Serum Xanthine Oxidase Research Articles

Evaluation of the relationship between xanthine oxidase activity and metabolic syndrome in a population group in Bangladesh

Xanthine oxidase (XO) is an enzyme that converts hypoxanthine into xanthine and xanthine into uric acid, which is then eliminated by the kidneys. Serum XO has been linked to diabetes, hypertension, liver dysfunction, and cardiovascular diseases. However, limited information exists on the relationship between serum XO activity and MetS. This study aimed to analyze the relationship between XO activity and metabolic syndrome (MetS) and its components in an adult population group in Bangladesh A total of 601 participants aged ≥18 years were included in the study. MetS was defined based on the criteria set by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Serum XO activity was measured using the enzyme-linked immunosorbent assay (ELISA), while other biochemical parameters were measured using colorimetric methods. The relationship between serum XO and MetS levels was determined through multivariate logistic regression analysis. Serum XO activity was found to be significantly higher in females (6.17 ± 3.77 U/L) as compared to males (4.00 ± 2.77 U/L) (p < 0.001). Furthermore, participants with MetS had significantly higher mean levels of serum XO (5.34 ± 3.39 U/L) than those without MetS (3.86 ± 2.90 U/L) (p < 0.001). The prevalence of MetS and its components, such as blood pressure and blood glucose increased across the XO quartiles (p < 0.001). Regression analysis indicated that XO activity was significantly and independently associated with the prevalence of MetS (at least p < 0.05 for all cases) and its components, including elevated blood pressure, high blood glucose, and low HDL-C (at least p < 0.05 for all cases). In conclusion, individuals with MetS had significantly higher XO levels than those without MetS. Serum XO activity showed an independent association with MetS and some of its components. Therefore, XO might serve as a useful marker of MetS. Prospective studies are needed to determine the underlying mechanisms linking XO and MetS.

Ilex cornuta leaves extracts ameliorate hyperuricemia by modulating uric acid transporters

Ethnopharmacological relevanceIlex cornuta is a valuable species of the Holly genus (Aquifoliaceae), and mainly distributed in eastern China. It is not only made into tea, namely Kudingcha, but also used as traditional medicine to relieve cough, headache, gout, and nourish liver and kidney. Aim of the studyThe purpose of this study was to explore the exact efficacy of different extracts from Ilex cornuta in the treatment of hyperuricemia in vitro and in vivo, and to explore its pharmacological mechanism, so as to bring new ideas for the development of new drugs for reducing uric acid (UA) and anti-gout. Materials and methodsFive crude extracts from Ilex cornuta leaves were extracted by different methods. Then, the xanthine oxidase inhibitory activity and antioxidant capacity of 5 extracts in vitro were compared to screen the extract with the most UA regulating potential. In vivo experiment, hyperuricemia model of mice was established by intragastric administration of potassium oxonate and feeding high yeast diet. Biochemical indexes such as serum UA level, xanthine oxidase activity, liver and kidney index of mice in each group were detected. The pathological sections of kidney and liver tissues were also observed and compared. The mechanism of Ilex cornuta leaves (western blotting, and RT-qPCR) in the treatment of hyperuricemia was further explored by targeting UA transporters ABCG2, GLUT9, and URAT1. ResultsThe in vitro results of inhibitory activity of xanthine oxidase showed that the crude saponin extract was the best, followed by crude flavonoids extract. Then, the in vivo results reflected that both crude saponins and crude flavonoids extracts could significantly reduce the serum UA level, inhibit the activity of xanthine oxidase in serum and liver, and maintain serum urea nitrogen and creatinine at normal level. Meanwhile, there was no liver and kidney injury in mice. Through the comparison of the mechanism results, it was found that both extracts could up-regulate the expression of ABCG2 protein and mRNA related to UA excretion, and down-regulate the expression of GLUT9 and URAT1 protein and mRNA. ConclusionThe crude flavonoids and saponins of Ilex cornuta leaves not only inhibited XOD activity in vitro, but also significantly controlled XOD activity and reduced UA level in hyperuricemia mice in vivo. One of the potential mechanisms was to regulate UA level in vivo by regulating ABCG2, GLUT9, and URAT1 transporters directly related to UA transport, thus achieving the effect of intervening hyperuricemia. This study provided a preliminary experimental basis for the development of new drugs of Ilex cornuta leaves for treating hyperuricemia.

Ameliorative action of "daitongxiao" against hyperuricemia includes the "uric acid transporter group".

