Urate oxidase-loaded in PCN-222(Fe) with peroxidase-like activity for colorimetric detection of uric acid

2021 ◽  
Author(s):  
Xiao Liang ◽  
Yingxuan Chen ◽  
Kai Wen ◽  
Haobo Han ◽  
Quanshun Li
Keyword(s):  
Uric Acid ◽  
Colorimetric Detection ◽  
Urate Oxidase ◽  
The Past ◽  
Vital Factor

In the past two decedes, the number of reports on the construction of uric acid (UA) sensors has increased dramatically, as it is a vital factor in the diagnosis of...

scholarly journals Molecular Elucidation of a Urate Oxidase from Deinococcus radiodurans for Hyperuricemia and Gout Therapy

2021 ◽  
Vol 22 (11) ◽  
pp. 5611
Author(s):  
Yi-Chih Chiu ◽  
Ting-Syuan Hsu ◽  
Chen-Yu Huang ◽  
Chun-Hua Hsu
Keyword(s):  
Uric Acid ◽  
High Stability ◽  
Deinococcus Radiodurans ◽  
Catalytic Efficiency ◽  
Enzyme Characterization ◽  
Urate Oxidase ◽  
Medical Applications ◽  
Physiological Conditions ◽  
Extremophile Microorganism ◽  
Mesophilic Conditions

Urate oxidase initiates the uric acid degradation pathways and is extensively used for protein drug development for gout therapy and serum uric acid diagnosis. We first present the biochemical and structural elucidation of a urate oxidase from the extremophile microorganism Deinococcus radiodurans (DrUox). From enzyme characterization, DrUox showed optimal catalytic ability at 30 °C and pH 9.0 with high stability under physiological conditions. Only the Mg2+ ion moderately elevated its activity, which indicates the characteristic of the cofactor-free urate oxidase family. Of note, DrUox is thermostable in mesophilic conditions. It retains almost 100% activity when incubated at 25 °C and 37 °C for 24 h. In this study, we characterized a thermostable urate oxidase, DrUox with high catalytic efficiency and thermal stability, which strengthens its potential for medical applications.

Effect and Mechanism of Total Saponin of Dioscorea on Animal Experimental Hyperuricemia

2006 ◽  
Vol 34 (01) ◽  
pp. 77-85 ◽  
Author(s):  
Guang-Liang Chen ◽  
Wei Wei ◽  
Shu-Yun Xu
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Acid Concentration ◽  
Serum Uric Acid Level ◽  
Urate Oxidase ◽  
Uric Acid Concentration ◽  
Total Saponin ◽  
Test Kit ◽  
Serum Uric Acid Concentration ◽  
Potassium Oxonate

In this study, we investigated the effects and mechanisms of Total Saponin of Dioscorea (TSD) on animal experimental hyperuricemia. Mouse and rat hyperuricemic models were made by orally administering yeast extract paste once a day (30 and 20 g/kg, respectively), for 7 days. Yeast would disturb normal purine metabolism by increasing xanthine oxidase (XOD) activity and generating large quantities of uric acid. This model is similar to human hyperuricemia, which is induced by high-protein diets, due to a purine and nucleic acid metabolic disturbance. Another mouse hyperuricemia model was generated by intraperitoneal injection once with uric acid 250 mg/kg or potassium oxonate 300 mg/kg. Potassium oxonate, a urate oxidase inhibitor, can raise the serum uric acid level by inhibiting the decomposition of uric acid. Likewise, injecting uric acid can also increase serum uric acid concentration. The concentration of uric acid in serum or urine was detected by the phosphotungstic acid method, and the activity of XOD was assayed by a test kit. The results showed that TSD (240, 120 and 60 mg/kg, ig) could significantly lower the level of serum uric acid in hyperuricemic mice. TSD (120 and 60 mg/kg, ig) could also lower the level of serum uric acid in hyperuricemic rats, reduce the activity of XOD in the serum and liver of hyperuricemic rats, and increase the level of urine uric acid concentration as well as 24-hour total uric acid excretion. In conclusion, TSD possesses a potent anti-hyperuricemic effect on hyperuricemic animals, and the mechanism may be relevant in accelerating the excretion and decreasing the production of uric acid.

