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Alterations of serum and saliva oxidative markers in patients with bronchial asthma

Abboud MM, Al-Rawashde FA, Al-Zayadneh EM

J Asthma, 2022 Nov;59(11):2154-2161.
PMID: 34855555 DOI: 10.1080/02770903.2021.2008426

BACKGROUNDS: The development of asthma is highly affected by exposure to exogenous and endogenous oxidative molecules, but the impact of this exposure on the pathophysiology of asthma has received little attention.
OBJECTIVES: Evaluating group of selective oxidative stress markers as a tool in the management of asthma disease.
METHODS: In comparison with matched healthy controls, levels of the oxidant and antioxidant markers: lipid peroxidation malondialdehyde (MDA), Total glutathione (tGSH), Uric acid (UA), Glutathione peroxidase (GPx), Catalase (CAT) superoxide dismutase (SOD), and Total antioxidant capacity (TAC) were assessed in serum and saliva of different asthma groups.
RESULTS: All oxidative markers in serum and saliva of asthma patients showed significant alterations from normal healthy controls (P 0.05).
CONCLUSION: Determination of the oxidative markers GPx, CAT, UA in serum or saliva can distinguish asthma from healthy states. The serum levels of UA and TAC are highly effective in monitoring asthma severity, while the salivary GPx, CAT, UA, MDA are beneficial in the management of childhood asthma. Discrimination of the age factor between asthma groups can be achieved by testing GPx, SOD, TAC in serum.

Matched MeSH terms: Uric Acid
Optimized fabrication of newly cholesterol biosensor based on nanocellulose

Abdi MM, Razalli RL, Tahir PM, Chaibakhsh N, Hassani M, Mir M

Int J Biol Macromol, 2019 Apr 01;126:1213-1222.
PMID: 30611809 DOI: 10.1016/j.ijbiomac.2019.01.001

A novel and sensitive electrochemical cholesterol biosensor was developed based on immobilization cholesterol oxidase (ChOx) on the polyaniline/crystalline nanocellulose/ionic liquid modified Screen-Printed Electrode (PANi/CNC/IL/SPE). A thin layer of ionic liquid (IL) was spin coated on the modified electrode to enhance the electron transferring. Crystalline nanocellulose was prepared from Semantan bamboo (Gigantochloa scortechinii) via acid hydrolysis and it was used to synthesize a nanocomposite of PANi/CNC via in situ oxidative polymerization process. FESEM and TEM images showed high porosity of the nanostructure with no phase separation, revealing the homogenous polymerization of the monomer on the surface of the crystalline cellulose. Research surface methodology (RSM) was carried out to optimize the parameters and conditions leading to maximize the performance and sensitivity of biosensors. The PANi/CNC/IL/GLU/ChOx-modified electrode showed a high sensitivity value of 35.19 μA mM/cm-2 at optimized conditions. The proposed biosensor exhibited a dynamic linear range of 1 μM to 12 mM (R2 = 0.99083) with the low Limit of Detection of 0.48 μM for cholesterol determination. An acceptable reproducibility (RSDs ≤3.76%) and repeatability (RSDs ≤3.31%) with the minimal interference from the coexisting electroactive compounds such as ascorbic acid, uric acid and glucose was observed for proposed biosensor.

Matched MeSH terms: Uric Acid
Enhancing uric acid electrochemical detection with copper ion-activated mini protein mimicking uricase within ZIF-8: response surface methodology (RSM) optimization

Abdul Aziz SFN, Hui OS, Salleh AB, Normi YM, Yusof NA, Ashari SE, et al.

Anal Bioanal Chem, 2024 Jan;416(1):227-241.
PMID: 37938411 DOI: 10.1007/s00216-023-05011-z

This study aims to investigate the influence of copper(II) ions as a cofactor on the electrochemical performance of a biocomposite consisting of a mini protein mimicking uricase (mp20) and zeolitic immidazolate framework-8 (ZIF-8) for the detection of uric acid. A central composite design (CCD) was utilized to optimize the independent investigation, including pH, deposition potential, and deposition time, while the current response resulting from the electrocatalytic oxidation of uric acid was used as the response. The statistical analysis of variance (ANOVA) showed a good correlation between the experimental and predicted data, with a residual standard error percentage (RSE%) of less than 2% for predicting optimal conditions. The synergistic effect of the nanoporous ZIF-8 host, Cu(II)-activated mp20, and reduced graphene oxide (rGO) layer resulted in a highly sensitive biosensor with a limit of detection (LOD) of 0.21 μM and a reproducibility of the response (RSD = 0.63%). The Cu(II)-activated mp20@ZIF-8/rGO/SPCE was highly selective in the presence of common interferents, and the fabricated layer exhibited remarkable stability with signal changes below 4.15% after 60 days. The biosensor's reliable performance was confirmed through real sample analyses of human serum and urine, with comparable recovery values to conventional HPLC.

