• The Korean Journal of Pharmacology
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• v.7 no.1
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• pp.67-76
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• 1971

The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.565-574
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• 2021

Background: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. Methods: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). Results: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1b levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. Conclusion: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

• The Korea Journal of Herbology
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• v.32 no.6
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• pp.23-29
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• 2017

Objective : Hyperuricemia is a metabolic disease characterized by elevated blood uric acid levels, and its prevalence is rapidly increasing worldwide. Alpiniae Oxyphyllae Fructus (AO) belonging to Zingiberaceae is one of well-known traditional medicines in China and Korea, and has been used to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis traditionally. However, the effect of AO has not been studied. In this study we investigated the anti-hyperuricemic effect of AO, and the mechanisms underlying the effect in potassium oxonate (PO)-induced hyperuricemic rats. Methods : To examine the anti-hyperuricemic effects of the AO extract, serum uric acid levels were analyzed in normal and PO-induced hyperuricemic rats. The mechanism underlying the effects of the AO extract on uric acid levels was studied through xanthine oxidase (XOD) activity test and uric acid uptake assay in vitro. The chemical finger printing of the AO extract was analyzed using HPLC-DAD. Results : The AO extract significantly reduced serum uric acid levels in normal as well as PO-induced hyperuricemic rats. It also significantly inhibited the uptake of uric acid in oocytyes and human embryonic kidney cells (HEK293) expressing urate transporter (URAT)1, but not XOD activity in vitro. The chemical finger printing analysis of the AO extract showed nootkatone as a main component. Conclusion : The AO extract exhibits anti-hyperuricemic effects, and these effect were accompanied by increasing excretion of uric acid in kidney. Therefore, the AO extract could be used for prevention or treatment of hyperuicemia and gout.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1534-1540
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• 2005

In order to testify the urate lowering effects of Daihwangmudan-tang(DMT), ICR mice were injected monosodium urate into the abdominal cavity and then DMT was administered on 2 and 4 days after Injection. Uric acid and triglyceride were measured as hematological indices of gout, and some genes related with this change were identified by ACP based GeneFishing PCR method and direct sequencing. From this experiment, DMT highly decreased the blood levels of uric acid and significantly suppressed and lowered the acute increment of triglyceride level. There were 11 differentially expressed genes(DEG) having relations with positive actions of DMT, and 4 major genes in the middle of DEGs were sequenced; Mfap 2, jagged 2, Hsd17b7, DkkI-1, These genes were supposed that several mechanisms through interleukin 1 and T-cell anergy, LDL cholesterol metabolism, wnt pathway would be related with the anti-inflammation effect against gout.

• Childhood Kidney Diseases
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• v.25 no.1
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• pp.44-48
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• 2021

Idiopathic renal hypouricemia (iRHUC) is a rare hereditary disease caused by a defect in urate handling of renal tubules. Type 1 renal hypouricemia (RHUC1) is diagnosed with confirmation of a mutation in SLC22A12 gene which encodes a renal urate-anion exchanger (URAT1). The majority of iRHUC patients are asymptomatic, especially during childhood, and thus many cases go undiagnosed or they are diagnosed late in older age with complications of hematuria, renal stones, or acute kidney injury (AKI). We report a case of a 7-year-old boy with subtle symptoms such as general weakness and dizziness and revealed hypouricemia and incidental nephrolithiasis. Homozygous mutations were detected in the SLC22A12 (c.774G>A) by molecular analysis. The present case suggests that fractional excretion of uric acid (FEUA) screening could be better followed by the coincidental discovery of hypouricemia, to prevent conflicting complications of iRHUC, even with normal urine uric acid to creatinine ratio (U_UA/U_Cr), and sequential genetic analysis if needed.

• Journal of Haehwa Medicine
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• v.17 no.1
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• pp.83-93
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• 2008

In order to study the Effects of yindong(LC) on the variation of blood and joint value the gout induced by microcrystalline sodium urate in rats, for LC is one of the important medicine on gout. After pretreatment of LC(50, 500mg/kg) for 5days, the Effects of LC was evaluated on Serum albumin, Serum globulin, glutamate dxalacetate transminase(AST), glutanate pyruvate transminase(ALT), blood urea nitrogen(BUN), Serum creatitine, Serum uric acid, xanthine oxidase activity, Erythrocyte Sedimentation Rate(ESR), WBC, platelet were measured. The results were obtained as follows : Joint value Increase ratio was not significantly decreased in all LC taken groups compared with the control group. Serum albumin was significantly different in all LC taken groups compared with the control group and Serum globulin was significantly dicreased in 500mg/kgLC taken group compared with the control group. Serum AST, ALT were significantly dicreased in 500mg/kgLC taken group compared with the control group. Serum BUN was significantly decreased in all LC taken groups and Serum creatinine was significantly decreased in 500mg/kgLC taken group compared with the control group. Serum uric acid was significantly different in 500mg/kgLC taken group, and changes in xanthine oxidase activity was significantly decreased in 500mg/kg, 50mg/kgLC taken group. ESR was significantly decreased in all LC taken groups compared with the control group. WBC, platelet count were significantly decreased in 500mg/kgLC taken group compared with the control group. From above results it may be concluded that Yindong can be used for treatment and preventive medcine of gout induced by microcrystalline sodium urate in clinic.

