Uric Acid Excretion Research Articles

Prediction of hyperuricemia in people taking low-dose aspirin using a machine learning algorithm: a cross-sectional study of the National Health and Nutrition Examination Survey.

Background: Hyperuricemia is a serious health problem related to not only gout but also cardiovascular diseases (CVDs). Low-dose aspirin was reported to inhibit uric acid excretion, which leads to hyperuricemia. To decrease hyperuricemia-related CVD, this study aimed to identify the risk of hyperuricemia in people taking aspirin. Method: The original data of this cross-sectional study were obtained from the National Health and Nutrition Examination Survey between 2011 and 2018. Participants who filled in the "Preventive Aspirin Use" questionnaire with a positive answer were included in the analysis. Six machine learning algorithms were screened, and eXtreme Gradient Boosting (XGBoost) was employed to establish a model to predict the risk of hyperuricemia. Results: A total of 805 participants were enrolled in the final analysis, of which 190 participants had hyperuricemia. The participants were divided into a training set and testing set at a ratio of 8:2. The area under the curve for the training set was 0.864 and for the testing set was 0.811. The SHapley Additive exPlanations (SHAP) method was used to evaluate the performances of the modeling. Based on the SHAP results, the feature ranking interpretation showed that the estimated glomerular filtration rate, body mass index, and waist circumference were the three most important features for hyperuricemia in individuals taking aspirin. In addition, triglyceride, hypertension, total cholesterol, high-density lipoprotein, low-density lipoprotein, age, race, and smoking were also correlated with the development of hyperuricemia. Conclusion: A predictive model established by XGBoost algorithms can potentially help clinicians make an early detection of hyperuricemia risk in people taking low-dose aspirin.

Inhibition of the Progression of Chronic Kidney Disease With Hyperuricemia

The final product of the catabolism of purine compounds in humans is uric acid (UA), which is a weak organic acid, over 98% of which is ionized into monosodium urate. UA is excreted by the kidneys, approximately 80-99% is reabsorbed in the proximal tubules of the kidneys. About 20% of UA is excreted through the intestine, where it is destroyed by microflora to carbon dioxide and water. The reference value of UA in blood plasma is 6.5-7 mg/dl in men and 6–6.5 mg/dl in women. The content of UA in the range of 360-400 μmol/l or 6-6.8 mg / dl increases the risk of crystallization under physiological conditions, and regardless of gender. UA levels greater than 7.0 mg/dl are associated with an increased risk of developing gout or nephrolithiasis. Hyperuricemia may occur due to increased production and / or decreased renal excretion of UA. Hyperuricemia is high in the general population and is associated with the development and progression of chronic kidney disease (CKD). Currently, allopurinol and febuxostat are used to correct hyperuricemia. The use of allopurinol should begin with a low dose (50-100 mg/day) and gradually titrate until the target level of UA in the blood is reached or until it is reached to the maximum. If necessary, the dose of allopurinol is increased by 100 mg every 2–4 weeks until the target serum UA level is reached. According to EULAR's recommendations for the treatment of gout, if the target level of UA cannot be achieved with an adequate dose of allopurinol, it should be replaced with febuxostat or uricosuric or a combination of febucostat with uricosuric. Febuxostat is also indicated for allopurinol intolerance. Febuxostat in doses of 80 and 120 mg/day was more effective than allopurinol at a dose of 300 mg/day. With CKD with mild or moderate renal failure, as well as in the elderly, it is not necessary to adjust the dose of febuxostat. The likelihood of reaching the target level of UA in the blood with reduced kidney function is higher in febuxostat. If the patient does not have serious cardiovascular diseases, the patient can be transferred to febuxostat, starting with a dose of 40 mg/day, and gradually titrated, especially in the case of CKD.

Effect and Mechanism of Rhein-praseodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia.