This study aimed to investigate the potential mechanisms involved in the therapeutic effects of daitongxiao (DTX) on hyperuricemia (HUA). DTX was administered to two animal models of HUA via gavage feeding: HUA quail model (a uricotelic animal with urate oxidase deficiency), treated continuously for 35 days post-HUA induction, and HUA rats (an animal with active urate oxidase), treated continuously for 28days post-HUA induction. HUA was induced in quail by administering a solution of sterile dry yeast powder via gavage feeding, while in rats, it was induced by intragastric gavage feeding of a solution of adenine and ethambutol hydrochloride. DTX improved overall health; increased bodyweight; reduced renal index, serum urate levels, serum xanthine oxidase activity, blood urea nitrogen, and creatinine; and enhanced urinary and fecal uric acid (UA) excretion in these two animal models. The results of hematoxylin and eosin and hexamine silver staining of kidney sections revealed that DTX significantly mitigated HUA-induced renal structural damage and inflammatory response. The results of quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence analyses revealed that DTX downregulated the renal expression levels of glucose transporter 9 (GLUT9) and upregulated the renal expression levels of organic anion transporters (OAT1 and OAT3) in both HUA models. Thus, the findings of this study suggest that DTX suppresses the progression of HUA by modulating the expression of the UA transporter group members.

Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota

Ethnopharmacological relevanceIn ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. Aim of the studyTo determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. Materials and methodsPotassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1β) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. ResultsIn this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1β. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. ConclusionRGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.

A potential therapeutic agent for the treatment of hyperuricemia and gout: 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide

Uric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and gout. Currently, treatment options remain limited for gout patients. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a derivative of the natural product protocatechualdehyde with good biological activity. In this work, we identify a DHNB thiosemicarbazide class of compounds that targets XOD. 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazone can effectively inhibit XOD activity (IC50 value: 0.0437 μM) and exhibits a mixed inhibitory effect. In a mouse model of acute hyperuricemia, a moderate dose (10 mg/kg.w) of 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide effectively controlled the serum uric acid content and significantly inhibited serum XOD activity. In addition, 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide showed favorable safety profiles, and mice treated with the target compound did not show any symptoms of general toxicity following a single dose of 500 mg/kg. In the allopurinol group, 50 % of the mice died. These results provide a structural framework and mechanism of XOD inhibition that may facilitate the design of hyperuricemia and gout treatments.

Elevated Serum Xanthine Oxidase and Its Correlation with Antioxidant Status in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at the late stage of the disease, where most dopaminergic neurons are already damaged. Several studies reported that oxidative stress is a key modulator in the development of PD. This condition occurs due to excess reactive oxygen species (ROS) production in the cellular system and the incapability of antioxidants to neutralize it. In this study, we focused on the pathology of PD by measuring serum xanthine oxidase (XO) activity, which is an enzyme that generates ROS. Interestingly, the serum XO activity of patients with PD was markedly upregulated compared to patients with other neurological diseases (ONDs) as a control. Moreover, serum XO activity in patients with PD showed a significant correlation with the disease severity based on the Hoehn and Yahr (HY) stages. The investigation of antioxidant status also revealed that serum uric acid levels were significantly lower in the severe group (HY ≥ 3) than in the ONDs group. Together, these results suggest that XO activity may contribute to the development of PD and might potentially be a biomarker for determining disease severity in patients with PD.

РАСПРЕДЕЛЕНИЕ ГЕНОТИПОВ ГЕНА SLC2A9, УРОВЕНЬ МОЧЕВОЙ КИСЛОТЫ И МЕТАБОЛИТЫ ПУРИНОВОГО ОБМЕНА У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ И ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ

