scholarly journals Allopurinol inhibits excess glucose-induced trophoblast IL-1β and ROS production

Reproduction ◽  
2020 ◽  
Vol 159 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Masaru Negi ◽  
Melissa J Mulla ◽  
Christina S Han ◽  
Vikki M Abrahams
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Ros Production ◽  
Human Trophoblast ◽  
Xanthine Oxidase Inhibitor ◽  
Adverse Pregnancy ◽  
Excess Glucose ◽  
Trophoblast Cell Line

Pre-gestational diabetes is a risk factor for preeclampsia, a condition associated with inflammatory markers, a dysregulated angiogenic profile, and impaired placentation. Using an in vitro model, we previously reported that hyperglycemic levels of glucose induced a pro-inflammatory (IL-1β, IL-8, RANTES, GRO-α), anti-angiogenic (sFlt-1) and anti-migratory profile in a human trophoblast cell line. The IL-1β response to excess glucose was mediated by uric acid-induced activation of the NLRP3 inflammasome. Allopurinol is a xanthine oxidase inhibitor that inhibits uric acid and reactive oxygen species (ROS) production. Thus, we sought to test the effects of allopurinol on the IL-1β and other inflammatory, angiogenic and migratory responses that are triggered in the trophoblast by excess glucose. Under excess glucose conditions, allopurinol significantly inhibited trophoblast secretion of inflammatory IL-1β; caspase-1 activity; IL-8; RANTES; and GRO-α. Allopurinol also significantly inhibited excess glucose-induced trophoblast secretion of anti-angiogenic sFlt-1. The presence of IL1Ra significantly inhibited excess glucose-induced trophoblast IL-8 and GRO-α secretion but had no effect on RANTES or sFlt-1. Conversely, DPI, a ROS inhibitor, significantly inhibited excess glucose-induced trophoblast GRO-α and sFlt-1 secretion, but had no effect on IL-8 or RANTES. Together, our findings indicate that the xanthine oxidase inhibitor allopurinol inhibited excess glucose-induced trophoblast IL-1β secretion. Additionally, through its inhibition of both IL-1β and ROS production by the trophoblast, allopurinol reduced the additional pro-inflammatory and anti-angiogenic responses to excess glucose. Thus, allopurinol may be a candidate medication to prevent placental dysfunction and adverse pregnancy outcomes, such as preeclampsia, in pregnant women with diabetes.

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

2020 ◽  
Vol 20 (2) ◽  
pp. 253-256 ◽  
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.

Fluorometric determination of uric acid in bovine milk

2010 ◽  
Vol 77 (4) ◽  
pp. 438-444 ◽  
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.

scholarly journals Absorption of Hemoglobin Iron: The Role of Xanthine Oxidase in the Intestinal Heme-Splitting Reaction

Blood ◽  
1970 ◽  
Vol 35 (1) ◽  
pp. 94-103 ◽  
Author(s):  
R. BEN DAWSON ◽  
SHEILA RAFAL ◽  
LEWIS R. WEINTRAUB
Keyword(s):  
Epithelial Cell ◽  
Xanthine Oxidase ◽  
Intestinal Epithelial Cell ◽  
Oxidase Inhibitor ◽  
Small Intestinal Mucosa ◽  
Intestinal Epithelial ◽  
Sephadex Column ◽  
Xanthine Oxidase Inhibitor

Abstract Heme from ingested hemoglobin—59Fe is taken into the epithelial cell of the small intestinal mucosa of the dog and the 59Fe subsequently appears in the plasma bound to transferrin. A substance was demonstrated in homogenates of the mucosa which releases iron from a hemoglobin substrate in vitro. Thus: (1) The addition of catalase to the mucosal homogenate reduces the "heme-splitting" reaction. In contrast, sodium azide, a catalase inhibitor, potentiates the reaction. This suggests that a peroxide generating system participates in the "heme-splitting" reaction. (2) Xanthine oxidase, an enzyme present in the intestinal epithelial cell, produces H2O2 by oxidation of its substrate. The addition of allopurinol, a xanthine oxidase inhibitor, to the intestinal mucosal homogenate diminishes the "heme-splitting" reaction. (3) Fractionation of the 50,000 Gm. supernatant of the mucosal homogenate on a G-200 Sephadex column shows the "heme-splitting" activity to have the same elution volume as xanthine oxidase, indicating a similar molecular weight. (4) The addition of a mucosal homogenate to a xanthine substrate results in the production of uric acid. These data suggest that xanthine oxidase in the intestinal epithelial cell is important in the release of iron from absorbed heme. The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.