Hyperuricemia (HUA) is a disease characterized by excessive uric acid production and/or insufficient uric acid excretion caused by abnormal purine metabolism in the human body. Uric acid deposition caused by hyperuricemia can cause complications, such as kidney damage. The current therapeutic drugs for HUA are not very targeted and usually have specific toxic side effects. This study aimed to synthesize a compound using rhein and praseodymium, which can effectively help hyperuricemia patients with kidney injury to excrete uric acid through the intestine and preliminarily explore its intestinal excretion mechanism. The natural active ingredient rhein and rare earth metal praseodymium were used to synthesize Rh-Pr. The possible chemical structure of Rh-Pr was deduced by UV, IR, 1H-NMR, conductivity method, and thermogravity analysis. Adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) were administered by gavage for three weeks to establish the hyperuricemia rat model of renal injury. Serum uric acid (UA), creatinine (Cr), urea nitrogen (BUN), and uric acid concentration in urine and feces were detected by biochemical methods. The protein expression levels of GLUT9, ABCG2, and MRP4 in the jejunum, ileum, and colon of rats were detected by Western Blotting. According to the characterization, the chemical composition formula of the complex is Pr(C15H7O6)3·2H2O. In vivo, activity tests showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, upregulate the expression of ABCG2 protein in the jejunum and ileum, down-regulate the expression of GLUT9 protein in the ileum and colon, and also had a good recovery effect on serum uric acid, creatinine, and urea nitrogen levels. Rh-Pr is different from other drugs in that it promotes intestinal uric acid excretion and has a renal recovery effect. It reduces the patient's kidney burden and is significant for hyperuricemia patients with kidney injury.

SLC2A9 rs16890979 reduces uric acid absorption by kidney organoids.

Introduction: The excretion and absorption of uric acid (UA) by the kidneys helps regulate serum UA levels. GLUT9, encoded by SLC2A9, is mainly expressed in the renal tubules responsible for UA absorption. SLC2A9 polymorphisms are associated with different serum UA levels. However, the lack of proper in vitro models has stalled research on the mechanisms of single nucleotide polymorphisms (SNPs) that affect UA metabolism in human urate transporters. Methods: In this study, we constructed a gene-edited human embryonic stem cells-9 (ESC-H9) derived kidney organoid bearing rs16890979, an SLC2A9 missense mutation with undetermined associations with hyperuricemia or hypouricemia. Kidney organoids derived from ESC-H9 with genetical overexpression (OE) and low expression (shRNA) of SLC2A9 to serve as controls to study the function of SLC2A9. The function of rs16890979 on UA metabolism was evaluated after placing the organoids to urate-containing medium and following histopathological analysis. Results: The kidney organoids with heterozygous or homozygous rs16890979 mutations showed normal SLC2A9 expression levels and histological distribution, phenotypically similar to the wild-type controls. However, reduced absorption of UA by the kidney organoids with rs16890979 mutants was observed. This finding together with the observation that UA absorption is increased in organoids with SLC2A9 overexpression and decreased in those with SLC2A9 knockdown, suggest that GLUT9 is responsible for UA absorption, and the rs16890979 SNP may compromise this functionality. Moreover, epithelial-mesenchymal transition (EMT) was detected in organoids after UA treatment, especially in the kidney organoid carrying GLUT9OE, suggesting the cytobiological mechanism explaining the pathological features in hyperuricosuria-related renal injury. Discussion: This study showing the transitional value of kidney organoid modeling the function of SNPs on UA metabolism. With a defined genetic background and a confirmed UA absorption function should be useful for studies on renal histological, cellular, and molecular mechanisms with this organoid model.

Chinese Sumac (Rhus chinensis Mill.) Fruits Prevent Hyperuricemia and Uric Acid Nephropathy in Mice Fed a High-Purine Yeast Diet.

