Uric Acid Levels In Rats Research Articles

Lactobacillus paracasei 259 alleviates hyperuricemia in rats by decreasing uric acid and modulating the gut microbiota

Hyperuricemia (HUA) is a metabolic disease arising from abnormal purine metabolism. It contributes to an increased risk of kidney damage. The present study aimed to investigate the uric acid (UA)-lowering effects of Lactobacillus paracasei 259 isolated from yak yogurt and explore its underlying mechanisms. Our results revealed that L. paracasei 259 decreased the UA levels in rats and inhibited the serum activities of xanthine oxidase. In addition, L. paracasei 259 reduced the levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) in the kidney and altered the expressions of UA transporters (ABC transporter 2 (ABCG2), PDZ domain containing 1 (PDZK1), urate transporter 1 (URAT1), and sodium-phosphate cotransporter type 4 (NPT4)) to near normal levels. Moreover, it increased the abundance of beneficial bacteria in the gut and recovered the gut microbiota composition, promoting the production of short-chain fatty acids (SCFAs). These findings suggested that L. paracasei 259 can potentially be used to decrease UA levels, repair kidney damage, regulate gut microbiota, and alleviate HUA.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 μM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Si Miao San relieves hyperuricemia by regulating intestinal flora.

This study seeks to investigate the therapeutic effects of Si Miao San (SMS) on hyperuricemia and its underlying mechanisms, particularly focusing on the role of intestinal flora. The key components of SMS were identified using high-performance liquid chromatography (HPLC). To establish a rat model of hyperuricemia, an intraperitoneal injection of potassium oxonate was performed, followed by oral administration of various concentrations of SMS. The study evaluated the status of hyperuricemia, renal pathology, xanthine oxidase (XO) activity, and intestinal flora. Utilizing HPLC, we identified five active components of SMS. Following SMS intervention, there was a significant reduction in serum levels of uric acid (UA), blood urea nitrogen, and creatinine, accompanied by an increase in urine UA levels in rats with hyperuricemia. Distinct pathological injuries were evident in the renal tissues of hyperuricemic rats, and these were partially alleviated following SMS intervention. Moreover, SMS exhibited a dose-dependent reduction in XO activity both in the serum and hepatic tissues. Notably, SMS contributed to an enhancement in the diversity of intestinal flora in hyperuricemic rats. The intervention of SMS resulted in a reduction in the abundance of certain bacterial species, including Parabacteroides johnsonii, Corynebacterium urealyticum, and Burkholderiales bacterium. This suggests that SMS may exert anti-hyperuricemia effects, potentially by modulating the composition of intestinal flora.

Uji Efektivitas Ekstrak Etanol Daun Kersen (Muntingia calabura L.) Sebagai Antihiperurisemia Pada Tikus Putih Jantan Yang Di Induksi Kalium Oksonat

Kersen plant (Muntingia calabura L.) is a plant that has many properties and is useful as medicine. Hyperuricemia is a condition where there is an increase in uric acid levels above normal. The leaf part of this plant is widely used by the community as a traditional medicine because of its metabolite compounds. Flavonoid compounds in cherry leaves can reduce uric acid levels through inhibition of the xanthine oxidase enzyme, an enzyme that acts as a catalyst in the oxidation process of hypoxanthine to xanthine and then to uric acid. By inhibiting the work of the xanthine oxidase enzyme, the formation of uric acid will also be inhibited. This study aims to determine the effectiveness of cherry leaf ethanol extract in reducing uric acid levels in male white rats induced by potassium oxonate. This study used an experimental method using 25 male white rats induced by potassium oxonate. The test animals were divided into 5 groups: negative control (CMC Na 1%), positive control (Allopurinol), EEDK dose of 300 mg/kgBB, EEDK dose of 400 mg/kgBB, EEDK dose of 500 mg/kgBB. Measurement of uric acid levels in rats using the point of care testing (POCT) method. All data obtained were analyzed statistically using the One Way Anova test. The results of the analysis showed that there were significant differences between the negative control, positive control, EEDK 300 mg/kg, EEDK 400 mg/kg, and EEDK 500 mg/kg (P<0.05). The most effective dose of cherry leaf ethanol extract as an antihyperuricemia is the EEDK dose of 500 mg/kg BW. There was no significant difference between EEDK 400 mg/kgBW, EEDK 500 mg/kgBW and positive control (P>0.05). Based on the results of the analysis that has been done, it can be concluded that the ethanol extract of cherry leaves has an antihyperuricemia effect in rats. Keywords: Cherry leaves, Hyperuricemia, Potassium oxonate

Effects of Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Fructose and Potassium Oxonate.

