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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Fulltext Suggestive evidence of SIc2a9 polymorphisms association in gouty malay males
    Mahfudzah A, Nazihah MY, Wan Syamimee WG, Huay, Lin T, Wan Rohani WT
    International Medical Journal Malaysia, 2015;14(2):35-40.
    MyJurnal
    Introduction: Solute carrier family 2, member 9 (SLC2A9) is thought to be an important urate transporter that influences the excretion and reabsorption of serum uric acid, thus has a strong effect on serum urate and risk of gout. SLC2A9 polymorphisms have been extensively studied in various populations in association with gout development. Our aim was to test for association of SLC2A9 SNPs with gout in Malay males.
    Methods: 78 gouty patients and 82 normal subjects were recruited and genotyped for rs3733591, rs5028843 and rs11942223 using PCR-RFLP technique. Single association and haplotype association analyses were conducted using SHEsis online software.
    Results: rs3733591 and rs5028843 showed association with gout with p value of 0.020 and 0.036, respectively, whilst rs11942223 yielded no association with p value of 0.08 with trend towards susceptibility projecting by OR=3.547, 3.667 and 2.732, respectively. It is noteworthy that haplotype 1/1/1 conferred protection in gout with p value 0.004 (OR=0.324 [0.147-0.716]).
    Conclusion: This study might suggest an evidence of association of SLC2A9 SNPs with gout among Malay males.
    KEYWORDS: Gout, SLC2A9, Malay males
    Study site: Medical Specialist Clinic at Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia
    Matched MeSH terms: Uric Acid
  7. 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
  8. 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
  9. Fulltext Association between elevated carotid intima-media thickness and serum uric acid levels among patients with essential hypertension in primary care setting in Sungai Buloh, Malaysia
    Mohd Nasir MZ, Malek KA, Isa MR, Hamdan MF, Abdul Kadir RF, Ahmad F, et al.
    Int J Clin Pract, 2021 Sep;75(9):e14445.
    PMID: 34105862 DOI: 10.1111/ijcp.14445
    AIMS: Our study aimed to investigate the association between elevated carotid-intima media thickness (CIMT) and serum uric acid (SUA) levels in hypertensive patients attending primary care clinics in Sungai Buloh, Malaysia.

    METHODS: We conducted a cross-sectional study on 140 hypertensive patients attending outpatient follow-up in two primary care clinics in Sungai Buloh, Malaysia, using a convenient sampling method. SUA levels were measured and divided into four quartiles. Two radiologist specialists performed B mode ultrasonography to assess the thickness of the right and left carotid intima media in all participants.

    RESULTS: Participants' mean SUA level was 355.75 ± 0.13. Their mean age was 53.44 (± 9.90), with a blood pressure control of 137.09 ± 13.22/81.89 ± 8.95. Elevated CIMT taken at ≥75th percentile was 0.666 for the left and 0.633 for the right common carotid arteries. By using a hierarchical method of multiple logistic regression, compared with the first quartile of the SUA level as reference group, the odd of elevated CIMT in quartile 4 in the common carotid artery was (OR = 2.00; 95% CI = 0.64-6.27, P = .576) for the right and (OR = 0.62; 95% CI = 0.20-2.00, P = .594) for the left. Waist circumference (P = .001), body mass index (P = .013), triglycerides (P 