Hyperuricemia (HUA) is a prevalent chronic disease, characterized by excessive blood uric acid levels, that poses a significant health risk. In this study, the preventive effects and potential mechanisms of ethanol extracts from Chinese sumac (Rhus chinensis Mill.) fruits on HUA and uric acid nephropathy were comprehensively investigated. The results demonstrated a significant reduction in uric acid levels in hyperuricemia mice after treatment with Chinese sumac fruit extract, especially in the high-dose group, where the blood uric acid level decreased by 39.56%. Visual diagrams of the kidneys and hematoxylin and eosin (H&E)-stained sections showed the extract's effectiveness in protecting against kidney damage caused by excessive uric acid. Further investigation into its mechanism revealed that the extract prevents and treats hyperuricemia by decreasing uric acid production, enhancing uric acid excretion, and mitigating the oxidative stress and inflammatory reactions induced by excessive uric acid in the kidneys. Specifically, the extract markedly decreased xanthine oxidase (XOD) levels and expression in the liver, elevated the expression of uric acid transporters ABCG2, and lowered the expression of uric acid reabsorption proteins URAT1 and SLC2A9. Simultaneously, it significantly elevated the levels of endogenous antioxidant enzymes (SOD and GSH) while reducing the level of malondialdehyde (MDA). Furthermore, the expression of uric-acid-related proteins NLRP3, ACS, and Caspase-3 and the levels of IL-1β and IL-6 were significantly reduced. The experimental results confirm that Chinese sumac fruit extract can improve HUA and uric acid nephropathy in mice fed a high-purine yeast diet. This finding establishes a theoretical foundation for developing Chinese sumac fruit as a functional food or medicine for preventing and treating HUA.

Commensal Enterococcus faecalis W5 ameliorates hyperuricemia and maintains the epithelial barrier in a hyperuricemia mouse model.

The intestine is responsible for approximately one-third of uric acid (UA) excretion. The effect of commensal Enterococcus faecalis (E. faecalis), one of the most colonized bacteria in the gut, on UA excretion in the intestine remains to be investigated. The aim of this study was to evaluate the effect of commensal E. faecalis on UA metabolism and gut microbiota. The 16SrRNA gene sequencing was used to examine the species of Enterococcus in mouse fecal content. E. faecalis strain was isolated from mouse feces and identified to be E. faecalis W5. The hyperuricemia (HUA) animal model was established with yeast-rich forage and 250 mg·kg-1 ·day-1 potassium oxonate. Oral administration of E. faecalis W5 was given for 20 days, serving as the Efa group. Disrupted intestinal barrier, activated proinflammatory response and low UA excretion in the intestine were found in HUA mice. After E. faecalis W5 treatment, the gut barrier was restored and serum UA level was decreased. Additionally, fecal and intestinal UA levels were elevated, intestinal urate transporter ABCG2 and purine metabolism were upregulated. Moreover, short-chain fatty acid levels were increased, and intestinal inflammation was ameliorated. Commensal E. faecalis W5 ameliorated HUA through reversing the impaired gut barrier, promoting intestinal UA secretion by regulating ABCG2 expression, and decreasing intestinal UA synthesis by regulating purine metabolism. The results may provide the potential for developing treatments for HUA through the intestine.

Research progress of treating hyperuricemia in rats and mice with traditional Chinese medicine.

Hyperuricemia (HUA) is a common chronic metabolic disease caused by abnormal purine metabolism and uric acid excretion. Despite extensive research on HUA, no clear treatment has been found so far. Improving purine metabolism and promoting uric acid excretion is crucial for the effective treatment of HUA. In recent years, traditional Chinese medicine and traditional Chinese medicine prescriptions have shown good effects in treating HUA. This article summarizes the latest progress in treating HUA in rats and mice using traditional Chinese medicine and prescriptions, elaborates on the pathogenesis of HUA, explores the application of commonly used traditional Chinese medicine treatment methods and prescriptions, and discusses the previous pharmacological mechanisms. In general, our research indicates that traditional Chinese medicine can effectively relieve the symptoms related to elevated uric acid levels in HUA rats and mice. However, further exploration and research are needed to verify its efficacy, safety, and feasibility.

Anti-Hyperuricemia Activity and Potential Mechanisms of Medicinal Mushroom Activity: A Review of Preclinical Studies.