Matched MeSH terms: Uric Acid/analysis
Fulltext The use of febuxostat for gout in Hospital Tengku Ampuan Afzan (HTAA) Kuantan. [Abstract]

Abdullah H

International Medical Journal Malaysia, 2017;16(11):50.
MyJurnal

Introduction: Febuxostat is a non-purine-selective oral xanthine oxidase inhibitor drug, and is an alternative to Allopurinol to lower serum uric acid in gout patients. It is probably more effective than Allopurinol, however, its use is limited because of its cost and availability. Allopurinol has been the mainstay treatment for gout for about 50 years. However, its use has been associated with allergic reactions especially in patients with renal impairment.The objective of this study was to describe HTAA Rheumatology Unit experiences with Febuxostat in the management of gout.
Materials and method: Case records belonging to 6 patients who had been started on Febuxostat between January 2012 and January 2017 were analysed.
Results: The majority of patients on Febuxostat were males (83.3%) as well as Malays (83.3%). About 66.7% of patients had already developed mild to moderate chronic kidney disease (GFR between 30-89 mL/min) due to multifactorial causes by the time they were started on Febuxostat. Also 33% of patients had mild liver impairment (ALT & AST < 1.5 ULN) due to fatty liver prior to Febuxostat. All patients had been started on Febuxostat due to allergic reactions to Allopurinol. All patients were on Febuxostat 40 mg once a day. Following Febuxostat, a significant decrease in the uric acid levels much closer to the target level i.e. less than 360 µmol/L were achieved in all patients. Only 1 patient (16.7%) developed a side effect i.e. ALT > 1.5 ULN while the rest tolerated the drug very well.
Conclusion: Although the number of patients analysed was small, Febuxostat was shown to be very effective and safe for use in patients with gout even with concomitant mild to moderate renal impairment. Serum uric acid levels reduced significantly while on the lowest dose of 40 mg once a day.

Matched MeSH terms: Uric Acid
Fulltext In vivo detection of monosodium urate crystal deposits by Raman spectroscopy-a pilot study

Abhishek A, Curran DJ, Bilwani F, Jones AC, Towler MR, Doherty M

Rheumatology (Oxford), 2016 Feb;55(2):379-80.
PMID: 26342227 DOI: 10.1093/rheumatology/kev339

Study done in England

Matched MeSH terms: Uric Acid/analysis*
Fulltext Optimization of Extraction Conditions of Phytochemical Compounds and Anti-Gout Activity of Euphorbia hirta L. (Ara Tanah) Using Response Surface Methodology and Liquid Chromatography-Mass Spectrometry (LC-MS) Analysis

Abu Bakar FI, Abu Bakar MF, Abdullah N, Endrini S, Fatmawati S

Evid Based Complement Alternat Med, 2020;2020:4501261.
PMID: 32047524 DOI: 10.1155/2020/4501261

Gout is a common disease affected most of the people due to the elevation of uric acid in the blood. Flavonoid and phenolic compounds are reported to exert the anti-gout activity of medicinal plants. Hence, this study aimed at optimizing the extraction conditions of phenolic and flavonoid compounds as well as the anti-gout (xanthine oxidase inhibitory activity) in vitro of Euphorbia hirta using response surface methodology (RSM). The plant part used was the whole plant excluding roots. The effects of three independent variables (extraction time, X1; extraction temperature, X2; and solid-to-liquid ratio, X3) on three response variables (total flavonoid content, Y1; total phenolic content, Y2; and xanthine oxidase inhibitory activity, Y3) were determined using central composite design (CCD) while phytochemical profiling of the extracts was determined by liquid chromatography-mass spectrometry (LC-MS). Quadratic models produced a satisfactory fitting of the experimental data with regard to total flavonoid content (r2 = 0.9407, p < 0.0001), total phenolic content (r2 = 0.9383, p < 0.0001), and xanthine oxidase inhibitory activity (r2 = 0.9794, p < 0.0001). The best extraction conditions observed for total flavonoid content, total phenolic content, and xanthine oxidase inhibitory activity were at a temperature of 79.07°C for 17.42 min with solid-to-liquid ratio of 1 : 20 g/ml. The optimum values for total flavonoid, total phenolic, and xanthine oxidase inhibitory activity were 67.56 mg RE/g, 155.21 mg GAE/g, and 91.42%, respectively. The main phytochemical compounds in the optimized E. hirta extract are neochlorogenic acid, quercetin-3β-D-glucoside, syringic acid, caffeic acid, ellagic acid, astragalin, afzelin, and quercetin. As conclusion, this study clearly demonstrated the best conditions to obtain higher xanthine oxidase inhibitory activity and phytochemical compounds which can be further used for the development of anti-gout agents.

