Pterin-6-aldehyde, Xanthine Oxidase Inhibitor and Superoxide Scavenger, Directly React with Peroxynitrite

The effect of pterin-6-aldehyde (P6A), xanthine oxidase inhibitor and superoxide scavenger, on the production of nitrotyrosine as a footprint of tyrosine nitration by peroxynitrite, was compared with that of uric acid, a peroxynitrite scavenger. The amounts of tyrosine, P6A and nitrotyrosine were quantified using reversed-phase high-performance liquid chromato-graphy (RP-HPLC). P6A suppressed nitrotyrosine formation less effectively than uric acid, that is, 0.25 mM P6A reduced nitrotyrosine formation to 67.9± 10.8%, while 0.025 mM uric acid reduced it to 34.2± 1.6%. In living systems, peroxynitrite is generated by the reaction of super-oxide with nitric oxide and has a variety of toxic effects. Our results show that P6A is not necessarily a strong scavenger of peroxynitrite. However, since P6A is a potent scavenger of superoxide, P6A is thought to totally suppress peroxynitrite generation. Compounds that scavenge both superoxide and peroxynitrite may be useful in tissue damage in which reactive oxygen species are involved.

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Abstract 38: Reactive Oxygen Species Contribute To Aneurysmal Rupture in Mice

Stroke ◽

10.1161/str.44.suppl_1.a38 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Kenji Shimada ◽

Yoshiteru Tada ◽

Kosuke Wada ◽

Mari Kudo ◽

Shoko Murakami ◽

...

Keyword(s):

Nadph Oxidase ◽

Xanthine Oxidase ◽

Intracranial Aneurysms ◽

Oxidase Inhibitor ◽

Oxygen Species ◽

Gelatinase Activity ◽

Xanthine Oxidase Inhibitor ◽

Aneurysmal Rupture ◽

Nadph Oxidase Inhibitor ◽

Superoxide Scavenger

Background and Purpose: Inflammation and apoptosis are recognized as key factors for aneurysmal rupture. Reactive oxygen species (ROS) mediates both inflammation and apoptosis in vascular walls. Therefore, we hypothesized that ROS produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture. Recently we have demonstrated the feasibility of using a mouse model of intracranial aneurysms to test pharmacological therapies for the prevention of aneurysmal rupture. We tested the hypothesis by using this newly established mouse model. Methods: Intracranial aneurysms were induced in male mice using a combination of a single injection of elastase into the cerebrospinal fluid and the deoxycorticosterone acetate (DOCA) salt hypertension. Six days after aneurysm induction, we started 2-week treatment with vehicle (n=27), a superoxide scavenger (tempol; n=13), a xanthine oxidase inhibitor (oxypurinol; n=15), and a NADPH oxidase inhibitor (apocynin; n=16). Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage. Dihydroethidium staining and in situ zymography were performed to detect superoxide production and gelatinase activity, respectively. Results: A superoxide scavenger (tempol) significantly reduced rupture rate (vehicle vs. tempol: 74% vs. 27%, P < 0.05) (Figure1). It reduced superoxide production and gelatinase activity in aneurysmal walls (Figure2). Furthermore, the xanthine oxidase inhibitor (oxypurinol), and the NADPH oxidase inhibitor (apocynin) reduced the rupture rate (vehicle vs. oxypurinol: 74% vs. 30%, P< 0.05, vehicle vs. apocynin: 74% vs. 33%, P < 0.05). Conclusion: Our results indicate that superoxide produced by xanthine oxidase and NADPH oxidase contributes to aneurysmal rupture, by activating matrix metalloproteinases.

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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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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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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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