Lithospermic acid as a novel xanthine oxidase inhibitor has anti-inflammatory and hypouricemic effects in rats

2008 ◽  
Vol 176 (2-3) ◽  
pp. 137-142 ◽  
Author(s):  
Xiaoyu Liu ◽  
Ruohua Chen ◽  
Yanjun Shang ◽  
Binghua Jiao ◽  
Caiguo Huang
Author(s):  
Pascal Richette

The general goals of gout therapy are to manage acute flares and to prevent recurrences and prevent or reverse the complications of urate deposition by lowering urate levels. The choice of drug should be made on the basis of the patient’s co-morbidities, other medications, and side effect profile. Treatment of flares can be achieved with non-steroidal anti-inflammatory drugs, colchicine, or corticosteroids (systemic or intra-articular). Interleukin-1 blockers could become an alternative in patients contraindicated for traditional anti-inflammatory agents. Lowering of urate levels below monosodium urate (MSU) saturation point with both a non-pharmacological and pharmacological approach allows to dissolve MSU crystals and to cure gout. Serum urate (SUA) levels should be maintained below 6 mg/dL (360 μ‎mol/L) or below 5 mg/dL (300 μ‎mol/L) in patients with severe gout to facilitate faster dissolution of crystals. Urate-lowering therapy (ULT) should be initiated close to the first diagnosis of gout. Allopurinol and febuxostat are the most widely used xanthine oxidase inhibitors to lower SUA levels. If the SUA target cannot be reached by these agents, uricosurics are indicated, either alone or in combination with a xanthine oxidase inhibitor. In patients with severe tophaceous gout in whom the SUA target cannot be reached with any other available drug, pegloticase is indicated. Since ULT initiation may trigger acute attacks of gout, prophylaxis with an anti-inflammatory agent is recommended, mostly with low-dose colchicine. Of note, patient education, appropriate lifestyle advice, and treatment of comorbidities are also important parts of the management of patients with gout.


2019 ◽  
Vol 97 (7) ◽  
pp. 611-622 ◽  
Author(s):  
Mohammed M. Heikal ◽  
Ahmed A. Shaaban ◽  
Wagdi F. Elkashef ◽  
Tarek M. Ibrahim

Febuxostat, a highly potent xanthine oxidase inhibitor with an antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. The aim of this study was to test the potential antioxidant and anti-inflammatory effects of febuxostat and (or) stopping a high-fat diet on the biochemical parameters in rabbits with hyperlipidemia induced by a high-fat diet. Male New Zealand rabbits were distributed into 3 groups: a normal control group fed standard chow for 12 weeks and 2 other groups fed a high-fat diet with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks, one high-fat diet group received 0.5% carboxymethyl cellulose, whereas the other group was treated with febuxostat (2 mg/kg per day p.o.). Febuxostat significantly lowered low-density lipoprotein cholesterol (“bad” cholesterol) compared to the untreated group (high-fat diet group). Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, proinflammatory cytokines, and enhancing antioxidant enzyme activity. Stopping the hyperlipidemic diet in the high-fat diet group did not show improvement. These findings indicate the antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping a hyperlipidemic diet without treatment is not sufficient once injury has occurred.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 549-P
Author(s):  
HIROKI MIZUKAMI ◽  
REMINA KOYAMA ◽  
KAZUHISA TAKAHASHI ◽  
SHO OSONOI ◽  
SAORI OGASAWARA ◽  
...  

2020 ◽  
Vol 20 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Mahnaz Arian ◽  
Mina AkbariRad ◽  
Ahmad Bagheri Moghaddam ◽  
Abdollah Firoozi ◽  
Mohammad Jami

: Allopurinol is an FDA -Approved xanthine oxidase inhibitor, which is effective in the treatment of gout, hyperuricemia and uremic kidney stones in patients with an increased level of uric acid excretion. Xanthine oxidase acts by converting hypoxanthine and xanthine into uric acid, and therefore its inhibition results in decreased production of uric acid. The most common side effects of this medication are as follows: maculopapular rashes, hives, itching, headache, dizziness, abnormal hair loss, fever and hypersensitivity reaction. Case Presentation: This report represents a case of drug-induced meningitis of a senile man who ended up in the ICU due to the remarkably reduced state of consciousness.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Saito ◽  
Kenichi Tanaka ◽  
Tsuyoshi Iwasaki ◽  
Akira Oda ◽  
Shuhei Watanabe ◽  
...  

AbstractAs previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.


1988 ◽  
Vol 12 (1) ◽  
pp. 209-217 ◽  
Author(s):  
James M Kinsman ◽  
Charles E Murry ◽  
Vincent J Richard ◽  
Robert B Jennings ◽  
Keith A Reimer

2010 ◽  
Vol 77 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Torben Larsen ◽  
Kasey M Moyes

The primary objective of this study is to validate a new fast method for determination of uric acid in milk. The method is based on an enzymatic-fluorometric technique that requires minimal pre-treatment of milk samples. The present determination of uric acid is based on the enzymatic oxidation of uric acid to 5-hydroxyisourate via uricase where the liberated hydrogen peroxide reacts with 10-acetyl-3,7-dihydroxyphenoxazine via peroxidase and the fluorescent product, resorufin, is measured fluorometrically. Fresh composite milk samples (n=1,072) were collected from both Jersey (n=38) and Danish Holstein (n=106) cows from one local herd. The average inter- and intra-assay variations were 7·1% and 3·0%, respectively. Percent recovery averaged 103·4, 107·0 and 107·5% for samples spiked with 20, 40 or 60 μmof standard, respectively, with a correlation (r=0·98;P<0·001) observed between the observed and expected uric acid concentrations. A positive correlation (r=0·96;P<0·001) was observed between uric acid concentrations using the present method and a reference assay. Storage at 4°C for 24 h resulted in lower (P<0·01) uric acid concentrations in milk when compared with no storage or samples stored at −18°C for 24 h. Addition of either allopurinol (a xanthine oxidase inhibitor) or dimethylsulfoxide (a solvent for allopurinol) did not affect milk uric acid concentrations (P=0·96) and may indicate that heat treatment before storage and analysis was sufficient to degrade xanthine oxidase activity in milk. No relationship was observed between milk uric acid and milk yield and milk components. Authors recommend a single heat treatment (82°C for 10 min) followed by either an immediate analysis of fresh milk samples or storage at −18°C until further analysis.


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