Matched MeSH terms: Uric Acid
Fulltext Effects of Quercetin on Tubular Cell Apoptosis and Kidney Damage in Rats Induced by Titanium Dioxide Nanoparticles

Alidadi H, Khorsandi L, Shirani M

Malays J Med Sci, 2018 Mar;25(2):72-81.
PMID: 30918457 DOI: 10.21315/mjms2018.25.2.8

Background: Recent studies have demonstrated that many nanoparticles have an adverse or toxic effect on the kidney.
Objective: To investigate the nephroprotective effect of quercetin (QT) against renal injury induced by titanium dioxide nanoparticles (NTiO2) in rats.
Methods: NTiO2-intoxicated rats received 50 mg/kg of NTiO2 for seven days. The QT + NTiO2 group was pretreated with QT for seven days before being administered NTiO2. Uric acid, creatinine, and blood urea nitrogen were considered to be biomarkers of nephrotoxicity. Catalase (CAT) and superoxide dismutase (SOD) activities and renal levels of malondialdehyde (MDA) were measured to assess the oxidative stress caused by NTiO2.
Results: NTiO2 significantly increased the plasma level of the biomarkers. It also significantly decreased the activities of CAT (P = 0.008) and SOD (P = 0.004), and significantly increased the MDA levels (P = 0.007). NTiO2 caused proximal tubule damage, the accumulation of red blood cells, the infiltration of inflammatory cells, and reduced the glomerular diameters, as well as induced apoptosis in the proximal tubules. Pre-treatment with QT attenuated the histological changes, normalised the plasma biomarkers, suppressed oxidative stress, ameliorated the activities of CAT (P = 0.007) and SOD (P = 0.006), and reduced apoptosis (P < 0.001).
Conclusion: QT was found to have a potent protective effect against nephrotoxicity induced by NTiO2 in rats. It also reduced apoptosis caused by NTiO2.

Matched MeSH terms: Uric Acid
Fulltext Global metabolomics profiling of colorectal cancer in Malaysian patients

Amir Hashim NA, Ab-Rahim S, Wan Ngah WZ, Nathan S, Ab Mutalib NS, Sagap I, et al.

Bioimpacts, 2021;11(1):33-43.
PMID: 33469506 DOI: 10.34172/bi.2021.05

Introduction:
The serum metabolomics approach has been used to identify metabolite biomarkers that can diagnose colorectal cancer (CRC) accurately and specifically. However, the biomarkers identified differ between studies suggesting that more studies need to be performed to understand the influence of genetic and environmental factors. Therefore, this study aimed to identify biomarkers and affected metabolic pathways in Malaysian CRC patients.
Methods:
Serum from 50 healthy controls and 50 CRC patients were collected at UKM Medical Centre. The samples were deproteinized with acetonitrile and untargeted metabolomics profile determined using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOFMS, Agilent USA). The data were analysed using Mass Profiler Professional (Agilent, USA) software. The panel of biomarkers determined were then used to identify CRC from a new set of 20 matched samples.
Results:
Eleven differential metabolites were identified whose levels were significantly different between CRC patients compared to normal controls. Based on the analysis of the area under the curve, 7 of these metabolites showed high sensitivity and specificity as biomarkers. The use of the 11 metabolites on a new set of samples was able to differentiate CRC from normal samples with 80% accuracy. These metabolites were hypoxanthine, acetylcarnitine, xanthine, uric acid, tyrosine, methionine, lysoPC, lysoPE, citric acid, 5-oxoproline, and pipercolic acid. The data also showed that the most perturbed pathways in CRC were purine, catecholamine, and amino acid metabolisms.
Conclusion:
Serum metabolomics profiling can be used to identify distinguishing biomarkers for CRC as well as to further our knowledge of its pathophysiological mechanisms.