    Matched MeSH terms: Uric Acid
  10. A survey on the management of gout in Malaysia
    Yeap SS, Goh EM, Gun SC
    Int J Rheum Dis, 2009 Dec;12(4):329-35.
    PMID: 20374371 DOI: 10.1111/j.1756-185X.2009.01431.x
    AIM: The aim of this study was to ascertain the management of gout by doctors in Malaysia.
    METHODS: A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic.
    RESULTS: A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia.
    CONCLUSIONS: In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines
    Matched MeSH terms: Uric Acid/blood
  11. Clinical significance of SLC2A9/GLUT9 rs11722228 polymorphisms in gout
    Das Gupta E, Sakthiswary R, Lee SL, Wong SF, Hussein H, Gun SC
    Int J Rheum Dis, 2018 Mar;21(3):705-709.
    PMID: 27456670 DOI: 10.1111/1756-185X.12918
    AIM: The main objective of this study is to elucidate the clinical significance of the SLC2A9/GLUT9 rs11722228 polymorphism among male gout patients.
    METHOD: We consecutively recruited all newly diagnosed male gout patients who were treatment-naive from the rheumatology outpatient clinics of two Malaysian hospitals. Age-matched healthy male adults were employed as controls. All subjects were tested for the SLC2A9/GLUT9 rs11722228 genotypes, serum uric acid (SUA), urine uric acid and creatinine levels. All gout subjects were examined for the presence of tophi and sonographically screened for renal calculi.
    RESULTS: A total of 73 male gout patients and 73 age-matched healthy male adults were recruited in this study. The genotypic frequencies of SLC2A9/GLUT9 rs1172228 did not differ significantly between the gout cases and the healthy controls. The gout subjects with the CC genotype had significantly higher SUA levels (P = 0.002), family history of gout (P < 0.050) and the occurrence of renal calculi (P = 0.026). The SUA-adjusted odds ratios (OR) of the occurrence of renal calculi in the CC genotype (OR = 1 [reference]) was significantly higher than the CT genotype (OR = 0.338, 95%CI: 0.141-0.813) and the TT genotype (OR = 0.271, 95%CI: 0.086-0.854).
    CONCLUSIONS: The genotypic distribution of SLC2A9/GLUT9 rs1172228 in male gout patients did not differ significantly from that of healthy male controls. However, the CC genotype in gout had significant associations with higher levels of SUA, renal calculi and a positive family history of gout.
    Study site: Rheumatology clinic, Tuanku Jaafar Hospital, Malaysia and Putrajaya Hospital, Malaysia
    Matched MeSH terms: Uric Acid/blood; Uric Acid/urine
  12. Discrimination of dopamine by an electrode modified with negatively charged manganese dioxide nanoparticles decorated on a poly(3,4 ethylenedioxythiophene)/reduced graphene oxide composite
    Promsuwan K, Soleh A, Saisahas K, Saichanapan J, Kanatharana P, Thavarungkul P, et al.
    J Colloid Interface Sci, 2021 Sep;597:314-324.
    PMID: 33872888 DOI: 10.1016/j.jcis.2021.03.162
    A unique nanocomposite was fabricated using negatively charged manganese dioxide nanoparticles, poly (3,4-ethylenedioxythiophene) and reduced graphene oxide (MnO2/PEDOT/rGO). The nanocomposite was deposited on a glassy carbon electrode (GCE) functionalized with amino groups. The modified GCE was used to electrochemically detect dopamine (DA). The surface morphology, charge effect and electrochemical behaviours of the modified GCE were characterized by scanning electron microscopy, energy dispersive X-ray analysis (EDX), cyclic voltammetry and electrochemical impedance spectroscopy, respectively. The MnO2/PEDOT/rGO/GCE exhibited excellent performance towards DA sensing with a linear range between 0.05 and 135 µM with a lowest detection limit of 30 nM (S/N = 3). Selectivity towards DA was high in the presence of high concentrations of the typical interferences ascorbic acid and uric acid. The stability and reproducibility of the electrode were good. The sensor accurately determined DA in human serum. The synergic effect of the multiple components of the fabricated nanocomposite were critical to the good DA sensing performance. rGO provided a conductive backbone, PEDOT directed the uniform growth of MnO2 and adsorbed DA via pi-pi and electrostatic interaction, while the negatively charged MnO2 provided adsorption and catalytic sites for protonated DA. This work produced a promising biosensor that sensitively and selectively detected DA.
    Matched MeSH terms: Uric Acid
  13. 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
  14. Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents
    Murugaiyah V, Chan KL
    J Ethnopharmacol, 2009 Jul 15;124(2):233-9.
    PMID: 19397979 DOI: 10.1016/j.jep.2009.04.026
    ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.
    AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.
    MATERIAL AND METHODS: The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.
    RESULTS: Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.
    CONCLUSIONS: The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.
    Matched MeSH terms: Uric Acid/urine*
  15. 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*
  16. Phyllanthus niruri leaves aqueous extract improves kidney functions, ameliorates kidney oxidative stress, inflammation, fibrosis and apoptosis and enhances kidney cell proliferation in adult male rats with diabetes mellitus
    Giribabu N, Karim K, Kilari EK, Salleh N
    J Ethnopharmacol, 2017 Jun 09;205:123-137.
    PMID: 28483637 DOI: 10.1016/j.jep.2017.05.002
    ETHNOPHARMACOLOGICAL RELEVANCE: Phylanthus niruri has been used to treat ailments related to the urogenital organs. In this study, this herb was hypothesized to help to ameliorate kidney disease in diabetes mellitus (DM).

    AIMS: To investigate P. niruri leaves aqueous extract (PN) effects on kidney functions, histopathological changes and levels of oxidative stress, inflammation, fibrosis, apoptosis and proliferation in DM.