Fructose, as a ubiquitous monosaccharide, can promote ATP consumption and elevate circulating Uric Acid (UA) levels. Our previous studies have confirmed that the macroporous resin extract of Dendrobium officinale leaves (DoMRE) could reduce the UA level of rats with hyperuricemia induced by a high-purine diet. This study aimed to investigate whether DoMRE had a UA-lowering effect on rats with hyperuricemia caused by fructose combined with potassium oxonate, so as to further clarify the UA-lowering effect of DoMRE, and to explore the UAlowering effect of DoMRE on both UA production and excretion. Rats with hyperuricemia induced by fructose and potassium oxonate were administered with DoMRE and vehicle control, respectively, to compare the effects of the drugs. At the end of the experiment, the Serum Uric Acid (SUA) and Creatinine (Cr) levels were measured using an automatic biochemical analyzer, the activities of xanthine oxidase (XOD) were measured using an assay kit, and the protein expressions of Urate Transporter 1 (URAT1), glucose transporter 9 (GLUT9), and ATP-Binding Cassette Superfamily G member 2 (ABCG2) were assessed using immune-histochemical and western blot analyses. Hematoxylin and eosin staining was used to assess the histological changes in the kidney, liver, and intestine. Fructose and potassium induced hyperuricemia in rats. Meanwhile, the activities of XOD were markedly augmented, the expression of URAT1 and GLUT9 was promoted, and the expression of ABCG2 was reduced, which were conducive to the elevation of UA. However, exposure to DoMRE reversed these fructose- and potassium oxonate-induced negative alternations in rats. The activities of XOD were recovered to the normal level, reducing UA formation; the expressions of URAT1, ABCG2, and GLUT9 returned to the normal level, resulting in an increase in renal urate excretion. DoMRE reduces UA levels in rats with hyperuricemia induced by fructose combined with potassium oxonate by inhibiting XOD activity and regulating the expression of ABCG2, URAT1, and GLUT9. DoMRE is a potential therapeutic agent for treating hyperuricemia through inhibiting UA formation and promoting UA excretion.

An Analysis of Uric Acid Level Differencebefore and After Chayote Biscuit Treatment (Sechium Module) on Rats (Rattus Norvegicus)

Chayote (Sechium module) is a type of vegetable that can be used for various types of food. It is not native to Indonesia but comes from Thailand. It has a fairly complete nutritional content and is also low in purine content. Besides it can be processed as a vegetable, it can also be processed as biscuits. The results of the laboratory test analysis of the content: uric acid level on rats average before intervention (3.84 mg/dL), and mean uric acid level in the day the 8 of intervention (3.26 mg / dL). Differences in treatment levels: before and after the 8th day (p-value = 0.110). This research was conducted at the Laboratory of the Faculty of Mathematics and Natural Sciences, University of Tadulako. This type of research is a laboratory experimental research using paired t-test statistical tests based on the analysis of uric acid levels in rats (Rattus norvegicus) in 2 interventions (treatments). It is expected that the public will make more use of the chayote (Sechium edule) because there are many nutritional contents in chayote which are very beneficial for the health of the body, especially for gout sufferers.

The Effect of Berberine, a Drug From Chinese Folk Medicine, on Serum and Urinary Uric Acid Levels in Rats With Hyperuricemia.

BackgroundThe principal manifestation of hyperuricemia is gout. Many drugs are in use nowadays to treat gout, but they are linked with multiple side effects. The present study observed berberine (from Chinese folk medicine) on serum and urinary uric acid levels in rats with potassium oxonate-induced hyperuricemia.Materials and methodsThirty-six adult healthy female Sprague Dawley rats were randomly divided into six groups of six rats each. To induce hyperuricemia, all the groups except Group A were given potassium oxonate (250 mg/kg) intraperitoneally on days 1, 3, and 7. Group A, the normal control group, was given normal saline for seven consecutive days intraperitoneally. Group C was administered allopurinol (5 mg/kg body weight) intraperitoneally, and Group D, E, and F were given berberine in doses of 0.75 mg/kg, 1.25 mg/kg, and 2.5 mg/kg body weight respectively intraperitoneally for seven consecutive days, one hour after the potassium oxonate injection. On zero, first, third, and seventh day of the experiment, blood and urine samples were taken to estimate the serum and urinary uric acid levels. On days zero and 7, serum uric acid was measured by cardiac puncture, while on days 1 and 3, it was measured by the tail prick method. The uric acid was measured by an enzymatic colorimetric method and creatinine by the Jaffe method. Fractional excretion of urate was also calculated.ResultsBerberine lowered serum uric acid levels in rats with potassium oxonate-induced hyperuricemia with highly significant results (p-value <0.001) in all three dosages. Berberine increased the urinary uric acid level and the fractional excretion of urate in a time-dependent manner in all three dosages. This effect was maximally shown by low dose berberine with a highly significant result (p-value <0.001).ConclusionBerberine successfully decreased the serum uric acid level of hyperuricemic rats by increasing the urinary uric acid level and fractional excretion of urate.

