Formula: see text]mol/L in serum uric acid, correspondingly. In contrast to the evident renal toxicity of allopurinol, these preparations showed little impacts. Moreover, they showed some inhibitory effect on XOD (xanthine oxidase) activity. Compared with hyperuricemic control, protein expressions of OAT1 (organic anion transporter 1) were significantly elevated in AME- and AMW-treated mice. The levels of GLUT9 (glucose transporter 9) expression were significantly decreased by AMW. CNT2 (concentrative nucleoside transporter 2), a key target for purine absorption in gastrointestinal tract was involved in this study, and was verified for its innovative role. Both AME and AMW down-regulated CNT2 proteins in the gastrointestinal tract in hyperuricemic mice. As they exhibited considerable inhibitory effects on XOD, we selected XOD as the target for virtual screening by using molecular docking, and four compounds were hit with high ranks. From the analysis, we concluded that hydrogen bond, Pi–Pi and Pi-sigma interactions might play important roles for their orientations and locations in XOD inhibition.

scholarly journals Prebiotic prevents impaired kidney and renal Oat3 functions in obese rats

2018 ◽  
Vol 237 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Keerati Wanchai ◽  
Sakawdaurn Yasom ◽  
Wannipa Tunapong ◽  
Titikorn Chunchai ◽  
Parameth Thiennimitr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Renal Function ◽  
High Fat Diet ◽  
Organic Anion ◽  
Normal Diet ◽  
Organic Anion Transporter ◽  
High Fat ◽  
Insulin Resistant ◽  
Beneficial Effects ◽  
Anion Transporter

Obesity is health issue worldwide, which can lead to kidney dysfunction. Prebiotics are non-digestible foods that have beneficial effects on health. This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX). XOS was given daily at a dose of 1000 mg for 12 weeks. At week 24, HF rats showed a significant increase in obesity and insulin resistance associated with podocyte injury, increased microalbuminuria, decreased creatinine clearance and impaired Oat3 function. These alterations were improved by XOS supplementation. Renal MDA level and the expression of AT1R, NOX4, p67phox, 4-HNE, phosphorylated PKCα and ERK1/2 were significantly decreased after XOS treatment. In addition, Nrf2-Keap1 pathway, SOD2 and GCLC expression as well as renal apoptosis were also significantly reduced by XOS. These data suggest that XOS could indirectly restore renal function and Oat3 function via the reduction of oxidative stress and apoptosis through the modulating of AT1R-PKCα-NOXs activation in obese insulin-resistant rats. These attenuations were instigated by the improvement of obesity, hyperlipidemia and insulin resistance.

scholarly journals Antioxidant and Renoprotective Effects ofSpirogyra neglecta(Hassall) Kützing Extract in Experimental Type 2 Diabetic Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Atcharaporn Ontawong ◽  
Naruwan Saowakon ◽  
Pornpun Vivithanaporn ◽  
Anchalee Pongchaidecha ◽  
Narissara Lailerd ◽  
...  
Keyword(s):  
Organic Anion ◽  
Diabetic Rats ◽  
Organic Anion Transporter ◽  
Renal Transport ◽  
Type 2 Diabetic Mellitus ◽  
Beneficial Effects ◽  
Anion Transporter ◽  
Renal Morphology ◽  
Type 2 Diabetic

Spirogyra neglectaextract (SNE) has shown antihyperglycemia and antihyperlipidemia in type 2 diabetic mellitus (T2DM) rats. This study investigated the antioxidant and renoprotective effects of SNE in T2DM rats induced by high-fat diet with low-single dose streptozotocin. T2DM rats were fed daily with SNE (0.25, 0.5, and 1 g/kg BW) for 12 weeks. Renal morphology, malondialdehyde levels, qPCR, and western blotting were analyzed. Renal cortical slices were used to determine renal transport of organic anions, which are estrone sulfate andpara-aminohippurate, mediated through organic anion transporter 3-Oat3. Insulin and PKCζwere known to activate Oat3 function while it was inhibited by PKCα. Compared to T2DM, plasma glucose, triglyceride, insulin resistance, renal morphology, and malondialdehyde levels were significantly improved by SNE supplementation. Reduced glutathione peroxidase and nuclear factorκB expressions were related to antioxidant effect of SNE. Oat3 mRNA and protein were not different among groups, but insulin-stimulated rOat3 followed by anion uptakes was abolished in T2DM. This was restored in the slices from SNE treatment. The mechanism of SNE-improved Oat3 was associated with PKCαand PKCζexpressions and activities. These findings indicate that SNE has beneficial effects on renal transport through antioxidant enzymes and PKCs in T2DM rats.

scholarly journals Probenecid, a gout remedy, inhibits pannexin 1 channels

2008 ◽  
Vol 295 (3) ◽  
pp. C761-C767 ◽  
Author(s):  
William Silverman ◽  
Silviu Locovei ◽  
Gerhard Dahl
Keyword(s):  
Uric Acid ◽  
Organic Anion ◽  
Atp Release ◽  
Transport Processes ◽  
Organic Anion Transporter ◽  
Acid Excretion ◽  
Dye Uptake ◽  
Uric Acid Excretion ◽  
Pannexin 1 ◽  
Anion Transporter

Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate. In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus probenecid allows for discrimination between channels formed by connexins and pannexins.

scholarly journals Impact of Lesinurad and Allopurinol on Experimental Hyperuricemia in mice: Biochemical, Molecular and Immunohistochemical Study