The aim is to investigate the frequency of genotypes and alleles of the SLC2A9 gene rs734553 polymorphism, the level of serum uric acid (sUA) and metabolites of purine metabolism in patients with arterial hypertension (AH) and atrial fibrillation (AF), as well as in healthy individuals. Material and methods. The study included 154 patients: 50 were healthy individuals (group 0), of which 22 (44%) were men and 28 (56%) were women aged 50 [45;53] years and 104 were patients with AH and AF (main group), of which 94 (90.4%) were men and 10 (9.6%) were women aged 55 [45; 61] years. The main group was divided into subgroups: subgroup I – patients with AF without a history of AH and other rhythm disorders (n=13); subgroup II – patients with AH in combination with AF (n=68); subgroup III – patients with AH without a history of AF or other rhythm disturbances (n=23). Hyperuricemia was detected in 34 (22.1%) patients, normal uric acid levels were revealed in 120 (77.9%) patients. All patients were studied using clinical, laboratory, instrumental and molecular genetic research methods. The level of sUA was determined by the enzymatic colorimetric method. Serum xanthine oxidase was measured using a method based on a solid phase sandwich-type enzyme-linked immunosorbent assay. Metabolites of purine metabolism in blood plasma were measured using the method of high-performance liquid chromatography. The SLC2A9 gene rs734553 polymorphism was determined using the polymerase chain reaction with real-time detection of results. Results. The patients with AH and AF, as compared to healthy individuals, had more severe disturbances of purine metabolism, characterized by higher concentration of sUA (330 [283; 412] µmol/l and 197 [161; 229] µmol/l (p&lt;0.001), respectively). Also, in contrast to the group of healthy individuals, the group of patients with AH and AF demonstrated an increase in the level of adenosine (p=0.001), and a decrease in the levels of hypoxanthine and xanthine (p&lt;0.001). There were no statistically significant differences in xanthine oxidase activity level (p&gt;0.05), however, in 54% of patients in the main group it was higher than normal values. The dominant allele A and the dominant genotype A/A of the SLC2A9 gene rs734553 polymorphism (75%, p=0.005; 64%, p=0.001, respectively) occurred significantly more often in healthy individuals, while the recessive allele C and the heterozygous genotype A/C were found significantly more often in the group of patients with AH and AF (41.3%, p=0.005; 48.1%, p=0.003, respectively). The C/C genotype (41.7%, p=0.001) was significantly more common in patients with AH in combination with AF and hyperuricemia, compared to patients with AH combined with AF without hyperuricemia as well as healthy individuals (6.8%; 14%, p=0.001, respectively). Patients with AH in combination with AF and the C/C genotype were characterized by a significantly higher level of sUA (p=0.003) compared to patients with the A/A genotype. Conclusions. A statistically significant predominance of the recessive allele C of the SLC2A9 gene rs734553 polymorphism was established in patients with AH and AF compared with healthy individuals (p=0.005). In patients with AH in combination with AF and hyperuricemia, the C/C genotype was significantly more common (41.7%, p=0.001). Patients with AH in combination with AF and the C/C genotype were characterized by a significantly higher level of sUA (p=0.003) compared to patients with the A/A genotype.

Machine Learning–Based Clinical Prediction Models for Acute Ischemic Stroke Based on Serum Xanthine Oxidase Levels

Background and objectiveEarly prediction of the onset, progression and prognosis of acute ischemic stroke (AIS) is helpful for treatment decision-making and proactive management. Although several biomarkers have been found to predict the progression and prognosis of AIS, these biomarkers have not been widely used in routine clinical practice. Xanthine oxidase (XO) is a form of xanthine oxidoreductase (XOR), which is widespread in various organs of the human body and plays an important role in redox reactions and ischemia‒reperfusion injury. Our previous studies have shown that serum XO levels on admission have certain clinical predictive value for AIS. The purpose of this study was to utilize serum XO levels and clinical data to establish machine learning models for predicting the onset, progression and prognosis of AIS. Materials and MethodsWe enrolled 328 consecutive patients with AIS and 107 healthy controls from October 2020 to September 2021. Serum XO levels and stroke-related clinical data were collected. We established five machine learning models—the logistic regression (LR), support vector machine (SVM), decision tree, random forest, and K-nearest neighbor (KNN) models—to predict the onset, progression and prognosis of AIS. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, negative predictive value and positive predictive value were used to evaluate the predictive performance of each model. ResultsAmong the five machine learning models predicting AIS onset, the AUROC values of four prediction models were over 0.7, while that of the KNN model was lower (AUROC=0.6708, 95% CI 0.576-0.765). The LR model showed the best AUROC value (AUROC=0.9586, 95% CI 0.927-0.991). Although the five machine learning models showed relatively poor predictive value for the progression of AIS (all AUROCs < 0.7), the LR model still showed the highest AUROC value (AUROC=0.6543, 95% CI 0.453-0.856). We compared the value of five machine learning models in predicting the prognosis of AIS, and the LR model showed the best predictive value (AUROC=0.8124, 95% CI 0.715-0.910). ConclusionThe tested machine learning models based on serum levels of XO could predict the onset and prognosis of AIS. Among the five machine learning models, we found that the LR model showed the best predictive performance. Machine learning algorithms improve accuracy in the early diagnosis of AIS and can be used to make treatment decisions.