Matched MeSH terms: Uric Acid
Fulltext Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Anwar F, Saleem U, Rehman AU, Ahmad B, Froeyen M, Mirza MU, et al.

Front Pharmacol, 2021;12:607026.
PMID: 34040515 DOI: 10.3389/fphar.2021.607026

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD
50
. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.

Matched MeSH terms: Uric Acid
Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats

Arafat OM, Tham SY, Sadikun A, Zhari I, Haughton PJ, Asmawi MZ

J Ethnopharmacol, 2008 Aug 13;118(3):354-60.
PMID: 18602231 DOI: 10.1016/j.jep.2008.04.015

AIM OF THE STUDY: Orthosiphon stamineus (Labiatae) is a traditional folk medicine widely used in Southeast Asia for the treatment of several kidney disorders, gout and as a diuretic. This study was conducted to examine the diuretic and hypouricemic effects of Orthosiphon stamineus leaf extracts.
MATERIALS AND METHODS: The diuretic effect of different methanol extracts was examined by treating different groups of Sprague-Dawley rats with single (2g/kg) oral doses of methanol and methanol:water (1:1) extracts. Hydrochlorothiazide (10mg/kg) was used as positive control in acute study. Methanol and methanol water (1:1) extracts at 0.5 g/kg were administered for a period of 7 consecutive days. Cumulative urine volume and electrolytes (Na+ and K+) concentrations at different time intervals were measured. On the other hand, hypouricemic activity of methanol:water extract (1:1) was experimented using different oral single doses (0.25, 0.5, 1 and 2g/kg). Allopurinol was used as positive control. Uric acid concentration in serum was analyzed by using RP-HPLC at 280 nm.
RESULTS: Sodium and potassium excretion increased significantly (p<0.05 and <0.01) in the first 8h of treatment with a single dose (2g/kg) of the extracts in a pattern comparable to that of the known diuretic hydrochlorothiazide. Meanwhile, repeated administration of 0.5 g/kg methanol:water (1:1) extract showed a significant increase in urine volume (from day 3 to day 7) (p<0.01) and electrolytes excretion (Na+ and K+) from day 2 to day 7 (p<0.05 and <0.01). On the other hand, 0.5, 1 and 2g/kg of methanol:water (1:1) extract and the standard allopurinol reduced the serum urate level in hyperuricemic rats at hour 6.
CONCLUSION: These results provided an evidence of the high tendency of methanol:water (1:1) extract of Orthosiphon stamineus towards diuretic and hypouricemic effects in rats.

Matched MeSH terms: Uric Acid/blood*
A survey of the primary care management of osteoarthritis in Malaysia: A view from a rheumatologist's perspective

Arshad A, Rashid R, Das Gupta E

Int J Rheum Dis, 2008;11(3):246-250.
DOI: 10.1111/j.1756-185X.2008.00367.x

Objective: Primary care management of knee osteoarthritis (OA) has received little attention in the scientific literature and the main reason for this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting.
Methods: A cross-sectional survey of 200 randomly selected general practitioners (GPs) in the peninsular states of Malaysia was undertaken using a questionnaire. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment. They were also asked about their usage of conventional and complementary medication.
Results: One hundred and eighty (90%) GPs responded to the questionnaires sent: 77% were in solo practice and 33% in group practice. Most of the GPs surveyed (60%) had been in practice for more than 10 years, 30% for 5-10 years and 10% were in practice for less than 5 years. Of GPs surveyed, 55% saw an average of more than 20 patients per week, 35% about 10-20 patients and 10% less than 10 patients per week. Of GPs surveyed, 65% would arrange an X-ray, 55% would arrange a blood test, mostly serum uric acid, rheumatoid factor and erythrocyte sedimentation rate. Pharmacological management consists of first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs) (61%), analgesics (35%) or a combination of the two (4%). Non-pharmacological management consisted of advice on exercise (27%), weight reduction (33%) and referral to physiotherapy (10%). Of GPs surveyed, 85% prescribed some form of complementary medications, 60% prescribed glucosamine sulphate, 21% chondroitin sulphate, 11% cod liver oil and 9% evening primrose oil. Only 10% of GPs surveyed perform intra-articular injections.
Conclusion: The data suggest that in the primary care setting, the majority of GPs over-investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesics and NSAIDs. The use of physiotheraphy and non-drug approaches were significantly under-utilized. There is a need to further educate GPs in the management of OA.

