Sunflower head enzymatic hydrolysate relives hyperuricemia by inhibiting crucial proteins (xanthine oxidase, adenosine deaminase, uric acid transporter1) and restoring gut microbiota in mice

This study was designed to investigate the effects and underlying mechanisms of Astaxanthin (AST) on high-fructose-induced hyperuricemia (HUA) from the perspectives of the uric acid (UA) synthesis and excretion in rat models. Following six weeks of a 10% fructose diet, the level of serum UA effectively decreased in the AST groups as compared to the model group. The enzymatic activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly inhibited, and the mRNA expression levels of XOD and ADA significantly decreased after the AST administration. These results suggested that the AST reduced UA synthesis by inhibiting the mRNA expressions and enzyme activities of XOD and ADA, thereby contributing to HUA improvement. On the hand, the relative expressions of the mRNA and protein of kidney reabsorption transport proteins (GLUT9 and URAT1) were significantly down-regulated by AST, while that of the kidney secretion proteins (OAT1, OAT3 and ABCG2) were significantly up-regulated by AST. These results indicated that the AST promoted UA excretion by regulating the urate transport proteins, and thus alleviated HUA. This study suggested that the AST could serve as an effective alternative to traditional medicinal drugs for the prevention of fructose-induced HUA.

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Inhibition of dipeptidyl peptidase-4 averts Free Fatty acids deposition in the hearts of oral estrogen-progestin contraceptive-induced hyperinsulinemic female rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2021-0043 ◽

2021 ◽

Author(s):

Tolulope Eniola Omolekulo ◽

Isaiah Woru Sabinari ◽

Emmanuel Damilare Areola ◽

Folasade O Ajao ◽

Olayinka Olawale Asafa ◽

...

Keyword(s):

Lipid Peroxidation ◽

Fatty Acids ◽

Uric Acid ◽

Free Fatty Acids ◽

Xanthine Oxidase ◽

Adenosine Deaminase ◽

Plasma Insulin ◽

Dipeptidyl Peptidase ◽

Female Rats ◽

Dipeptidyl Peptidase 4

Free fatty acids deposition in non-adipose tissues such as the heart is a characteristic of insulin resistant states which features hyperinsulinemia and dipeptidyl peptidase-4 (DPP-4) activation. Estrogen-progestin oral contraceptives (OC) treatment reportedly increased DPP-4 activity in rat tissue and DPP-4 inhibitors have anti-diabetic and anti-inflammatory properties. This study aims to investigate the effects of DPP-4 inhibition on cardiac free fatty acid (FFA) deposition in estrogen-progestin treated female rats.From our data, estrogen-progestin OC exposure in female rats led to elevated plasma insulin, cardiac DPP-4 activity, FFA and triglyceride (TG) accumulation, Triglyceride/high density lipoprotein (TG/HDL) ratio, adenosine deaminase/xanthine oxidase/uric acid pathway, lipid peroxidation, glycogen synthase activity and alanine phosphatase whereas cardiac glucose-6-phosphate dehydrogenase, Na/K-ATPase and nitric oxide (NO) were decreased. However, DPP-4 inhibition resulted in decreased plasma insulin, cardiac DPP-4 activity, FFA, TG and TG/HDL-C ratio and alkaline phosphatase. These were accompanied by reduced adenosine deaminase/xanthine oxidase/uric acid (ADA/XO/UA) pathway, lipid peroxidation and augmented NO and Na/K-ATPase in estrogen-progestin OC-treated rats.DPP-4 inhibition attenuated cardiac lipid deposition accompanied by reduced activity in the ADA/XO/UA pathway in estrogen-progestin OC-treated female rats. DPP-4 is therefore a plausible therapeutic target in cardiometabolic disorders

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Chain-breaking/Preventive Antioxidant, Urate-lowering, and Anti-inflammatory Effects of Pure Curcumin

Current Nutrition & Food Science ◽

10.2174/1573401316999200421095134 ◽

2020 ◽

Vol 17 (1) ◽

pp. 66-74

Author(s):