Follow-Up Study on Management of Tumour Lysis Syndrome with Single Low Fixed Dose (1.5 mg) of Rasburicase - A Tertiary Cancer Centre Experience from India

2021 ◽  
Vol 8 (25) ◽  
pp. 2149-2154
Author(s):  
Alok Ranjan ◽  
Nisha Khanna ◽  
Vivek Ranjan ◽  
Ashwin Kumar
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
Tumour Lysis Syndrome ◽  
Urate Oxidase ◽  
Fixed Dose ◽  
Additional Dose ◽  
Tumour Lysis ◽  
Follow Up Study ◽  
Study Results

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase

High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling

2021 ◽  
Author(s):  
De Xie ◽  
Hairong Zhao ◽  
Jiaming Lu ◽  
Furong He ◽  
Weidong Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uric Acid ◽  
Fatty Acid Synthase ◽  
Specific Inhibitor ◽  
Urate Oxidase ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Lipogenic Gene ◽  
Lipogenic Gene Expression ◽  
Jnk Activation

Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelation between hyperuricemia (HUA) and non-alcoholic fatty liver disease (NAFLD). However, the mechanisms for this association remain unclear. In this study, we investigated the effect of HUA on fat accumulation in human HepG2 hepatoma cells and urate oxidase-knockout (Uox-KO) mice. HUA activated c-Jun N-terminal kinase (JNK) in vivo and in vitro. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased fat accumulation and lipogenic gene expression induced by HUA. Overexpression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase 1 was via activation of JNK, which was blocked by the JNK inhibitor SP600125. HUA activated AP-1 to upregulate lipogenic gene expression via JNK activation. In addition, HUA caused mitochondrial dysfunction and reactive oxygen species production. Pre-treatment with the antioxidant N-acetyl-L-cysteine could ameliorate HUA-activated JNK and hepatic steatosis. These data suggest that ROS/JNK/AP-1 signaling plays an important role in HUA-mediated fat accumulation in liver.

scholarly journals Study on Pegylation of Therapuetic Enzyme Uricase And Its Physio-Chemical Properties For Improving Its Pharmaceutical Characteristics

2013 ◽  
pp. 58-62
Author(s):  
Pooja Nanda ◽  
P.E.Jagdeesh Babu
Keyword(s):  
Uric Acid ◽  
Polyethylene Glycol ◽  
Chemical Properties ◽  
Urate Oxidase ◽  
Purine Catabolism ◽  
Pharmaceutical Properties

Uricase (urate oxidase EC 1.7.3.3, UC) catalyses the oxidation of uric acid, a final product of purine catabolism to allantoin. In the present work, Uricase is bioconjugated using PEG (Polyethylene glycol) as a chemical tool for linking for obtaining conjugates with better and desirable pharmaceutical properties. Uricase from Bacillus fastidisous (Uc) was modified through PEGylation considering various concentrations of linear polyethyleneglycol-8KDa (PEG-8K). The Uc-PEG 8K conjugates, formed by conjugating Uc and PEG-8K in the ratio of 1:15 retained 87.5% of the initial uricolytic activity, and were highly stable at pH 6.0, which is quiet close to physiological pH and at a temperature of 16°C.

scholarly journals Uric Acid Accumulation in an Arabidopsis Urate Oxidase Mutant Impairs Seedling Establishment by Blocking Peroxisome Maintenance

2014 ◽  
Vol 26 (7) ◽  
pp. 3090-3100 ◽  
Author(s):  
Oliver K. Hauck ◽  
Jana Scharnberg ◽  
Nieves Medina Escobar ◽  
Gerhard Wanner ◽  
Patrick Giavalisco ◽  
...  
Keyword(s):  
Uric Acid ◽  
Seedling Establishment ◽  
Urate Oxidase ◽  
Acid Accumulation

scholarly journals Engineering of Bifunctional Enzymes with Uricase and Peroxidase Activities for Simple and Rapid Quantification of Uric Acid in Biological Samples