2019 ◽  
Author(s):  
Youseef Alghamdi ◽  
Mohamed Mohamed Soliman ◽  
Mohamed Nasan
Keyword(s):  
Uric Acid ◽  
Blood Urea Nitrogen ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Glucose Transporter ◽  
Transforming Growth Factor ◽  
Organic Anion ◽  
Serum Levels ◽  
Urea Nitrogen ◽  
Anion Transporter

Abstract Background : Hyperuricemia is an abnormal increase in uric acid levels in the blood. It is the cause of gout that manifested by inflammatory arthritis and painful disable. Therefore, current study evaluated the potential ameliorative impact of Lesinurad and Allopurinol on the kidneys of hyperuricemic mice at the biochemical, molecular and cellular levels. Methods : Lesinurad and allopurinol alone or in combination were orally administered to hyperuricemic and control mice for seven consecutive days. Levels of uric acid and blood urea nitrogen, along with antioxidants and inflammatory cytokines (IL-1β and TNF-a) were measured in the serum. The mRNA expression of mouse urate anion transporter-1, glucose transporter 9, organic anion transporters, in renal tissues were examined using quantitative real time PCR (qRT-PCR). Simultaneously, the immunoreactivity of transforming growth factor-beta 1 was examined immunohistochemically. Results : Lesinurad and allopurinol administration resulted in significant decrease in serum levels of uric acid, blood urea nitrogen, xanthine oxidase activity, catalase, glutathione peroxidase and inflammatory cytokines (IL-1β and TNF-a) reported in hyperuricemic mice. Both partially reversed oxonate-induced alterations in renal mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expressions, as well as alterations in the immunoreactivity of TGF- β1, resulting in the increase of renal uric acid secretion and excretion. The combined administration of lesinurad and ALP restored all altered parameters in a synergistic manner, improving renal function in the hyperuricemic mouse model employed. Conclusion : This study confirmed synergistic ameliorative hypouricemic impact of both lesinurad and allopurinol in the treatment of hyperuricemia in mice at the biochemical, molecular and cellular levels.

scholarly journals Anti-Hyperuricemic Effect of 2-Hydroxy-4-methoxy-benzophenone-5-sulfonic Acid in Hyperuricemic Mice through XOD

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2671 ◽  
Author(s):  
Tianqiao Yong ◽  
Dan Li ◽  
Muxia Li ◽  
Danling Liang ◽  
Xue Diao ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Glucose Transporter ◽  
Biological Activities ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Negative Effects ◽  
Weight Growth ◽  
General Toxicity ◽  
Anion Transporter ◽  
Glucose Transporter 9

Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking score and xanthine oxidase (XOD) inhibition suggested a good anti-hyperuricemic effect. Then, its anti-hyperuricemic effect, primary mechanisms and general toxicity were examined on a hyperuricemic mouse model which was established using potassium oxonate and hypoxanthine together. HMS demonstrated a remarkable anti- hyperuricemic effect which was near to that of the control drugs, showing promising perspective. General toxicity was assessed and it showed no negative effects on body weight growth and kidney function. Moreover, anti-inflammatory action was observed for HMS via spleen and thymus changes. Its anti-hyperuricemic mechanisms may be ascribed to its inhibition of XOD and its up-regulation of organic anion transporter 1 (OAT1) and down-regulation of glucose transporter 9 (GLUT9).

scholarly journals Chinese Herbal Formulas Si-Wu-Tang and Er-Miao-San Synergistically Ameliorated Hyperuricemia and Renal Impairment in Rats Induced by Adenine and Potassium Oxonate

2015 ◽  
Vol 37 (4) ◽  
pp. 1491-1502 ◽  
Author(s):  
Yongping Guo ◽  
Qian Jiang ◽  
Dingkun Gui ◽  
Niansong Wang
Keyword(s):  
Uric Acid ◽  
Renal Impairment ◽  
Serum Uric Acid ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Protective Effects ◽  
Chinese Herbal ◽  
Renal Histopathology ◽  
Anion Transporter ◽  
Potassium Oxonate

Background/Aims: Hyperuricemia is an independent risk factor for chronic kidney disease and cardiovascular disease. Here, we examined the combined protective effects of Chinese herbal formula Si-Wu-Tang and Er-Miao-San on hyperuricemia and renal impairment in rats. Methods: Rats were randomly divided into normal rats, hyperuricemic rats, and hyperuricemic rats orally administrated with benzbromarone (4.5 mg·kg-1·d-1), Si-Wu-Tang (3.78 g·kg-1·d-1) and Si-Wu-Tang plus Er-Miao-San (6.48 g·kg-1·d-1) for 4 weeks. Hyperuricemic rats were orally gavaged with adenine (0.1 g·kg-1·d-1) and potassium oxonate (1.5 g·kg-1·d-1) daily for 4 weeks. Serum uric acid, creatinine, total cholesterol (TCH), triglyceride and blood urea nitrogen (BUN) concentrations, as well as urinary uric acid and microalbuminuria were measured weekly. Serum xanthine oxidase (XOD) activity and renal histopathology were also evaluated. The renal expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) was detected by western blot. Results: Si-Wu-Tang plus Er-Miao-San lowered serum uric acid, creatinine, triglyceride and BUN levels to a greater degree than did Si-Wu-Tang alone. Si-Wu-Tang plus Er-Miao-San ameliorated microalbuminuria and renal histopathology, as well as decreased serum TCH concentration and XOD activity in hyperuricemic rats. Combination of Si-Wu-Tang and Er-Miao-San also led to a greater increase in OAT1 and OAT3 expression than did Siwutang alone. Conclusion: Si-Wu-Tang and Er-Miao-San synergistically ameliorated hyperuricemia and renal impairment in rats through upregulation of OAT1 and OAT3.

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