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

Pteridines ◽  
1999 ◽  
Vol 10 (1) ◽  
pp. 32-34
Author(s):  
Hiroko Mori ◽  
Toshiyuki Arai ◽  
Hisanari Ishii ◽  
Nobuyuki Endo ◽  
Toshinori Suzuki ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
High Performance ◽  
Reversed Phase ◽  
Oxidase Inhibitor ◽  
Tyrosine Nitration ◽  
Oxygen Species ◽  
Xanthine Oxidase Inhibitor ◽  
Rp Hplc ◽  
Superoxide Scavenger

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.

Abstract 12506: Therapeutic Strategy for Efficient Reduction of Serum Uric Acid With Allopurinol versus Benzbromarone in Hyperuricemic Patients With Cardiovascular Disease ~ A Randomized Crossover Study (TERAO study) ~

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sunao Kojima ◽  
Shinobu Kojima ◽  
Hirofumi Soejima ◽  
Hisao Ogawa
Keyword(s):  
Cardiovascular Disease ◽  
Uric Acid ◽  
Crossover Study ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Cardiovascular Events ◽  
Oxidase Inhibitor ◽  
Creatinine Ratio ◽  
Cardiovascular Risks ◽  
Xanthine Oxidase Inhibitor

Introduction: Hyperuricemia is considered to be a marker of future cardiovascular events. Uricosuric agents and urate synthesis inhibitors has been widely used in hyperuricemic patients. Hypothesis: We assessed the hypothesis that the different mechanism of these drugs has an impact on urine albumin-creatinine ratio (ACR) associated with cardiovascular risks. Methods: A total of 14 hyperuricemic patients (serum uric acid levels >7 mg/dL) with cardiovascular disease were randomly assigned and treated with either benzbromarone, 25mg once daily, or allopurinol, 200 mg twice daily for 2 weeks, followed by a 2-week washout period, then a 2-week crossover phase. Results: Serum uric acid levels were comparable and similarly reduced with benzbromarone (8.4±1.1→4.8±1.3 mg/dL, P<0.0001) and allopurinol (8.4±1.0→5.1±0.9 mg/dL, P<0.0001). However, allopurinol significantly reduced urine ACR compared with benzbromarone (Figure 1). A logistic regression analysis revealed that influential clinical factors on reduced urine ACR were not observed except for allopurinol administration. The change of urine ACR was positively correlated with the change of urinary urate-creatinine ratio (UCR), indicating a substitution for xanthine oxidase activity (Figure 2). Conclusions: In this short-term, crossover study in hyperuricemic patients with cardiovascular disease, a treatment with xanthine oxidase inhibitor resulted in a reduction of urine ACR. These results represent a novel potential therapeutic approach with antioxidant strategy, which may lead to a reduction of future cardiovascular events. These preliminary findings require confirmation in larger clinical trials.

A Quantitative Study of Skeletal-Muscle Purines and Pyrazolo[3,4-d]Pyrimidines in Gout Patients Treated with Allopurinol

1971 ◽  
Vol 41 (2) ◽  
pp. 153-158 ◽  
Author(s):  
R. W. E. Watts ◽  
W. Snedden ◽  
R. A. Parker
Keyword(s):  
Skeletal Muscle ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Muscle Tissue ◽  
High Resolution Mass Spectrometry ◽  
Oxidase Inhibitor ◽  
Oxidase Deficiency ◽  
Xanthine Oxidase Inhibitor ◽  
Measurable Amount ◽  
Muscle Biopsies

1. Hypoxanthine, xanthine, uric acid, allopurinol and oxipurinol have been determined in skeletal-muscle biopsies by quantitative high-resolution mass spectrometry. 2. The results obtained in six untreated gout patients and in seven gout patients who had been treated with the xanthine oxidase inhibitor allopurinol for periods of about 2 years, have been compared with those obtained on muscle tissue from non-gouty subjects and with the results of previous microscopical studies of the same biopsies. 3. Measurable amounts of xanthine were detected more frequently in the allopurinol-treated gout patients than in the untreated patients. The concentration of uric acid was generally lower in the allopurinol-treated than in the untreated gout patients' muscle; and all except one of the allopurinol-treated subjects' tissue contained a measurable amount of oxipurinol. Allopurinol was detected less frequently than oxipurinol. 4. The concentrations of hypoxanthine and xanthine in the allopurinol-treated patients' muscle tissue are very much less than those which have been reported in congenital xanthine oxidase deficiency. 5. It is concluded that allopurinol can still be recommended as a useful drug in the treatment of gout but that longer studies during the clinical use of the drug would be of value.

Sign in / Sign up

Export Citation Format

Share Document