Catalysts ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 428
Author(s):  
Thanawat Phuadraksa ◽  
Jurairat Chittrakanwong ◽  
Kittitouch Tullayaprayouch ◽  
Naruthai Onsirisakul ◽  
Sineewanlaya Wichit ◽  
...  
Keyword(s):  
Uric Acid ◽  
Low Cost ◽  
Colorimetric Detection ◽  
Amplex Red ◽  
Bifunctional Enzymes ◽  
Bifunctional Proteins ◽  
Frame Fusion ◽  
The Cost ◽  
Optimized Conditions ◽  
Catalyzed Oxidation

Serum uric acid (SUA) is an important biomarker for prognosis and management of gout and other diseases. The development of a low-cost, simple, rapid and reliable assay for SUA detection is of great importance. In the present study, to save the cost of enzyme production and to shorten the reaction time for uric acid quantification, bifunctional proteins with uricase and peroxidase activities were engineered. In-frame fusion of Candida utilis uricase (CUOX) and Vitreoscilla hemoglobin (VHb) resulted in two versions of the bifunctional protein, CUOX-VHb (CV) and VHb-CUOX (VC). To our knowledge, this is the first report to describe the production of proteins with uricase and peroxidase activities. Based on the measurement of the initial rates of the coupled reaction (between uricase and peroxidase), CV was proven to be the most efficient enzyme followed by VC and native enzymes (CUOX+VHb), respectively. CV was further applied for the development of an assay for colorimetric detection of SUA, which was based on VHb-catalyzed oxidation of Amplex Red in the presence of hydrogen peroxide (H2O2). Under the optimized conditions, the assay exhibited a linear relationship between the absorbance and UA concentration over the range of 2.5 to 50 μM, with a detection limit of 1 μM. In addition, the assay can be performed at a single pH (8.0) so adjustment of the pH for peroxidase activity was not required. This advantage helped to further reduce costs and time. The developed assay was also successfully applied to detect UA in pooled human serum with the recoveries over 94.8%. These results suggest that the proposed assay holds great potential for clinical application.

scholarly journals Association of Hyperuricemia With Immune Disorders and Intestinal Barrier Dysfunction

2020 ◽  
Vol 11 ◽  
Author(s):  
Qiulan Lv ◽  
Daxing Xu ◽  
Xuezhi Zhang ◽  
Xiaomin Yang ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Urate Oxidase ◽  
Intestinal Immunity ◽  
Immune Disorders ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Gut Barrier Function ◽  
Tnf Α

BackgroundMore than 30–40% of uric acid is excreted via the intestine, and the dysfunction of intestinal epithelium disrupts uric acid excretion. The involvement of gut microbiota in hyperuricemia has been reported in previous studies, but the changes and mechanisms of intestinal immunity in hyperuricemia are still unknown.MethodsThis study developed a urate oxidase (Uox)-knockout (Uox–/–) mouse model for hyperuricemia using CRISPR/Cas9 technology. The lipometabolism was assessed by measuring changes in biochemical indicators. Furthermore, 4-kDa fluorescein isothiocyanate–labeled dextran was used to assess gut barrier function. Also, 16S rRNA sequencing was performed to examine the changes in gut microbiota in mouse feces. RNA sequencing, Western blot, Q-PCR, ELISA, and immunohistochemical analysis were used for measuring gene transcription, the number of immune cells, and the levels of cytokines in intestinal tissues, serum, kidney, liver, pancreas, and vascellum.ResultsThis study showed that the abundance of inflammation-related microbiota increased in hyperuricemic mice. The microbial pattern recognition–associated Toll-like receptor pathway and inflammation-associated TNF and NF-kappa B signaling pathways were significantly enriched. The increased abundance of inflammation-related microbiota resulted in immune disorders and intestinal barrier dysfunction by upregulating TLR2/4/5 and promoting the release of IL-1β and TNF-α. The levels of epithelial tight junction proteins occludin and claudin-1 decreased. The expression of the pro-apoptotic gene Bax increased. The levels of LPS and TNF-α in systemic circulation increased in hyperuricemic mice. A positive correlation was observed between the increase in intestinal permeability and serum levels of uric acid.ConclusionHyperuricemia was characterized by dysregulated intestinal immunity, compromised intestinal barrier, and systemic inflammation. These findings might serve as a basis for future novel therapeutic interventions for hyperuricemia.

