Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypouricemic effect of benzbromarone has been investigated in six subjects. Benzbromarone increased urate: creatinine by 371 per cent over control values at two to four hours after administration. Over a 24 hour period, the mean serum uric acid decreased from a control value of 7.8 +/- 0.8 to 4.3 +/- 0.6 mg/dl. This uricosuric effect was completely reversed by pyrazinamide, partially inhibited by acetylsalicyclic acid and sulfinpyrazone, and was not accompanied by an elevation of the creatinine clearance or an inhibition of urate binding to plasma protein. In vitro studies showed only 22 per cent inhibition of urate binding by benzbromarone five muM, a concentration which is transiently reached in man. Kinetic studies of human liver xanthine oxidase demonstrated non-competitive inhibition with variable hypoxanthine and a Ki slope of 8.5 muM. The Ki slopes for benzarone and allopurinol were 19.0 muM and 0.05 muM respectively. There was no elevation of the urinary oxypurines following benzbromarone ingestion. These observations suggest that only the renal tubular activity of benzbromarone is relevant to its hypouricemic effects in man. (J Rheumatol 2: 437-445, 1975).
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PMID:The pharmacology of hypouricemic effect of benzbromarone. 120 75

The long-term efficacy and safety of benzbromarone were studied in 21 nontophaceous hyperuricemic men. Daily doses of 40 or 80 mg of micronized benzbromarone caused a rapid fall in plasma urate which was maintained throughout a study period that lasted up to 1 year. A concomitant marked increase in the clearance of urate indicated that benzbromarone is a potent uricosuric drug. Initial treatment was accompanied by transient hyperuricosuria, following which urinary uric acid reverted toward, but failed to reach completely, pretreatment values. Benzbromarone did not inhibit xanthine oxidase nor did it influence the activity of purine phosphoribosyl transferases. These observations suggest that benzbromarone has no direct effect upon purine metabolic pathways, but exerts its hypouricemic action solely by blocking tubular reabsorption of uric acid. Concomitant administration of aspirin interfered only slightly with the uricosuric properties of benzbromarone. No side effects directly attributable to the drug were observed.
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PMID:Clinical evaluation of benzbromarone: a new uricosuric drug. 125 99

Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC 1.2.1.37), an enzyme involved in the regulation of this pathway. We found that allopurinol is several times superior to benzbromarone in the lowering of allantoin production (if they are compared in terms of their relative therapeutic levels), and that probenecid had no effect on it.
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PMID:Inhibition of purine catabolism by benzbromarone in isolated rat liver cells. Comparison with allopurinol and probenecid. 317 70

In 2003, the uricosuric drug benzbromarone was withdrawn from the market. The first alternative drug of choice was the xanthine oxidase inhibitor allopurinol. The purpose was to (1) investigate the efficacy of allopurinol (standard dosage) compared with previous treatment with benzbromarone; and (2) investigate the combination therapy allopurinol-probenecid as an effective alternative treatment compared with previous benzbromarone treatment. A prospective, open study was carried out in a cohort of 51 gout patients who discontinued benzbromarone therapy because of market withdrawal. Patients were given 200-300 mg allopurinol (stage 1). When allopurinol failed to attain the target serum urate (sUr) levels <or=0.30 mmol/l, probenecid 1,000 mg/day was added (stage 2). Treatment with benzbromarone monotherapy (range: 100-200 mg/day; mean 138 mg/day) resulted in 92% of patients reaching target levels sUr <or= 0.30 mmol/l with a decrease of 61[11]% compared to baseline. In stage 1, 32 patients completed treatment with allopurinol monotherapy (range 200-300 mg/day; mean 256 mg/day), which resulted in 25% of patients attaining sUr target levels. Decrease in sUr levels was 36[11]%, which was significantly less compared to treatment with benzbromarone (p < 0.001). In stage 2, 14 patients received allopurinol-probenecid combination therapy, which resulted in 86% of patients attaining target sUr levels (after failure on allopurinol monotherapy), which was comparable to previous treatment with benzbromarone (p = 0.81). Decrease in sUr levels was 53[9]% (CI 95%: 48-58%), which was a non-significant difference compared to previous treatment with benzbromarone (p = 0.23). Benzbromarone is a very effective antihyperuricemic drug with 91% success in attainment of target sUr levels <or=0.30 mmol/l. Allopurinol 200-300 mg/day was shown to be a less potent alternative for most selected patients to attain target sUr levels (13% success). In patients failing on allopurinol monotherapy, the addition of probenecid proves to be an effective treatment strategy for attaining sUr target levels (86% success).
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PMID:Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients. 1730 59