The Effect of Ethanol Extract of Elephantopus scaber Linn in Decreasing Blood Uric Acid Levels of Hyperuricemic Male Rats

Background: Gout causes attacks of pain and swelling in one or more joints and control of serum uric acid level has been used as one of the therapeutic methods for gout. Inhibition method of xanthine oxidase (XO) activity which can oxidize hypoxanthine to uric acid has been commonly used to decrease serum uric acid level. On the other hand, Elephantopus scaber Linn leaf has been used for the treatment of rheumatoid arthritis as folk medicine by some people in Indonesia.&#x0D; Aims: This study was to determine the hypouricemic effect of ethanol extract of Elephantopus scaber leaf by in vivo study in caffeine (PO)-induced hyperuricemic male rats.&#x0D; Methodology: The E. scaber leaf was obtained from Research Institute for Spices and Medicinal Plants, Bagor, Indonesia. Preparation of E. scaber leaf extract was done by cold maceration extraction technique using ethanol 70%. Male rats (Sprague-Dawley) were induced by using caffeine with dose 27 mg/200 g b.w until the levels in the blood of male rats become hyperuricemic. Equipment (Easy Touch) was used by detecting the level of uric acid in a rat blood. Equipment (Easy Touch) was used by detecting the level of uric acid in a rat blood. Rats were divided into 6 groups, as a positive control was used allopurinol 36 mg/200 g b.w, test preparation were used 3 doses, i.e, 175 mg/200 g b.w, 350 mg/200 g b.w and 700 mg/200 b.w which suspended in Na-CMC 0.5%.&#x0D; Results: The results from a decrease in blood uric acid levels in rats, on the 15th days showed that a dose of 350 mg / 200 g b.w gave decrease in the highest percentage ie 43%. Statistical analysis on the 15th day showed that all of the test preparation groups of E. scaber had effects decrease uric acid in blood serum of rats and significantly different from negative controls (p ≤ 0.05). The dose of 350 mg/200 g b.w of E. scaber had the same effect with a dose of 36 mg/200 g b.w allopurinol in reducing uric acid in experimental rats.&#x0D; Conclusions: E. scaber is a plant that is quite potential to be used in the treatment of gout.

Effects of Toona sinensis Leaf Extract and Its Chemical Constituents on Xanthine Oxidase Activity and Serum Uric Acid Levels in Potassium Oxonate-Induced Hyperuricemic Rats.

Toona sinensis leaf is used as a seasonal vegetable in Korea. A 70% ethanol extract of these leaves exhibited potent xanthine oxidase (XO) inhibition, with a 50% inhibitory concentration (IC50) of 78.4 µM. To investigate the compounds responsible for this effect, bioassay-guided purification led to the isolation of five constituents, identified as quercetin-3-O-rutinoside, quercetin-3-O-β-d-glucopyranoside, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (compound 3), quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside. Compound 3 showed the most potent inhibition of XO, with an IC50 of 2.8 µM. This was similar to that of allopurinol (IC50 = 2.3 µM), which is used clinically to treat hyperuricemia. Kinetic analyses found that compound 3 was a reversible noncompetitive XO inhibitor. In vivo, the T. sinensis leaf extract (300 mg/kg), or compound 3 (40 mg/kg), significantly decreased serum uric acid levels in rats with potassium oxonate-induced hyperuricemia. Furthermore, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified a high level of compound 3 in the leaf extract. These findings suggest that T. sinensis leaves could be developed to produce nutraceutical preparations.

Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells.