Hyperuricemia (HUA) is characterized by abnormally elevated levels of serum uric acid, the product of purine metabolism. The primary symptom of HUA is gout; however, asymptomatic HUA is associated with complications such as hypertension, kidney disease, cardiovascular disease, and metabolic syndrome. The activation of xanthine oxidase (XO), a pivotal enzyme in uric acid biosynthesis, is coupled with extensive reactive oxygen species generation, leading to inflammatory responses, and triggers the development of HUA and its complications. In clinical practice, XO inhibitors are primarily used to treat HUA; however, their prolonged use is accompanied by serious adverse effects. Mushrooms and their bioactive constituents have shown promising anti-HUA activities in both in vitro and in vivo studies, including inhibition of urate production, modulation of renal urate transporters, enhancement of intestinal uric acid excretion, and antioxidant, anti-inflammatory, and antimetabolic syndrome properties. Clinical trials are necessary to validate the beneficial effects and safety of mushrooms in preventing or alleviating HUA and attenuating the associated complications. This review presents contemporary insights into the pathogenesis of HUA, the bioactive components of mushrooms, their therapeutic potential, and the underlying mechanisms involved in ameliorating HUA.

Uric Acid Metabolism, Uric Acid Transporters and Dysuricemia

Serum urate levels are determined by the balance between uric acid production and uric acid excretion capacity from the kidneys and intestinal tract. Dysuricemia, including hyperuricemia and hypouricemia, develops when the balance shifts towards an increase or a decrease in the uric acid pool. Hyperuricemia is mostly a multifactorial genetic disorder involving several disease susceptibility genes and environmental factors. Hypouricemia, on the other hand, is caused by genetic abnormalities. The main genes involved in dysuricemia are xanthine oxidoreductase, an enzyme that produces uric acid, and the urate transporters urate transporter 1/solute carrier family 22 member 12 (URAT1/SLC22A12), glucose transporter 9/solute carrier family 2 member 9 (GLUT9/SLC2A9) and ATP binding cassette subfamily G member 2 (ABCG2). Deficiency of xanthine oxidoreductase results in xanthinuria, a rare disease with marked hypouricemia. Xanthinuria can be due to a single deficiency of xanthine oxidoreductase or in combination with aldehyde oxidase deficiency as well. The latter is caused by a deficiency in molybdenum cofactor sulfurase, which is responsible for adding sulphur atoms to the molybdenum cofactor required for xanthine oxidoreductase and aldehyde oxidase to exert their action. URAT1/SLC22A12 and GLUT9/SLC2A9 are involved in urate reabsorption and their deficiency leads to renal hypouricemia, a condition that is common in Japanese due to URAT1/SLC22A12 deficiency. On the other hand, ABCG2 is involved in the secretion of urate, and many Japanese have single nucleotide polymorphisms that result in its reduced function, leading to hyperuricemia. In particular, severe dysfunction of ABCG2 leads to hyperuricemia with reduced extrarenal excretion.

Effect of ferulic acid and p‐coumaric acid on lowering uric acid through network pharmacology and in vitro studies

AbstractThe occurrence of hyperuricemia is increasing yearly. Based on network pharmacology, this study predicted the molecular targets and signaling pathways of ferulic acid and p‐coumaric acid for improving hyperuricemia. The results were verified through in vitro cell experiments. After enrichment analysis of 11 core targets of ferulic acid and p‐coumaric acid to improve hyperuricemia, the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway was considered as the most significant signaling pathway. In the hyperuricemia cell model, ferulic acid and p‐coumaric acid significantly increased cell viability and decreased the cell uric acid (UA) content. Ferulic acid and p‐coumaric acid significantly regulated the expression of UA transport‐related proteins, namely urate organic anion transporter 1, glucose transporter 9, and adenosine triphosphate‐binding transporter protein G2. Ferulic acid and p‐coumaric acid also downregulated the phosphorylation of PI3K and Akt, which inhibited the PI3K/Akt signaling pathway. This study confirmed that ferulic acid and p‐coumaric acid could regulate UA‐related proteins through the PI3K/Akt pathway and promote UA excretion to alleviate hyperuricemia. The results of this research provided a theoretical basis for further research and development of UA‐lowering products.