Fetoplacental unit involvement in uric acid production in women with severe preeclampsia: a prospective case control pilot study

Purpose Preeclampsia (PE) is a common complication of pregnancy that carries significant risks for both the mother and the fetus, and is frequently accompanied by hyperuricemia, yet the exact source of elevated uric acid (UA) levels remains partially elucidated. Several potential origins for increased UA levels include abnormal renal function, increased tissue breakdown, and increased activity of the enzyme Xanthine Oxidase (XO). The aim of the study was to determine serum levels of UA and XO not only in maternal serum, but also in umbilical vein (UV) and umbilical artery (UA) and explore their possible role in PE development. Methods A prospective case-control pilot study was conducted in women who were found positive for PE with severe features, and had elevated UA levels above 6 mg/dL, with normotensive pregnant women serving as controls. Renal function, UA and XO levels were measured in maternal, UV and UA serums immediately after delivery. They were then compared between PE (n = 21) and control (n = 18) groups, as well as across all mediums (maternal, UV and UA) among the total study sample (N = 39). Diastolic blood pressure (DBP) was also measured immediately following delivery. Results The mean serum maternal creatinine levels did not differ significantly between groups (0.65 ± 0.03 vs 0.6 ± 0.07, p = 0.13). Both mean maternal serum UA and XO concentrations were higher in PE group than in control (7.3 ± 1.2 vs 4.2 ± 0.9, p < 0.01 and 3.6 ± 3.5 Vs 1.7 ± 0.8, p < 0.01, respectively). The mean UV and UA serum XO concentrations were significantly higher in PE group compared to control (4.2 ± 3.6 vs 2.2 ± 1.4, p < 0.01 and 4.2 ± 3.6 vs 2.1 ± 1.5, p < 0.01, respectively). Polynomial fit correlation test demonstrated a significant association between maternal DBP and UV XO concentration for all the total study participants (p = 0.03). Conclusion Despite preserved renal functions, UA and XO levels were elevated in women with PE. Importantly, this pattern was found to be applied to the feto-placental unit as well, which may indicate an active involvement of the fetus in the hypoxic process. Further study is needed to clarify the possible role of the feto-placental unit in pregnancies complicated by PE.

Amantadine's Neuroprotective Effects in Rabbit Spinal Cord Ischemia/Reperfusion Model.

To examine the effects of amantadine, a drug with neuroprotective and anti-inflammatory activities on oxidative stress, tissue necrosis, apoptosis, and neurological recovery in an experimental rabbit spinal cord ischemia-reperfusion injury (SCIRI) model. A total of 32 rabbits were randomized into five groups: control, ischemia, vehicle, methylprednisolone (MP), and amantadine (AMT) (n=8/each). At 24th-hour neurological examination was performed, spinal cord tissues were collected, and biochemical and histopathological examinations were performed. When ischemia and vehicle groups were compared with control group, significant increase was seen in serum and tissue caspase-3, malondialdehyde (MDA), and myeloperoxidase (MPO) levels (p < 0.001); significant decrease was seen in serum and tissue catalase (CAT) levels (p < 0.001); and significant increase was seen in serum xanthine oxidase (XO) levels (p < 0.001). When the ischemia group and the MP and AMT groups were compared, low serum and tissue caspase-3 levels (p < 0.001), high serum and tissue CAT levels (p < 0.001), significantly low serum XO levels (p < 0.001), low serum and tissue MDA levels (p < 0.05) and tissue MPO levels (p < 0.001) were found. Both AMT and MP groups showed decreased histopathological score and higher number of normal neurons (p < 0.001) compared to ischemia group. Both AMT and MP showed better modified Tarlov scores compared to the ischemia group (p < 0.001). Our study found that AMT had antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective effects on SCIRI. We used biochemical, microscopic, and ultrastructural approaches to demonstrate these effects. AMT might be a candidate medication for SCIRI prophylaxis and treatment.

Temporal change of serum xanthine oxidase levels and its relation to clinical outcome of severe traumatic brain injury: a prospective cohort study.