Hyperuricaemia (HUA) is an independent risk factor for chronic kidney disease. Urate crystals are deposited in the kidney and can cause renal tubular interstitial fibrosis, leading to renal dysfunction. Chicory extract (hereafter referred to as chicory) clearly reduced serum uric acid levels in rats with HUA induced by 10% fructose. This is the first study to observe the effect of chicory on serum uric acid levels and renal function in rats with HUA and renal injury. In vivo studies using hyperuricaemic rats with renal injury induced by yeast and adenine demonstrated that chicory decreased serum uric acid level, and its effect of delaying the progression of kidney injury was better than that of benzbromarone. In vitro cell experiments showed that this effect is related to the inhibition of GLUT9 protein expression in renal tubules and that lowering blood uric acid concentrations is one of the factors that alleviates renal damage. The results of this study indicate that chicory can be used as an alternative for alleviating renal dysfunction in hyperuricaemia.

Total saponins from dioscorea septemloba thunb reduce serum uric acid levels in rats with hyperuricemia through OATP1A1 up-regulation.

The aim of this study is to evaluate the efficacy of total saponins of Dioscorea (TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups: model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), and organic anion transporting polypeptide 1A1 (OATP1A1) levels were measured. Comparison between the model group and treatment (allopurinol and TSD) groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

Introduction: Chronic allograft dysfunction (CAD) is the primary cause of chronic graft failure after kidney transplantation. The pathogenesis of CAD involves both antigen-dependent and antigen-independent mechanisms. Serum uric acid could have a role in both mechanisms. Review: Hyperuricemia in subjects with renal transplantation is not usually viewed as clinically significant unless the subject develops gout. Drugs used in the treatment of hyperuricemia and gout are more likely to cause side effects in the kidney transplant reciepient. However, there are recent studies that raise the possibility that uric acid could have a role in CAD. Soluble uric acid has been shown to stimulate the proliferation of vascular smooth muscle, to inhibit endothelial cell proliferation and to reduce bioactive levels of endothelial NO. Studies in experimental models have found that hyperuricemia can cause hypertension associated with renal injury characterized by microvascular disease, tubulointerstitial disease, glomerular hypertrophy and glomerulosclerosis. Hyperuricemia was also found to worsen preexistent renal disease, and to be associated with the development of severe vascular lesions that are reminiscent of those observed in CAD. Furthermore, chronic cyclosporine nephropathy is very similar to what is observed in normal rats simply by raising uric acid levels. In addition, raising uric acid levels in rats receiving cyclosporine accelerates the nephropathy whereas lowering uric acid ameliorates the renal lesions. Conclusion: The pathogenic role of uric acid in CAD is still controversial. A controlled clinical trial would be the best approach to determine the effect of uric acid lowering treatment on the development of CAD and long term graft function. Keywords: chronic allograft dysfunction, cyclosporine, uric acid, hyperuricemia, vascular disease

Discovery of 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole, FYX-051-a xanthine oxidoreductase inhibitor for the treatment of hyperuricemia

Our previous study identified 2-[2-(2-methoxy-ethoxy)-ethoxy]-5-[5-(2-methyl-4-pyridyl)-1 H-[1,2,4]triazol-3-yl]-benzonitrile ( 2) as a safe and potent xanthine oxidoreductase (XOR) inhibitor for the treatment of hyperuricemia. Here, we synthesized a series of 3,5-dipyridyl-1,2,4-triazole derivatives and, in particular, examined their in vivo activity in lowering the serum uric acid levels in rats. As a result, we identified 3-(3-cyano-4-pyridyl)-5-(4-pyridyl)-1,2,4-triazole (FYX-051, compound 39) to be one of the most potent XOR inhibitors; it exhibited an extremely potent in vivo activity, weak CYP3A4-inhibitory activity and a better pharmacokinetic profile than compound 2. Compound 39 is currently being evaluated in a phase 2 clinical trial.