Point-of-care testing (POCT) of patients with a high concentration of uric acid by using alginate hydrogel microspheres embedded with CdZnTeS QDs and urate oxidase (Alg@QDs-UOx MSs)

The Analyst ◽  
2021 ◽  
Author(s):  
Fan Lu ◽  
Yeling Yang ◽  
Yucheng Liu ◽  
Fubing Wang ◽  
Xinghu Ji ◽  
...  
Keyword(s):  
Uric Acid ◽  
Convenient Method ◽  
Point Of Care ◽  
Urate Oxidase ◽  
Point Of Care Testing ◽  
High Concentration ◽  
Alginate Hydrogel ◽  
Hydrogel Microspheres

A more convenient method for POCT of patients with a high concentration of uric acid by using Alg@QDs-UOx MSs is developed.

Recommandations of the Societe Francaise des Cancers de l’Enfant (SFCE) for the Management of Tumors Lysis Syndrom (TLS) : A Validation Survey.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5295-5295
Author(s):  
Y. Bertrand ◽  
A. Auvrignon ◽  
B. Nelken ◽  
V. Mialou ◽  
F. Mechinaud ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Creatinine ◽  
Acid Concentration ◽  
Lymphoblastic Leukemia ◽  
Urate Oxidase ◽  
Uric Acid Concentration ◽  
Plasma Uric Acid ◽  
Non Hodgkin Lymphoma ◽  
Metabolic Complication ◽  
Oxidase Enzyme

Abstract TLS is a frequent metabolic complication of hematologic malignant diseases which can generate important renal impairment. As described in previous studies (Goldman S.C. et al, Blood2001;97, 2998–3003 and Pui C.H. et al., J.Clin.Oncol.2001;19, 697–704), there are High Risk (HR) patients (pts) of TLS. Rasburicase a recombinant urate oxidase enzyme transforms uric acid into the highly soluble compound allantoin which is then excreted by the kidneys. Rasburicase is highly effective in prevention and treatment of TLS. Based on these studies, the SFCE made the following recommandations for the management of TLS in children. HR pts are defined as : B cell Acute Lymphoblastic Leukemia (ALL), ALL or Acute Myeloblastic Leukemia (AML) with initial leukocyte count of at least 50x109/L, Stage III and IV T or B Non Hodgkin Lymphoma (NHL), any leukemia or NHL with a plasma uric acid concentration of at least 300 mmoles/L if <10 years old or 350 mmoles/L if >10 years old, serum creatinine or lactate deshydrogenase concentration (LDH) exciding twice the upper limit of normal (N), hyperphosphatemia ≥2mmoles/L. These pts are treated by hyperhydratation (3L/m2) ±alkaline and Rasburicase 0,20 mg/kg/d x 5days. Rasburicase is carried on if serum creatinine > 1,5N or phosphatemia >3mmoles/L or plasma uric acid concentration ≥200mmoles/L and until normalization. Low Risk (LR) pts are defined as pts not HR. They are treated by hyperhydratation (3L/m2) and Rasburicase 0,20 mg/kg/d for one day only. Rasburicase is carried on during 4 days or more on the same biological basis as HR pts. In order to check the validity of those guidelines, we are conducting a survey looking at the evolution of the pts managed according to the SFCE recommandations.150 pts are planned for a 6 months study. On July 30th, 39 pts are registred : 25 ALL, 6 AML, 8 NHL (3 Burkitt). At that time there is no SLT complication. Results will be presented at the 2004 ASH Meeting.

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