Seghira Bisset ◽

Widad Sobhi ◽

Chawki Bensouici ◽

Abdelhalim Khenchouche

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Acid Production ◽

Biological Activities ◽

Antioxidant Effect ◽

Metal Chelating ◽

Wide Range ◽

Chain Breaking ◽

Pharmaceutical Industries ◽

Anti Inflammatory

Background: Several researches have shown that therapeutic compounds or phytochemicals from natural sources are important in the food as it is valuable in pharmaceutical industries due to their fewer side effects and potent against various diseases. Curcumin, a major polyphenol derived from turmeric spice, which used in many foods, has a wide range of biological activities, with quite a safety. Objective: The goal of this study was to investigate the antioxidant, urate-lowering, and antiinflammatory effects of pure curcumin. Methods: The antioxidant activity was evaluated for chain-breaking antioxidant effect (radicalscavenging and reducing abilities assays) and for preventive antioxidant effect with metal chelating assay, the urate-lowering was assayed on aspectrophotometer by measuring the inhibition of uric acid production by xanthine oxidase (XO) enzyme, and the anti-inflammatory effect was estimated using in vitro albumin denaturation inhibition. Results: Curcumin showed a significant and good chain-breaking antioxidant effect, both in free radical- scavenging assays (Galvinoxyl radical, ABTS, and hydroxyl radical), and in reducing abilities methods (reducing power, Cupric ion reducing antioxidant capacity and O-phenanthroline assays). In preventive antioxidant effect, assessed with the metal chelating assay, curcumin showed significant effect but with high concentration compared with standard. In the xanthine/xanthine oxidase system, curcumin significantly inhibited uric acid production (IC50=0.71 ± 0.06 mg/mL). Regarding antiinflammatory activity, curcumin showed significant inhibition of albumin denaturation with an IC50 value of 1181.69 ± 1.11μg/mL. Conclusion: These results indicated that curcumin showed promising antioxidant, anti-gout and antiinflammatory properties and might be used as potential, natural drugs against oxidative and inflammation- related diseases.

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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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Uric Acid, Oxidative Stress and Inflammation in Chronic Heart Failure with Reduced Ejection Fraction

Revista Romana de Medicina de Laborator ◽

10.1515/rrlm-2015-0039 ◽

2015 ◽

Vol 23 (4) ◽

pp. 397-406 ◽

Cited By ~ 3

Author(s):

Adriana Iliesiu ◽

Alexandru Campeanu ◽

Daciana Marta ◽

Irina Parvu ◽

Gabriela Gheorghe

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Uric Acid ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Xanthine Oxidase ◽

Left Ventricular ◽

Paraoxonase 1 ◽

Lv Function ◽

The Relationship

Abstract Background. Oxidative stress (OS) and inflammation are major mechanisms involved in the progression of chronic heart failure (CHF). Serum uric acid (sUA) is related to CHF severity and could represent a marker of xanthine-oxidase activation. The relationship between sUA, oxidative stress (OS) and inflammation markers was assessed in patients with moderate-severe CHF and reduced left ventricular (LV) ejection fraction (EF). Methods. In 57 patients with stable CHF, functional NYHA class III, with EF<40%, the LV function was assessed by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels and echocardiographically through the EF and E/e’ ratio, a marker of LV filling pressures. The relationship between LV function, sUA, malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase 1 (PON-1) as OS markers and high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) as markers of systemic inflammation was evaluated. Results. The mean sUA level was 7.9 ± 2.2 mg/dl, and 61% of the CHF patients had hyperuricemia. CHF patients with elevated LV filling pressures (E/e’ ≥ 13) had higher sUA (8.6 ± 2.3 vs. 7.3 ± 1.4, p=0.08) and NT-proBNP levels (643±430 vs. 2531±709, p=0.003) and lower EF (29.8 ± 3.9 % vs. 36.3 ± 4.4 %, p=0.001). There was a significant correlation between sUA and IL-6 (r = 0.56, p<0.001), MDA (r= 0.49, p= 0.001), MPO (r=0.34, p=0.001) and PON-1 levels (r= −0.39, p= 0.003). Conclusion. In CHF, hyperuricemia is associated with disease severity. High sUA levels in CHF with normal renal function may reflect increased xanthine-oxidase activity linked with chronic inflammatory response.