Matched MeSH terms: Uric Acid
Fulltext A pilot study of the primary care management of knee osteoarthritis in the Northern States of Malaysia.

Arshad, A., Rashid, R.

International Medical Journal Malaysia, 2008;7(2):31-36.
MyJurnal

Introduction: Primary care management of knee osteoarthritis OA has received little attention in the scientific literature and the main reason of this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting. Materials and Methods: A cross sectional survey of 100 randomly selected general practitioners (GPs) in the northern states of Malaysia (Kedah, Perlis, Pulau Pinang) was undertaken using questionnaires. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment of OA. They were also asked their usage of conventional and complementary medication. Results: 80 (80%) GPs responded to the questionnaires sent. 85% of GPs were in solo practice and 15% in group practice. Most of the GPs surveyed (69%) were in practice for more than 10 years, 21% in 5- 10 years and 10% were in practice for less than 5 years. 65% GPs surveyed see an average of more than 20 patients per week, 25% see about 10- 20 patients and 10% see less than 10 patients per week. 75% of GPs surveyed would arrange an X-ray. 65% of GPs surveyed will arrange a blood test, mostly serum uric acid, rheumatoid factor and ESR. Pharmacological management consists of first line treatment with analgesics (32%), NSAIDs (59%) or a combination of the two (4%). Non-pharmacological management consist of advise an exercise (37%), weight reduction (23%) and referral to physiotherapy (8%). 89% of GPs surveyed prescribed some form of complementary medications. 68% prescribed glucosamine sulphate, 29% chondroitin sulphate, 18% cod liver oil, 12% evening primrose oil. Only 5% of GPs surveyed perform intra- articular injection. Conclusion: The data suggest that in the primary care, majority of GP over investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesic and NSAIDs. The use of physiotherapy and non drug approach were enormously under-utilized. There is a need to further educate GPs in the management of OA.

Matched MeSH terms: Uric Acid
A simple and sensitive fluorescence based biosensor for the determination of uric acid using H2O2-sensitive quantum dots/dual enzymes

Azmi NE, Ramli NI, Abdullah J, Abdul Hamid MA, Sidek H, Abd Rahman S, et al.

Biosens Bioelectron, 2015 May 15;67:129-33.
PMID: 25113659 DOI: 10.1016/j.bios.2014.07.056

A novel optical detection system consisting of combination of uricase/HRP-CdS quantum dots (QDs) for the determination of uric acid in urine sample is described. The QDs was used as an indicator to reveal fluorescence property of the system resulting from enzymatic reaction of uricase and HRP (horseradish peroxidase), which is involved in oxidizing uric acid to allaintoin and hydrogen peroxide. The hydrogen peroxide produced was able to quench the QDs fluorescence, which was proportional to uric acid concentration. The system demonstrated sufficient activity of uricase and HRP at a ratio of 5U:5U and pH 7.0. The linearity of the system toward uric acid was in the concentration range of 125-1000 µM with detection limit of 125 µM.

Matched MeSH terms: Uric Acid/isolation & purification*; Uric Acid/urine; Uric Acid/chemistry
Fulltext Xanthine oxidase inhibitory activity from potential Malaysian medicinal plant as remedies for gout