The prooxidant effect of sodium metabisulfite in rat liver and kidney

Sodium metabisulfite (Na 2S 2O 5) is used as an antioxidant and antimicrobial agent in a variety of drugs and functions as a preservative in many food preparations. In addition to their antioxidant activity, sulfites oxidize to sulfite radicals ( SO 3 - ) initiating lipid peroxidation. This study was performed to elucidate the effect of subchronic Na 2S 2O 5 (520 mg/kg/day) ingestion on hepatic and renal antioxidant enzyme activities and lipid peroxidation in albino rats. The antioxidant effect of l-carnitine was also tested in rats treated with Na 2S 2O 5. Plasma uric acid levels were monitored in all rats included in the study. Malondialdehyde (MDA) levels significantly increased in Na 2S 2O 5 treated rats vs. controls, with kidney values of 2.21 ± 0.21 vs. 1.22 ± 0.35 and liver values of 79.85 ± 19.5 vs. 31.36 ± 5.0 nmol/mg protein, respectively. Selenium-glutathione peroxidase (GPx) activity was significantly increased in Na 2S 2O 5 treated rats vs. controls, with kidney values of 38.22 ± 2.21 vs. 8.09 ± 0.76 and liver values of 31.11 ± 6.37 vs. 11.70 ± 1.02 U/g protein, respectively. Sodium metabisulfite treatment increased plasma uric acid levels in rats that were included in the study. No protective effect of l-carnitine was observed against lipid peroxidation in both liver and kidneys of rats treated with Na 2S 2O 5. The presented data confirm the prooxidant activity of sulfites and suggest that increased GPx activity and plasma uric acid levels may partially reduce the observed renal and hepatocellular oxidative damage caused via the ingestion of sulfites.

Effects of some drugs on plasma uric acid levels in rats ——-β-agonists.

It has been reported that some drugs containning catecholamines induce hyperuricemia in rats. In this study, the effects of β-agonists and β-antagonists on plasma uric acid levels were examined in potassium-oxonate(250mg/kg i.p.) treated and non-treated rats. Results obtained were as follows: 1)Isoproterenol, salbutamol, terbutaline and trimetoquinol increased plasma uric acid and allantoin in non-treated rats. The order of potency to increase plasma uric acid was iso-proterenol≒salbutamol≒trimetoquinol>terbutaline. 2)In oxonate treated rats, the four β-agonists(50μg/kg i.v.) markedly potentiated a hyperuricemic effect of oxonate. Propranolol(2mg/ kg i.v.) inhibited the effects of β-agonists. In addition, the effect of isoproterenol was inhibited by propranolol(0.25mg/ kg i.v.), but not by atenolol(lmg/kg i.v.). The effect of salbutamol was inhibited by propranolol(0.lmg/kg i.V.), at lower dose than that required for isoproterenol, but not by atenolol(0.5mg/kg i.V.). Plasma allantoin did not change after adminisration of β-agonists and β-antagonists. It is assumed that the hyperuricemic effects of isoproterenol, salbutamol, terbutaline and trimetoquinol are mediated by β-adrenoceptors, and hyperuricemia induced by adrenoceptor stimulation is related to β2-adrenoceptor action.

The Oxonate Pretreated Rat as A Model for Evaluating Hyperuricemic Effects of Antihypertensive Drugs

The oxonate pretreated (uricase inhibited) rat has been evaluated as an in vivo model in which to test the hyperuricemic effects of certain antihypertensive drugs as proposed by Johnson et al. (18). Inhibition of uricase by potassium oxonate pretreatment (2 × 250 mg/kg i.p.) significantly elevated plasma uric acid levels. Allopurinol (50 mg/kg p.o.) blocked the oxonate induced elevation of endogenously synthesized uric acid but had no effect on the response to exogenously administered uric acid. In the oxonate pretreated rat diazoxide (50 mg/kg i.p.) produced a significant elevation in plasma uric acid levels which was blocked by allopurinol. Since diazoxide reduced the urinary uric acid excretion, a renal effect is also implicated. Other agents used in the treatment of hypertension such as hydralazine (6 mg/kg), furosemide (100 mg/kg) and prazosin (10 mg/kg) produced small but significant increases in plasma uric acid levels in rats pretreated with oxonate when administered i.p. The doses of these agents required were greater than those required to produce their characteristic diuretic or antihypertensive effects. The hyperuricemic effects of all three agents were blocked by allopurinol. The present results show that the oxonate pretreated rat can be used to study the effects of drugs on uric acid synthesis in vivo. The data with hydralazine and prazosin, however, showing a hyperuricemia in oxonate pretreated rats when none has been observed during the clinical use of these compounds raises serious question as to its utility as a model for predicting the hyperuricemic liability of new drugs.

Influence of a high fat diet on serum uric acid levels in rats

In present paper the behaviour of uric acid is investigated in serum from rats fed with a 50% fat containing diet in comparison with 3% fat diet as control group. After feeding high-fat diet 5 resp. 52 weeks the level of uric acid is significantly elevated. In the same diet group heavier animals showed higher uric acid levels than lighter animals. In these experiments the age of animals is without influence of the uric acid level in serum.