Xanthine oxidase (XO) may be involved in the induction of oxidative stress and inflammation. We measured serum XO levels at multiple days to determine whether it is associated with the severity and prognosis of severe traumatic brain injury (sTBI). In this prospective cohort study, we quantified serum XO levels in 112 sTBI patients and 112 controls. Serum XO levels of patients were measured at admission and at days 1, 3, 5, 7, and 10 after sTBI. Extended Glasgow outcome scale scores of 1-4 at post-trauma 180 days were defined as a poor prognosis. Multivariate analysis was employed to determine the relationship between poor prognosis and serum XO levels at multiple days. Serum XO levels were significantly increased at admission among patients, afterwards elevated gradually, peaked at day 3, and then diminished gradually until day 10, and were substantially higher during 10 days in patients than in controls. Serum XO levels at 6 different days were all correlated with admission Rotterdam computed tomography (CT) scores and Glasgow coma scale (GCS) scores. Serum XO levels at 6 different days were all substantially higher in patients with poor prognosis than in those with good prognosis. Serum XO levels at days 7 and 10, but not at days 1, 3, and 5, had significantly lower area under receiver operating characteristic (AUC) than those at admission. Serum XO levels at admission and at days 1 and 3, but not at day 5, were independently associated with 180-day poor prognosis. Prognostic prediction model containing GCS scores, Rotterdam CT scores, and serum XO levels at admission (or at days 1 and 3) showed substantially higher AUC than GCS scores and Rotterdam CT scores alone. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Elevated serum XO levels during early period of sTBI are more closely associated with trauma severity and clinical adverse outcomes, assuming that serum XO may serve as a potential prognostic biomarker in sTBI.

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers.

Oral inosine loading is a new method to evaluate the effects of purine on urate metabolism. However, individuals respond differently to acute purine intake, and the effects on the metabolism of other purines remain to be explored. 35 male participants are recruited. Participants received 500mg of inosine orally after an overnight fast, and blood and urine samples are collected before and at various time points over 180min after inosine administration. The serum urate concentration is significantly different between the hyperuricemia (n = 14) and non-hyperuricemia (n = 16) groups before inosine intake, but there is no in urate change after inosine intake. When grouped according to the baseline estimated glomerular filtration rate (eGFR), the increase in urate level in the high-eGFR group is significantly higher than that in the low-eGFR group (p = 0.047). The high-eGFR group showed higher levels of serum xanthine and xanthine oxidase (XOD), the key enzyme in urate synthesis, after inosine loading (p < 0.01). The increase in urate level is positively related to eGFR after oral acute inosine administration, which may have been due to a higher level of XOD.

Effects of evodiamine on ROS/TXNIP/NLRP3 pathway against gouty arthritis.

Evodiamine (EVO) was tested on acute gouty arthritis rats to investigate its anti-inflammatory effect. Seventy-two male Sprague-Dawley (SD) rats were randomly assigned into the control, model, high, medium, and low dose of EVO groups and colchicine group. The ankle swelling degrees were measured at 2h, 6h, and 24h following sodium urate injection into ankle joint. Histopathological examination was performed 24h after injection. Reactive oxygen species (ROS) content in the ankle joint was detected using chemical fluorescence. Serum interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) content were determined by ELISA. Serum xanthine oxidase (XOD), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by spectrophotometry. The expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), pro-caspase-1, caspase-1, and apoptosis-related spot like protein (ASC) in synovium were detected by Western blot. Evodiamine alleviated the ankle swelling of the affected foot in gouty arthritis rats and reduced inflammatory cell infiltration in joint synovial tissue. Evodiamine also decreased the content of serum inflammatory factors including IL-1β, IL-18, and TNF-α, and increased serum SOD activity, while it decreased serum XOD, MDA activity, and ROS level. Moreover, evodiamine downregulated the protein expression levels of TXNIP, NLRP3, pro-caspase-1, cleavedcaspae-1, and ASC. The mechanism of EVO in treating gouty arthritis is associated with the inhibition of NLRP3 inflammasome by regulating the ROS/TXNIP/NLRP3 signaling pathway.

In vitro xanthine oxidase inhibitory and in vivo anti-hyperuricemic properties of sodium kaempferol-3'-sulfonate.