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High-Fructose Diet Increases Inflammatory Cytokines and Alters Gut Microbiota Composition in Rats

Mediators of Inflammation ◽

10.1155/2020/6672636 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yong Wang ◽

Wentao Qi ◽

Ge Song ◽

Shaojie Pang ◽

Zhenzhen Peng ◽

...

Keyword(s):

Uric Acid ◽

Inflammatory Response ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Proinflammatory Cytokines ◽

Lipid Accumulation ◽

Fasting Blood Glucose ◽

High Fructose Diet ◽

Fructose Intake ◽

High Fructose

High-fructose diet induced changes in gut microbiota structure and function, which have been linked to inflammatory response. However, the effect of small or appropriate doses of fructose on gut microbiota and inflammatory cytokines is not fully understood. Hence, the abundance changes of gut microbiota in fructose-treated Sprague-Dawley rats were analyzed by 16S rRNA sequencing. The effects of fructose diet on metabolic disorders were evaluated by blood biochemical parameter test, histological analysis, short-chain fatty acid (SCFA) analysis, ELISA analysis, and Western blot. Rats were intragastrically administered with pure fructose at the dose of 0 (Con), 2.6 (Fru-L), 5.3 (Fru-M), and 10.5 g/kg/day (Fru-H) for 20 weeks. The results showed that there were 36.5% increase of uric acid level in the Fru-H group when compared with the Con group. The serum proinflammatory cytokines (IL-6, TNF-α, and MIP-2) were significantly increased ( P < 0.05 ), and the anti-inflammatory cytokine IL-10 was significantly decreased ( P < 0.05 ) with fructose treatment. A higher fructose intake induced lipid accumulation in the liver and inflammatory cell infiltration in the pancreas and colon and increased the abundances of Lachnospira, Parasutterella, Marvinbryantia, and Blantia in colonic contents. Fructose intake increased the expressions of lipid accumulation proteins including perilipin-1, ADRP, and Tip-47 in the colon. Moreover, the higher level intake of fructose impaired intestinal barrier function due to the decrease of the expression of tight junction proteins (ZO-1 and occludin). In summary, there were no negative effects on body weight, fasting blood glucose, gut microbiota, and SCFAs in colonic contents of rats when fructose intake is in small or appropriate doses. High intake of fructose can increase uric acid, proinflammatory cytokines, intestinal permeability, and lipid accumulation in the liver and induce inflammatory response in the pancreas and colon.

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Could uric acid reduction by specific xanthine oxidase inhibition improve vascular function and reduce cardiovascular risk?

Journal of Clinical Hypertension ◽

10.1111/jch.13693 ◽

2019 ◽

Vol 21 (11) ◽

pp. 1721-1723

Author(s):

Jamario Skeete ◽

Emily Ridley ◽

Donald J. DiPette

Keyword(s):

Uric Acid ◽

Cardiovascular Risk ◽

Xanthine Oxidase ◽

Vascular Function ◽

Oxidase Inhibition ◽

Xanthine Oxidase Inhibition ◽

Acid Reduction

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Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte.

Journal of Experimental Medicine ◽

10.1084/jem.149.1.27 ◽

1979 ◽

Vol 149 (1) ◽

pp. 27-39 ◽

Cited By ~ 133

Author(s):

H Rosen ◽

S J Klebanoff

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Bactericidal Activity ◽

Parent Strain ◽

Carotenoid Pigments ◽

Bacterial Killing ◽

Oxidase System ◽

System A ◽

Presence And Absence ◽

Generating System

The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.

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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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