Azmi SMN, Jamal P, Amid A

International Food Research Journal, 2012;19(1):159-165.
MyJurnal

Malaysia has a rich diversity of medicinal plants and some of them inhibit xanthine oxidase (XO), which can be introduced as new natural sources of gout medication and a substitute for synthetic xanthine oxidase inhibitors (XOI). The degree of XO inhibitory activity was determined by measuring the absorbance spectrophotometrically at 295 nm, which is associated with uric acid formation. Our preliminary screening study had employed the use of distilled water, 70% methanol and absolute ethanol to extract XOI from twenty parts of five plant species, namely, Averrhoa carambola, Carica papaya, Dimocarpus longan malesianus, Manilkara zapota and Salacca zalacca. These plants were selected based on their frequent medicinal usages by local folks. The results have shown that an aqueous extract of Carica papaya mature leaves has promising activity to inhibit XO up to 75.68 ± 0.1%. Statistical experimental design were employed to optimize the selected sample (dried Carica papaya leaves: distilled water) on extraction of XOI and the maximum XOI percentage of 86.93 ± 1.9% was obtained, which exhibited only 6.76% less than the activity exhibited by allopurinol (93.69 ± 0.2%), a commercial XOI. The comparison was made between allopurinol and optimized extract on the basis of IC50concentrations. Allopurinol showed IC50 value of 3.74 μg/ml that is considerably lower as compared to the optimized sample (4.33 μg/ml).

Matched MeSH terms: Uric Acid
Fenofibrate and dipyridamole treatments in low-doses either alone or in combination blunted the development of nephropathy in diabetic rats

Balakumar P, Varatharajan R, Nyo YH, Renushia R, Raaginey D, Oh AN, et al.

Pharmacol Res, 2014 Dec;90:36-47.
PMID: 25263930 DOI: 10.1016/j.phrs.2014.08.008

Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins. Hematoxylin-eosin, periodic acid Schiff and Masson trichrome staining confirmed renal pathological changes in diabetic rats that included glomerular capsular wall distortion, mesangial cell expansion, glomerular microvascular condensation, tubular damage and degeneration and fibrosis. Low-dose fenofibrate (30mg/kg, p.o., 4 weeks) and low-dose dipyridamole (20mg/kg, p.o., 4 weeks) treatment either alone or in combination considerably reduced renal structural and functional abnormalities in diabetic rats, but without affecting the elevated glucose level. Fenofibrate, but not dipyridamole, significantly prevented the lipid alteration and importantly the uric acid elevation in diabetic rats. Lisinopril (5mg/kg, p.o., 4 weeks, reference compound), prevented the hyperglycemia, lipid alteration and development of diabetic nephropathy. Lipid alteration and uric acid elevation, besides hyperglycemia, could play key roles in the development of nephropathy. Low-doses of fenofibrate and dipyridamole treatment either alone or in combination markedly prevented the diabetes-induced nephropathy. Their combination was as effective as to their individual treatment, but not superior in preventing the development of diabetic nephropathy.

Matched MeSH terms: Uric Acid/blood
Effects of pre and post-treatments with dipyridamole in gentamicin-induced acute nephrotoxicity in the rat

Balakumar P, WitnessKoe WE, Gan YS, JemayPuah SM, Kuganesswari S, Prajapati SK, et al.

Regul Toxicol Pharmacol, 2017 Mar;84:35-44.
PMID: 27993652 DOI: 10.1016/j.yrtph.2016.12.007

This study investigated the pretreatment and post-treatment effects of dipyridamole (20 mg/kg/day, p.o.) in gentamicin-induced acute nephrotoxicity in rats. Rats were administered gentamicin (100 mg/kg/day, i.p.) for 8 days. Gentamicin-administered rats exhibited renal structural and functional changes as assessed in terms of a significant increase in serum creatinine and urea and kidney weight to body weight ratio as compared to normal rats. Renal histopathological studies revealed a marked incidence of acute tubular necrosis in gentamicin-administered rats. These renal structural and functional abnormalities in gentamicin-administered rats were accompanied with elevated serum uric acid level, and renal inflammation as assessed in terms of decrease in interleukin-10 levels. Dipyridamole pretreatment in gentamicin-administered rats afforded a noticeable renoprotection by markedly preventing renal structural and functional abnormalities, renal inflammation and serum uric acid elevation. On the other hand, dipyridamole post-treatment did not significantly prevent uric acid elevation and renal inflammation, and resulted in comparatively less protection on renal function although it markedly reduced the incidence of tubular necrosis. In conclusion, uric acid elevation and renal inflammation could play key roles in gentamicin-nephrotoxicity. Dipyridamole pretreatment markedly prevented gentamicin-induced acute nephrotoxicity, while its post-treatment resulted in comparatively less renal functional protection.

Matched MeSH terms: Uric Acid/blood
Fulltext Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice

Bao R, Liu M, Wang D, Wen S, Yu H, Zhong Y, et al.