• Journal of Microbiology and Biotechnology
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• v.2 no.4
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• pp.273-277
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• 1992

Treatment of poultry feces with Tolura sp. CH-30 produced a material that was significantly deodorized and showed a promotive effect on plant growth. Tolura sp. CH-30 grew on the poultry feces, deodorizing the feces by assimilation of volatile fatty acids, which are the source of the offensive odor, as a carbon source. Significant degradation of uric acid also occurred. In the treatment of feces with Tolura sp. CH-30, it was possible to deodorize feces in a short time, but reduction in the amount of urate-N was not enough. Urate-N inhibited plant growth due to an excessive nitrogen content produced as a result of rapid decomposition. Therefore, we propose a recycle-treatment plan using poultry feces treated with Tolura sp. CH-30. After the recycle-treatment, the amount of urate-N contained in the recycle-treated poultry feces was small and the recycle-treated poultry feces showed a promotive effect on plant growth when it was added at a nitrogen content of 1.6 g/600 g soil/pot.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.37-48
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• 1991

The characteristics of probenecid effect on renal urate excretion in the cat were studied by clearance method and compared with those in the rabbit. In the cat GFR was $3.03{\pm}0.09\;ml/min{\cdot}kg$, and endogenous plasma urate concentration was $1.12{\pm}0.57\;{\mu}g/ml$, which is less than that in the rabbit $(3.33{\pm}0.46\;{\mu}g/ml)$. In the rabbit, $FE_{ur}$ was $1.76{\pm}0.08$ and net urate secretion was observed, while, in the cat $FE_{ur}$ was $0.70{\pm}0.02$ and net reabsorption was observed. In the cat $FE_{ur}$ was dependent on urine flow and independent of plasma urate concentration. In the rabbit $FE_{ur}$ was suppressed by infusion of probenecid $(30\;mg/kg\;-0.6\;mg/kg{\cdot}min)$ into femoral vein. In the cat the same dose of probenecid increased $FE_{ur}$ and concomitantly increased urine flow. Thus, an increase in $FE_{ur}$ by probenecid could be considered to be resulted from a change in urine flow. In the cat infusion of probenecid $(2.5\;mg/kg{\cdot}min)$ into renal artery markedly suppressed $FE_{P\;A\;H}$, but the effects on $FE_{ur}$ and urine flow were similar to those when probenecid was infused into femoral vein. These results indicate that in the cat kidney urate filtered through glomerulus is reabsorbed by a probenecid-insensitive mechanism with no evidence for net secretion.

• Journal of Haehwa Medicine
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• v.17 no.1
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• pp.95-104
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• 2008

This study was designed to investigate the Effects of Smilacis Glabrae Rhizoma(SGR) on the gout. After pretreatment of SGR(50, 500mg/kg) for 5days, the Effects of SGR was evaluated on changes Joint value increase ratio, Serum albumin, Serum globulin, glutamate dxalacetate transminase(AST), glutanate pyruvate transminase(ALT), blood urea nitrogen(BUN), Serum creatitine, Serum uric acid, xanthine oxidase activity, WBC, Erythrocyte Sedimentation Rate(ESR), platelet. The results were obtained as follows ; Joint valueincrease ratio was decreased in 50mg/kg, 500mg/kg SGR taken group, but changes were not significantly different with the control group. AST, ALT were not significantly different in all SGR taken groups compared with the control group. Serum BUN, creatinine were significantly decreased in 500mg/kg SGR taken group compared with control group. ESR was significantly decreased in all SGR taken groups compared with the control group. WBC, platelet were significantly decreased in 500mg/kg SGR taken group compared with control group. Serum uric acid was not significantly different in all SGR taken groups compared with the control group. Xanthine oxidase activity was significantly decreased in 500mg/kg SGR taken group compared with control group. From above results, it may be concluded that SGR can be used for treatment and prevention of gout.

• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.431-439
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• 2005

Objective: The aim was to identify the inhibitory effects of Flos Bombacis Malabarici(FBM) on Monosodium Urate (MSU)-induced gout in rats. Materials and Methods: After pretreatment of FBM I (50mg/kg), FBM II (125mg/kg) for seven days followed by injection of MSU solution, the various indicators related to gout were measured, such as hematological and serum levels and including joint inflammation. Also, it was investigated whether FBM directly inhibits the activity of xanthine oxidase in vitro. Results: As a result of this study, FBM didn't show the cytotoxicity in Jurkat cells, but it showed significant inhibition of activity of xanthine oxidase in vitro. FBM slightly inhibited joint inflammation induced by MSU though not with statistical significance. FBM partially decreased MSU-induced AST, ALT, BUN, creatinine, WBC, ESR elevation and significantly decreased MSU-induced uric acid in serum. Conclusion: These results suggest that FBM has therapeutic effects that are applicable to prevention and treatment of gout. and should be further investigated.