Analysis of parameters of purine metabolism in patients with diabetes mellitus type 2

The aim of this research is to comprehensively analyze the current state of purine metabolism as well as assess its features in patients with diabetes mellitus type 2, taking into account the clinical and metabolic polymorphism of the disease. The authors examined 327 patients with diabetes mellitus type 2 (144 men and 183 women), a group of individuals with an average age of 57.8±10.1 years. The average duration of the disease was (9.3±7.3) years. All subjects received oral hypoglycemic therapy. The researchers determined anthropometric indicators, indicators of carbohydrate metabolism, concentration of creatinine, uric acid, parameters of the blood lipid spectrum, purine bases, activity of xanthine oxidase and hypoxanthine-guanine-phosphoribosyltransferase in the blood. In the course of the study the authors verified excretion of uric acid and creatinine renal uric acid, fractional clearance of uric acid, total tubular reabsorption of uric acid and coefficient of complete degradation of purine bases. Using the software complex "Statgraphics Centurion 18.0", we statistically analyzed the obtained data. The research showed that a decrease in assimilation, increased oxidation of purine bases due to the activation of xanthine oxidase, and a decrease in their reutilization by inhibiting the activity of hypoxanthine-guanine-phospho­ribo­syltransferase cause the high intensity of purine catabolism in patients with diabetes mellitus type 2. Hyperuricemia (28.0%), increased creatinine renal uric acid (62.3%), increased coefficient of complete degradation of purine bases (41.6%), activity of xanthine oxidase (38.8%) and inhibition of hypoxanthine-guanine-phosphoribosyltransferase activity (50.3%) dominate in the structure of disorders of purine bases in patients with diabetes mellitus type 2. We found that more than 50% of the subjects had high concentrations of purine bases in the blood. Purine bases concentrations in the blood of patients with diabetes mellitus type 2 closely correlate with each other and with the activity of xanthine oxidase and do not correlate with the level of uricemia, the level of uricemia does not correlate with the level of uric acid excretion. That is, the concentration of uric acid in the blood of patients with diabetes mellitus type 2 does not objectively reflect its production in the body. Patients with diabetes mellitus type 2 with obesity associate hyperuricemia with significantly lower creatinine renal uric acid and fractional clearance of uric acid as well as activation of the anabolic pathway of purine bases deposition.

Recurrent exercise-induced acute kidney injury associated with hypouricemia: a case report and literature review

BackgroundHereditary renal hypouricemia (RHUC) is a heterogenous disorder characterized by defective uric acid (UA) reabsorption resulting in hypouricemia and increased fractional excretion of UA. RHUC is an important cause of exercise-induced acute kidney injury (EIAKI), nephrolithiasis and posterior reversible encephalopathy syndrome (PRES). We present here an unusual case of a patient with RHUC who presented with recurrent EIAKI and had two heterozygous mutations in the SLC2A9 gene.Case presentationA 43-year old man was admitted to our clinic because of bilateral loin pain, nausea and sleeplessness for 3 days after strenuous exercise. The laboratory results revealed increased levels of blood urea nitrogen (BUN) (15 mmol/l) and serum creatinine (Scr) (450 μmol/l), while the UA level was extremely low at 0.54 mg/dl, and his fractional excretion of urate (FE-UA) was 108%. The patient had an episode of acute kidney injury after playing soccer approximately 20 years ago, and on routine physical examination, his UA was less than 0.50 mg/dl. In view of the marked hypouricemia and high FE-UA, a diagnosis of RHUC was suspected, which led us to perform mutational screening of the SLC22A12 and SLC2A9 genes. DNA sequencing revealed no mutation in SLC22A12 gene, but two heterozygous mutations in the SLC2A9 gene.ConclusionsThis is a rare report of a patient with RHUC2 due to the mutation of SLC2A9. And this unique symptom of EIAKI and decreased or normal serum concentrations of UA warrant more attention as an early cue of RHUC.