Front Pharmacol, 2019;10:1464.
PMID: 31920654 DOI: 10.3389/fphar.2019.01464

Background:Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia. The stems are traditionally used for the treatment of sexual insufficiency, fever, hypertension, and malaria. Furthermore, it has antidiabetic and anticancer activities. Recently, it has been reported to reduce uric acid, but the mechanism is unclear. Hypothesis/Purpose: The aim of this study is to explore the effect and mechanism of E. longifolia stem 70% ethanol extract (EL) and its active compounds on uric acid excretion. Study Design and Methods: Potassium oxonate (PO) induced hyperuricemia rats model and adenine-PO induced hyperuricemia mice model were used to evaluate the effects of EL. Ultraperformance liquid chromatography was used to determine the levels of plasma or serum uric acid and creatinine. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and western blot was applied to detect protein expression levels of uric acid transporters. Effects of constituents on urate uptake were tested in hURAT1-expressing HEK293T cells. Results: EL significantly reduced serum and plasma uric acid levels at dosages of 100, 200, and 400 mg/kg in hyperuricemia rats and mice, increased the clearance rate of uric acid and creatinine, and improved the renal pathological injury. The protein expression levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 were down-regulated, while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treatment. The quassinoids isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells, and the effect of eurycomanol was further confirmed in vivo. Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.

Matched MeSH terms: Uric Acid
Composition of normal urine in students of the University of Malaya

Chandra N, Bhattathiry EP

Trop Geogr Med, 1967 Dec;19(4):300-3.
PMID: 5585976
Matched MeSH terms: Uric Acid/urine
Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action

Cheng LC, Murugaiyah V, Chan KL

J Ethnopharmacol, 2015 Dec 24;176:485-93.
PMID: 26593216 DOI: 10.1016/j.jep.2015.11.025

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, and Sidha systems, as well as Traditional Chinese Medicine (TCM) for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling.
AIM OF THE STUDY: The present study aims to investigate the antihyperuricemic effect of the L. nodiflora methanol extract, fractions, and chemical constituents and their mechanism of action in the rat model.
MATERIALS AND METHODS: The mechanisms were investigated by performing xanthine oxidase inhibitory, uricosuric, and liver xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitory studies in potassium oxonate- and hypoxanthine-induced hyperuricemic rats. The plant safety profile was determined using acute toxicity study. The molecular docking of the active compound to the xanthine oxidase was simulated using computer aided molecular modeling analysis.
RESULTS: Oral administration of methanol extract showed a dose-dependent reduction effect on the serum uric acid level of hyperuricemic rats. F3 was the most potent fraction in lowering the serum uric acid level of hyperuricemic rats. Bioactivity-guided purification of F3 afforded two phenylethanoid glycosides, arenarioside (1) and verbascoside (2) and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). The highest serum uric acid reduction effect was exhibited by 3 (66.94%) in hyperuricemic rats, followed by 5 (55.97%), 4 (49.16%), 2 (29.03%), and 1 (22.08%) at 0.2 mmol/kg. Dose-response investigation on 3 at doses of 0.05, 0.1, and 0.3 mmol/kg produced a significant dose-dependent reduction on the serum uric acid level of hyperuricemic rats. Repeated administration of F3 or 3 to the hyperuricemic rats for 10 continuous days resulted in a significant and progressive serum uric acid lowering effect in hyperuricemic rats. In contrast, methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. In addition, F4 significantly increased the uric acid excretion of hyperuricemic rats at 200mg/kg. No toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3.
CONCLUSION: The potential application of L. nodiflora against hyperuricemia in the animal in accordance with its traditional uses has been demonstrated in the present study for the first time. The antihyperuricemic effect possessed by L. nodiflora was contributed mainly by liver XOD/XDH inhibitory activities and partially by uricosuric effect. Flavonoids mainly accountable for the uric acid lowering effect of L. nodiflora through the inhibition of XOD/XDH activities.
KEYWORDS: Antihyperuricemic; Hypoxanthine-induced hyperuricemic rat; Lippia nodiflora; Liver xanthine oxidase and xanthine dehydrogenase; Serum uric acid; Uric acid excretion

Matched MeSH terms: Uric Acid/blood
Fulltext Significant association between parathyroid hormone and uric acid level in men

Chin KY, Nirwana SI, Ngah WZ

Clin Interv Aging, 2015;10:1377-80.
PMID: 26346636 DOI: 10.2147/CIA.S90233

Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH) and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men.

Matched MeSH terms: Uric Acid/blood*

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