Non-purine selective xanthine oxidase inhibitor ameliorates glomerular endothelial injury in InsAkita diabetic mice

Endothelial dysfunction represents a predominant early feature of diabetes, rendering patients with diabetes prone to renal complications, e.g., proteinuria. Recent studies have indicated a possible role for xanthine oxidase (XO) in the pathogenesis of vascular dysfunctions associated with diabetes. In the present study, we investigated the contribution of XO activation on the progression of diabetic nephropathy in a mouse model using selective XO inhibitors. Male Ins2Akita heterozygous mice were used with wild-type mice as controls. Akita mice were treated with topiroxostat (Topi) or vehicle for 4 wk. Serum uric acid levels were significantly reduced in Akita + Topi mice compared with Akita + vehicle mice. The Akita + Topi group had a significant reduction in urinary albumin excretion compared with the Akita + vehicle group. Mesangial expansion, glomerular collagen type IV deposition, and glomerular endothelial injury (assessed by lectin staining and transmission electron microscopy) were considerably reduced in the Akita + topi group compared with the Akita + vehicle group. Furthermore, glomerular permeability was significantly higher in the Akita + vehicle group compared with the wild-type group. These changes were reduced with the administration of Topi. We conclude that XO inhibitors preserve glomerular endothelial functions and rescue compromised glomerular permeability, suggesting that XO activation plays a vital role in the pathogenesis of diabetic nephropathy.

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Beneficial Effects of Xanthine Oxidase Inhibitor, Topiloxostat, on Experimental Diabetic Neuropathy in Mice

Diabetes ◽

10.2337/db18-549-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 549-P

Author(s):

HIROKI MIZUKAMI ◽

REMINA KOYAMA ◽

KAZUHISA TAKAHASHI ◽

SHO OSONOI ◽

SAORI OGASAWARA ◽

...

Keyword(s):

Diabetic Neuropathy ◽

Xanthine Oxidase ◽

Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitor ◽

Beneficial Effects ◽

Experimental Diabetic Neuropathy

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Faculty Opinions recommendation of Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1046725.496732 ◽

2006 ◽

Author(s):

Klaus Ley

Keyword(s):

Xanthine Oxidase ◽

Knockout Mice ◽

Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitor ◽

Apoe Knockout Mice

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Allopurinol and Loss of Consciousness in a 78-old Year Man Suffering from Gout

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190128102039 ◽

2020 ◽

Vol 20 (2) ◽

pp. 253-256 ◽

Cited By ~ 1

Author(s):

Mahnaz Arian ◽

Mina AkbariRad ◽

Ahmad Bagheri Moghaddam ◽

Abdollah Firoozi ◽

Mohammad Jami

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Kidney Stones ◽

Oxidase Inhibitor ◽

Loss Of Consciousness ◽

Drug Induced ◽

Xanthine Oxidase Inhibitor ◽

Case Presentation ◽

Maculopapular Rashes ◽

Reduced State

: 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.

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Xanthine oxidase inhibitors are associated with reduced risk of cardiovascular disease

Scientific Reports ◽

10.1038/s41598-020-80835-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hirotaka Saito ◽

Kenichi Tanaka ◽

Tsuyoshi Iwasaki ◽

Akira Oda ◽

Shuhei Watanabe ◽

...

Keyword(s):

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Xanthine Oxidase ◽

Cardiovascular Events ◽

Oxidase Inhibitor ◽

Cardiovascular Risks ◽

Diabetic Mellitus ◽

Xanthine Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitors ◽

Reduced Risk

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.

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Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger, on production of nitric oxide in RAW 264.7 macrophages

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/s0304-4165(99)00210-x ◽

2000 ◽

Vol 1474 (1) ◽

pp. 93-99 ◽

Cited By ~ 7

Author(s):

H Mori

Keyword(s):

Nitric Oxide ◽

Xanthine Oxidase ◽

Oxidase Inhibitor ◽

Raw 264.7 ◽

Xanthine Oxidase Inhibitor ◽

Raw 264.7 Macrophages ◽

Superoxide Scavenger

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The xanthine oxidase inhibitor oxypurinol does not limit infarct size in a canine model of 40 minutes of ischemia with reperfusion

Journal of the American College of Cardiology ◽

10.1016/0735-1097(88)90376-2 ◽

1988 ◽

Vol 12 (1) ◽

pp. 209-217 ◽

Cited By ~ 21

Author(s):

James M Kinsman ◽

Charles E Murry ◽

Vincent J Richard ◽

Robert B Jennings ◽

Keith A Reimer

Keyword(s):

Infarct Size ◽

Xanthine Oxidase ◽

Canine Model ◽

Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitor

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Fluorometric determination of uric acid in bovine milk

Journal of Dairy Research ◽

10.1017/s0022029910000580 ◽

2010 ◽

Vol 77 (4) ◽

pp. 438-444 ◽

Cited By ~ 17

Author(s):

Torben Larsen ◽

Kasey M Moyes

Keyword(s):

Heat Treatment ◽

Uric Acid ◽

Xanthine Oxidase ◽

Bovine Milk ◽

Oxidase Inhibitor ◽

Enzymatic Oxidation ◽

Fast Method ◽

Xanthine Oxidase Inhibitor ◽

Milk Samples

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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