Inulin, a group of dietary fibers, is reported to improve the metabolic disorders. In the present study, we investigated the effects of chicory inulin on serum metabolites of uric acid (UA), lipids, glucose, and abdominal fat deposition in quail model induced by a purine-rich diet. In this study, 60 male French quails were randomly allocated to five groups: CON (control group), MOD (model group), BEN (benzbromarone-treated group), CHI-H (high-dosage chicory inulin-treated group), and CHI-L (low-dosage chicory inulin-treated group). The serum UA level was significantly increased in the model group from days 7 to 28, as well as triglyceride (TG) and free fatty acid (FFA) increased later in the experimental period. The abdominal fat ratio was increased on day 28. Benzbromarone can decrease UA levels on days 14 and 28. The high and low dosage of chicory inulin also decreased serum UA levels on days 7, 14, and 28. The abdominal fat ratio, activity, and protein of acetyl-CoA carboxylase (ACC) were decreased in chicory inulin-treated groups. The activities of xanthine oxidase (XOD) and fatty acid synthase (FAS) were increased in the model group and decreased in the benzbromarone and chicory inulin groups. This study evaluated a quail model of induced hyperuricemia with other metabolic disorders caused by a high-purine diet. The results indicated that a purine-rich diet might contribute to the development of hyperuricemia, hypertriglyceridemia, and abdominal obesity. Chicory inulin decreased serum UA, TG, and abdominal fat deposition in a quail model of hyperuricemia by altering the ACC protein expression and FAS and XOD activities.
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PMID:Effects of chicory inulin on serum metabolites of uric acid, lipids, glucose, and abdominal fat deposition in quails induced by purine-rich diets. 2531 75

Allopurinol, an inhibitor of xanthine oxidase, reduces both plasma uric acid and oxidative stress and shows useful effects on some complications of diabetes. However, it is not defined which of the above mentioned properties are involved. Moreover, to the best of our knowledge no study has been done on the effects of allopurinol on diabetic retinopathy. In the present study, the effect of allopurinol on experimental diabetic retinopathy and its possible mechanism has been investigated. Thirty two rats were divided into four groups of eight rats each; (1) normal, (2) diabetic control, (3) diabetic + allopurinol (50 mg/kg.day), (4) diabetic + benzbromarone (10 mg/kg.day). Drugs were administered daily and orally from the day after diabetes induction for eight weeks. Thereafter retinal function and structure were evaluated by electroretinography and microscopic studies. Uric acid and oxidative stress biomarkers were measured biochemically. Diabetes significantly increased plasma uric acid and oxidative stress markers and reduced body weight and amplitude of electroretinogram (ERG) b-wave and oscillatory potentials. Treatment of diabetic rats with allopurinol caused a significant increase in the amplitude of ERG b-wave (87%) and decrease in blood sugar (20%), uric acid (49%), and 8-iso-prostaglandin F2a (56%), but had no effect on the number of retinal ganglionic cells and oscillatory potentials. Benzbromarone showed no significant effects on the considered parameters except the reduction of uric acid. Allopurinol improved the b-wave amplitude of diabetic rats. It seems that this beneficial effect is due to the reduction of oxidative stress rather than its effect on plasma uric acid.
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PMID:Can allopurinol improve retinopathy in diabetic rats? Oxidative stress or uric acid; which one is the culprit? 2897 78

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.
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PMID:Randomized, Open-Label, Cross-Over Comparison of the Effects of Benzbromarone and Febuxostat on Endothelial Function in Patients with Hyperuricemia. 3292 65