    METHODS: PN was orally administered to streptozotocin-nicotinamide-induced male diabetic rats for 28 days. At the end of the treatment, fasting blood glucose (FBG) and kidney functions were measured. Kidney somatic index, histopathological changes and levels of RAGE, Nrf2, oxidative stress markers (TBARS, SOD, CAT and GPx), inflammatory markers (NFkβ-p65, Ikk-β, TNF-α, IL-1β and IL-6), apoptosis markers (caspase-3, caspase-9 and Bax), fibrosis markers (TGF-β1, VEGF and FGF-1) and proliferative markers (PCNA and Ki-67) were determined by biochemical assays, qPCR, Western blotting, immunohistochemistry or immunofluorescence.

    RESULTS: Administration of PN helps to maintain near normal FBG, creatinine clearance (CCr), blood urea nitrogen (BUN), BUN/Cr ratio, serum electrolytes, uric acid and urine protein levels in DM. Decreased RAGE, TBARS and increased Nrf2, SOD-1, CAT and GPx-1 were observed in PN-treated diabetic rat kidneys. Expression of inflammatory, fibrosis and apoptosis markers in the kidney reduced but expression of proliferative markers increased following PN treatment. Lesser histopathological changes were observed in the kidney of PN-treated diabetic rats.

    CONCLUSION: PN helps to preserve near normal kidney function and prevents histopathological changes via ameliorating oxidative stress, inflammation, fibrosis and apoptosis while enhancing proliferation of the kidney in DM.

    Matched MeSH terms: Uric Acid; Thiobarbituric Acid Reactive Substances
  17. Fabrication of low-cost sustainable electrocatalyst: a diagnostic tool for multifunctional disorders in human fluids
    Sinduja B, Gowthaman NSK, John SA
    J Mater Chem B, 2020 10 28;8(41):9502-9511.
    PMID: 32996975 DOI: 10.1039/d0tb01681k
    In purine metabolism, the xanthine oxidoreductase enzyme converts hypoxanthine (HXN) to xanthine (XN) and XN to uric acid (UA). This leads to the deposition of UA crystals in several parts of the body and the serum UA level might be associated with various multifunctional disorders. The dietary intake of caffeine (CF) and ascorbic acid (AA) decreases the UA level in the serum, which leads to cellular damage. Hence, it is highly needed to monitor the UA level in the presence of AA, XN, HXN, and CF and vice versa. Considering this sequence of complications, the present paper reports the fabrication of an electrochemical sensor using low-cost N-doped carbon dots (CDs) for the selective and simultaneous determination of UA in the presence of AA, XN, HXN, and CF at the physiological pH. The colloidal solution of CDs was prepared by the pyrolysis of asparagine and fabricated on a GC electrode by cycling the potential from -0.20 to +1.2 V in a solution containing CDs and 0.01 M H2SO4. Here, the surface -NH2 functionalities of CDs were used to make a thin film of CDs on the GC electrode. FT-IR spectroscopy confirmed the involvement of the -NH2 group in the formation of the CD film. HR-TEM analysis depicts that the formed CDs showed spherical particles with a size of 1.67 nm and SEM analysis exhibits the 89 nm CD film on the GC electrode surface. The fabricated CD film was successfully used for the sensitive and selective determination of UA. The determination of UA was achieved selectively in a mixture consisting of AA, XN, HXN, and CF with 50-fold high concentration. The CDs-film fabricated electrode has several benefits over the bare electrode: (i) well-resolved oxidation peaks for five analytes, (ii) boosted sensitivity, (iii) shifted oxidation as well as on-set potentials toward less positive potentials, and (iv) high stability. The practical utility of the present sensor was tested by simultaneously determining the multifactorial disorders-causing agents in human fluids. The electrocatalyst developed in the present study is sustainable and can be used for multiple analyses; besides, the electrochemical method used for the fabrication of the CD film is environmentally benign.
    Matched MeSH terms: Uric Acid/blood*
  18. Foetal and maternal outcomes in hyperuricaemia pre-eclampsia patients in Hospital Universiti Sains Malaysia
    Jummaat F, Adnan AS, Ab Hamid SA, Hor JN, Nik Mustofar NN, Muhammad Asri NA, et al.
    J Obstet Gynaecol, 2021 Jan;41(1):38-43.
    PMID: 33124936 DOI: 10.1080/01443615.2019.1679731
    Preeclampsia patients have frequently been found to experience hyperuricaemia and this may result in poor outcomes compared to those with normal uric acid levels. This study aimed to determine the relationship of hyperuricaemia in pre-eclampsia patients with foetal and maternal outcomes. This prospective cohort study involved 79 patients in a tertiary centre from year 2016 to 2018. Blood samples were taken antenatally and at the 6th week, post-delivery for renal function including serum uric acid level. Our findings indicate that there was a higher incidence of poor maternal and foetal outcomes in the hyperuricaemia group than the normal uric acid group. Serum uric acid has been shown to be a significant predictor for low birth weight and premature delivery in preeclampsia patients. It was also found that there was a significant negative correlation between uric acid level and antenatal creatinine clearance (rs = -0.338, p = .002). The assessment of the serum uric acid level seems to be important to ensure better outcomes in patients with preeclampsia.Impact statementWhat is already known on this subject? Preeclampsia is a serious pregnancy-related complication and remains as one of the most important cause of maternal and foetal morbidity and mortality, affecting 2-8% in all pregnancy. Many studies have established the association between hyperuricaemia and preeclampsia. Besides, numerous studies have found that hyperuricaemia contributed to adverse maternal and foetal outcomes.What the results of this study add? There was a significant increase in adverse foetal and maternal outcomes in the hyperuricaemia group compared to the normal uric acid group. This study revealed that serum uric acid remains a significant predictor for low birth weight and premature delivery in preeclampsia patients.What the implications are of these findings for clinical practice and/or further research? Hyperuricaemia does not merely become an indicator for the severity of disease in preeclampsia patients but also indicates adverse foetal outcomes. Large population-based studies are required to establish the absolute maternal and foetal outcomes in patients with hyperuricaemia. Besides, further studies are recommended on long-term implication of hyperuricaemia which is not limited to only during antenatal period.
    Matched MeSH terms: Uric Acid/blood
  19. Fulltext A single-centre experience of febuxostat as a second-line urate-lowering therapy
    Ong SG, Ding HJ
    Malays Fam Physician, 2021 Mar 25;16(1):50-55.
    PMID: 33948142 DOI: 10.51866/oa0892
    Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate-lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease.

    Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.

    Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.

    Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

    Matched MeSH terms: Uric Acid
  20. Fulltext Association and interaction effect between VEGF receptor-2 (VEGFR-2) gene polymorphisms and dietary pattern on blood uric acid in Malays and Indians
    Roseline YW, Shidoji Y, Hon WM, Masaki M
    Malays J Nutr, 2012 Dec;18(3):307-17.
    PMID: 24568071 MyJurnal
    INTRODUCTION: Gout and hyperuricaemia attributed to genetic and lifestyle factors have been associated with several chronic diseases. This study aimed to determine the association and interaction effects between vascular endothelial growth factor receptor-2 (VEGFR-2) gene polymorphisms (rs1870377 and rs2071559) and dietary patterns on blood uric acid in Malay and Indian adults.
    METHODS: Dietary intakes of 153 Malays and 177 Indians were obtained using a food frequency questionnaire for the construction of dietary patterns using factor analysis. Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan probes. Anthropometric measurements, body mass index (BMI) and blood pressure and biomarkers, uric acid, glycated haemoglobin A1c (HbA1c), and blood lipids were determined.
    RESULTS: There were significant differences in the mean values for HbA1c (41±-12 vs 45±-8 mmol/mol, p<0.001) and blood lipids levels (p<0.05) between Malays and Indians. Significant correlations were obtained between uric acid with selected blood lipids (p<0.05) and BMI in Malays (r=0.362, p<0.001) and Indians (r=0.212, p<0.01). Four dietary patterns were extracted from dietary intakes of all subjects: ‘Vegetables diet’; ‘Fruits diet’ (FD); ‘Animal protein and rice diet’; and ‘Fast foods and preserved foods diet’. There were no significant associations between dietary patterns (p=0.054-0.609) and VEGFR-2 gene polymorphisms (p=0.348-0.778) with uric acid. In Malay subjects, the interaction of rs2071559 and FD had a borderline effect (p=0.05) on blood uric acid after adjusting for potential confounders.
    CONCLUSION: The associations and gene-diet interactions involving VEGFR-2 gene polymorphisms and FD on uric acid provide new information on gout and hyperuricaemia risks in Malays.
    Keywords: Gene-diet interaction, VEGFR-2 gene polymorphisms, dietary pattern, uric acid, Malaysians
    Matched MeSH terms: Uric Acid/blood*
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