Data mining-guided alleviation of hyperuricemia by Paeonia veitchii Lynch through inhibition of xanthine oxidase and regulation of renal urate transporters

BackgroundHyperuricemia (HUA) is a metabolic disease characterized by a high level of uric acid (UA). The extensive historical application of traditional Chinese medicine (TCM) offers a range of herbs and prescriptions used for the treatment of HUA-related disorders. However, the core herbs in the prescriptions and their mechanisms have not been sufficiently explained. PurposeOur current investigation aimed to estimate the anti-HUA effect and mechanisms of Paeonia veitchii Lynch, an herb with high use frequency identified from data mining of TCM prescriptions. MethodsPrescriptions for HUA/gout treatment were statistically analyzed through a data mining approach to determine the common nature and use frequency of their composition herbs. The chemical constituents of Paeonia veitchii extract (PVE) were analyzed by UPLC-QTOF-MS/MS, while its UA-lowering effect was further evaluated in adenosine-induced liver cells and potassium oxonate (PO) and hypoxanthine (HX)-induced HUA mice. ResultsA total of 225 prescriptions involving 246 herbs were sorted out. The properties, flavors and meridians of the appearing herbs were mainly cold, bitter and liver, respectively, while their efficacy was primarily concentrated on clearing heat and dispelling wind. Further usage frequency analysis yielded the top 20 most commonly used herbs, in which PVE presented significant inhibitory activity (IC50 = 131.33 µg/ml) against xanthine oxidase (XOD), and its constituents showed strong binding with XOD in a molecular docking study and further were experimentally validated through XOD enzymatic inhibition and surface plasmon resonance (SPR). PVE (50 to 200 μg/ml) dose-dependently decreased UA levels by inhibiting XOD expression and activity in BRL 3A liver cells. In HUA mice, oral administration of PVE exhibited a significant UA-lowering effect, which was attributed to the reduction of UA production by inhibiting XOD activity and expression, as well as the enhancement of UA excretion by regulating renal urate transporters (URAT1, GLUT9, OAT1 and ABCG2). Noticeably, all doses of PVE treatment did not cause any liver injury, and displayed a renal protective effect. ConclusionsOur results first comprehensively clarified the therapeutic effect and mechanisms of PVE against HUA through suppressing UA production and promoting UA excretion with hepatic and renal protection, suggesting that PVE could be a promising UA-lowering candidate with a desirable safety profile for the treatment of HUA and prevention of gout.

Understanding Hyperuricemia: Pathogenesis, Potential Therapeutic Role of Bioactive Peptides, and Assessing Bioactive Peptide Advantages and Challenges.

Hyperuricemia is a medical condition characterized by an elevated level of serum uric acid, closely associated with other metabolic disorders, and its global incidence rate is increasing. Increased synthesis or decreased excretion of uric acid can lead to hyperuricemia. Protein peptides from various food sources have demonstrated potential in treating hyperuricemia, including marine organisms, ovalbumin, milk, nuts, rice, legumes, mushrooms, and protein-rich processing by-products. Through in vitro experiments and the establishment of cell or animal models, it has been proven that these peptides exhibit anti-hyperuricemia biological activities by inhibiting xanthine oxidase activity, downregulating key enzymes in purine metabolism, regulating the expression level of uric acid transporters, and restoring the composition of the intestinal flora. Protein peptides derived from food offer advantages such as a wide range of sources, significant therapeutic benefits, and minimal adverse effects. However, they also face challenges in terms of commercialization. The findings of this review contribute to a better understanding of hyperuricemia and peptides with hyperuricemia-alleviating activity. Furthermore, they provide a theoretical reference for developing new functional foods suitable for individuals with hyperuricemia.

Intestine-Targeted Explosive Hydrogel Microsphere Promotes Uric Acid Excretion for Gout Therapy.

Uric acid metabolism disorder triggers metabolic diseases, especially gout. However, increasing uric acid excretion remains a challenge. Here, an accelerative uric acid excretion pathway via an oral intestine-explosive hydrogel microsphere merely containing uricase and dopamine is reported. After oral administration, uricase is exposed and immobilized on intestinal mucosa along with an in situ dopamine polymerization via a cascade reaction triggered by the intestinal specific environment. By this means, trace amount of uricase is required to in situ up-regulate uric acid transporter proteins of intestinal epithelial cells, causing accelerated intestinal uric acid excretion. From in vitro data, the uric acid in fecal samples from gout patients could be significantly reduced by up to 37% by the mimic mucosa-immobilized uricase on the isolated porcine tissues. Both hyperuricemia and acute gouty arthritis in vivo mouse models confirm the uric acid excretion efficacy of intestine-explosive hydrogel microspheres. Fecal uric acid excretion is increased around 30% and blood uric acid is reduced more than 70%. In addition, 16S ribosomal RNA sequencing showed that the microspheres optimized intestinal flora composition as well. In conclusion, a unique pathway via the intestine in situ regulation to realize an efficient uric acid intestinal excretion for gout therapy is developed.

Synthetic Biohybrids of Red Blood Cells and Cascaded-Enzymes@ Metal-Organic Frameworks for Hyperuricemia Treatment.

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H2 O2 . In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half-life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems.

Pengaruh Aktivitas Fisik Dengan Peningkatan Kadar Asam Urat Dalam Darah Pada Lansia Di RSUD Labuang Baji Sul-Sel

One factor that can influence uric acid levels is physical activity. The activities a person does are related to the level of uric acid in the blood. Physical activity such as exercise or physical movement such as housework will reduce uric acid excretion and increase lactic acid production in the body. The aim of this study was to determine the effect of physical activity on increasing uric acid levels in the blood in elderly patients at Labuang Baji Hospital, Sul-sel. The method used is quantitative with a descriptive research design using a cross sectional approach. To determine the relationship between the independent variable and the dependent variable using joint measurements, the population was 34 people. The sample taken for this study used a total sampling technique so that the results were 34 respondents. The data measurement tool used a questionnaire. The results of research carried out in August 2023 at Labuang Baji Regional Hospital, it can be concluded that there is a relationship between physical activity and uric acid levels in the blood in elderly patients at Labuang Baji Regional Hospital with a p value = (0.036 <0.05). Conclusion From this research, there is a relationship between physical activity and increased uric acid levels in the blood in the elderly at Labuang Baji Regional Hospital, South Sulawesi.

TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter

Gout represents a metabolic ailment resulting from the accumulation of monosodium urate crystals within joints, causing both inflammation and, harm to tissues. The primary contributor to gout’s emergence is an elevated presence of serum urate, which is under the regulation of kidney and, gut urate transporters. Mitigating this risk factor is crucial for averting gout’s onset. Several treatments rooted in TCM and related active compounds have demonstrated efficacy in managing gout, skillfully regulating serum uric acid (UA) levels and curbing inflammation’s progression. This analysis compiles key foundational research concerning the molecular signaling pathways and UA transporters linked to gout, under the regulation of TCM. The focus includes individual botanical drug, active compounds, and TCM formulations, which have been consolidated and examined in this overview. The primary keywords chosen were “gout, hyperuricemia, gouty arthritis, traditional Chinese medicine, Chinese botanical drug, medicinal botanical drug, and natural plant”. Various relevant literature published within the last 5 years were gathered from electronic databases, including PubMed, Web of Science, CNKI, and others. The findings revealed that TCM has the capacity to modulate various signaling pathways, including MAPK, NF-κB, PI3K/Akt, NLRP3 and JAK/STAT. Additionally, it impacts UA transporters like URAT1, GLUT9, ABCG2, as well as OATs and OCTs, thereby contributing to gout treatment. TCM helps maintain a balanced inflammatory interaction and facilitates UA excretion. This study enhances our understanding of TCM’s anti-gout mechanisms and introduces novel perspectives for establishing the clinical significance and future prospects of TCM-based gout treatment.

Amelioration of hyperuricemia by Lactobacillus acidophilus F02 with uric acid-lowering ability via modulation of NLRP3 inflammasome and gut microbiota homeostasis

Hyperuricemia is a metabolic disease caused by disturbances in purine metabolism and imbalances in the formation and excretion of uric acid. It is closely related to the gut microbiota, which is considered a therapeutic target. Some lactic acid bacteria with a uric acid lowering effect have the potential to ameliorate hyperuricemia in the host. However, the mechanism of action remains unclear. Here, we screened a strain of Lactobacillus acidophilus F02 that efficiently degrades uric acid precursors (inosine and guanosine) and further investigated its underlying mechanism on the alleviation of hyperuricemia in high fructose-adenine induced mice. Results showed that L. acidophilus F02 administration reduced serum uric acid levels in hyperuricemia mice by inhibiting xanthine oxidase and adenosine deaminase activity, while protecting hepatorenal injury and systemic inflammation by regulating the relative expression of NLRP3 inflammasome. Most importantly, it restored gut microbial homeostasis and the abundance of bacterial taxa (i.e., a balance in the relative abundance of Firmicutes and Actinobacteria and an increase in the abundance of Bacteroides, Ruminococcus and Lactobacillus). Furthermore, the ability of L. acidophilus F02 to lower uric acid and suppress NLRP3 inflammasome expression was confirmed in the HK-2 cell model, as well as the multiple immunomodulatory effects on RAW264.7 cells. Taken together, we speculate that fructose-adenine induced hyperuricemia triggers hepatorenal injury and gut microbiota dysbiosis, which is ameliorated by L. acidophilus F02. Collectively, the results suggest that lowering uric acid synthesis, increasing uric acid excretion and reducing NLRP3-related IL-1β levels are effective strategies to ameliorate hyperuricemia. Such information could inform future studies on the ecology of L. acidophilus and guide the use of this species for dietary applications in the food industry.

Diuretic Potential of Fenchyl Acetate with Its Mechanism of Action: Toxicity Study.

Hypertension has become a global threat and is one of the greatest risk factors for chronic kidney disease. Fenchyl acetate is a monoterpene that has been assessed for its various pharmacological activities in the past, but no study has evaluated its diuretic potential and the mechanism involved in the diuretic activity after prolonged administration in rats. Therefore, this study aimed to measure the safety and diuretic profile of fenchyl acetate in rats. For evaluating the acute toxicity, a single dose of 2000 mg/kg was administered as per the OECD guideline no. 425, and the rats were observed for 14 days. After 14 days, blood samples were assessed for biochemical, hematological, and oxidative stress parameters. For the acute diuretic study, fenchyl acetate was given in doses of 100, 200, and 400 mg/kg, and urine samples after 8 h were assessed for sodium, potassium, creatinine, uric acid excretion, and urinary output. A single dose of fenchyl acetate (F.A) was selected for prolonged diuretic activity, and furosemide was taken as the standard drug in a repeated dose administration for 7 days. Rats' urine was assessed for pH, sodium, potassium, creatinine, and uric acid excretion along with urinary volume excretion. Furthermore, blood was withdrawn by cardiac puncture, and selected organs like the heart, liver, kidney, and spleen were analyzed for oxidative stress biomarkers. Using pharmacological antagonists or inhibitors, the involvement of L-NAME, acetylcholine, or prostaglandin in F.A.-induced diuresis was determined. Mitochondrial respiratory chain enzyme complexes were also assessed in the kidney homogenates. The acute toxicity results showed F.A to be safe as its LD50 was greater than 2000 mg/kg and there were no signs of mortality or toxicity. The acute diuretic study showed that F.A resulted in a significant and dose-dependent increase in sodium, potassium, creatinine, and uric acid excretion along with urinary output, and these results were comparable to the standard drug furosemide. Prolonged administration with F.A (400 mg/kg) resulted in a comparable excretion of sodium, potassium, creatinine, uric acid, and urine output with furosemide (15 mg/kg). The oxidative stress parameters revealed that F.A (400 mg/kg) resulted in reducing the formation of free radicals. The results from the mechanism-based studies showed the involvement of NO in inducing diuresis. Furthermore, F.A (400 mg/kg) significantly increased the mitochondrial complexes I, II, III, IV, I + III, and II + III in the kidney homogenates, thus restoring the mitochondrial enzymes and improving the renal function. The current study suggests that F.A is safe with a significant diuretic potential with the involvement of NO in its mechanism of action.