Xanthine oxidase (XO), a key enzyme in purine catabolism, catalyzes the oxidation of xanthine to uric acid in the body, but overproduction of uric acid may lead to hyperuricemia. This study aims to investigate in vitro XO inhibitory and in vivo anti-hyperuricemic properties of sodium kaempferol-3'-sulfonate (KS). The kinetic analysis indicates that KS is a reversible competitive inhibitor and has significant inhibitory effects on XO activity with an IC50 value of 0.338μM. Fluorescence spectra suggested that KS could cause fluorescence quenching and conformational changes of XO due to the formation of a KS-XO complex. Molecular docking studies demonstrated that KS interacted with several amino acid residues of XO by the π-π stacking, hydrogen bonds, and hydrophobic interactions. The inhibitory mechanism of KS on XO activity might be the insertion of KS into the active site of XO to prevent the entrance of the substrate xanthine and induce conformational changes of XO. The results carried out in hyperuricemic mice showed that KS reduced serum XO activity, serum uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) levels, as well as alleviating renal histopathological injury. These findings suggest that KS may be a new potent XO inhibitor against hyperuricemia-related diseases.

Guluronate oligosaccharides exerts beneficial effects on hyperuricemia and regulation of gut microbiota in mice

Guluronate oligosaccharides (GOS) is a biologically active natural product derived from brown algae. This study aimed to evaluate the amelioration of hyperuricemia and renal inflammation by GOS and its mechanisms. According to the results, GOS treatment reduced the serum uric acid (UA) and blood urea nitrogen (BUN) levels among hyperuricemic mice by 19.6% and 21.5% (P<0.05), at the same time, serum xanthine oxidase (XOD) and adenosine deaminase (ADA) levels were down-regulated to normal. GOS treatment ameliorated the renal pathologization associated with hyperuricemia and reduced renal IL-1β, IL-12, and IL-18 (P<0.05), suggesting a mitigating effect of GOS on renal damage. In addition, GOS supplementation modulates the mRNA levels of renal and intestinal urate transporters to promote uric acid excretion. GOS reversed the intestinal microbiota of hyperuricemic mice, significantly down-regulating the abundances of pernicious bacteria like Bilophila and Tuzzerella, while up-regulating the beneficial intestinal bacteria including Muribaculum, Lachnospiraceae_UCG_006, Ruminococcus, Faecalibaculum, and Lachnospiraceae_NK4A136_group. Together, guluronate oligosaccharides can improve hyperuricemia by alleviating hyperuricemia-induced renal damage and reversing intestinal microbiota disorders. These findings provide evidence supporting the further development of guluronate oligosaccharides as a novel functional food ingredient suitable for hyperuricemia.

Increased activity of enzymes involved in purine metabolism as one of the factors of rectal cancer pathogenesis

Aim: to study changes in the activities of purine nucleotide degradation enzymes – adenosine deaminase (ADA) and xanthine oxidase (XO) in patients with rectum cancer (RC).Material and Methods. The activity of purine nucleotide degradation enzymes was studied in blood plasma and tissue homogenates: tumor tissue and normal rectal mucosa in 70 patients with stage I–IV RC. The histological type of RC was adenocarcinoma. The levels of ADA and XO activities were measured using spectrophotometry.Results. The activity of ADA and XO in blood serum of RC patients was significantly higher than that of healthy people. A significant increase in the activity of ADA and XO in tumor tissue compared to normal tissue was also found. The relationship between the activities of the enzymes of purine catabolism in blood plasma and tissues were revealed. An increase in purine catabolism depending on the stage of RC was found.Conclusion. The increased ADA and XO activities indicated the enhanced purine catabolism not only in malignant transformation, but also in tumor progression.

The clinical value of serum xanthine oxidase levels in patients with acute ischemic stroke

Xanthine oxidase (XO), a form of xanthine oxidoreductase, is widely distributed in various human tissues. As a major source for the generation of superoxide radicals, XO is involved in the induction of oxidative stress and inflammation during ischemic and hypoxic tissue injury. Therefore, we designed this study to identify the role of serum XO levels in acute ischemic stroke (AIS) pathogenesis. In this single-center prospective study, 328 consecutive patients with AIS for the first time were included, and 107 age- and sex-matched healthy controls from a community-based stroke screening population were also included. The serum levels of XO and several conventional stroke risk factors were assessed. Multivariate analysis was applied to evaluate the relationship between serum levels of XO and clinical outcomes, and nomogram models were developed to predict the onset, progression and prognosis of AIS. Compared with the healthy control group, the serum level of XO was significantly higher in the AIS group (P < 0.05) and was an independent risk factor for AIS (OR 8.68, 95% CI 4.62–14.33, P < 0.05). Patients with progressive stroke or a poor prognosis had a much higher serum level of XO than patients with stable stroke or a good prognosis (all P < 0.05). In addition, the serum level of XO was an independent risk factor for stroke progression (OR 1.98, 95% CI 1.12–3.50, P = 0.018) and a poor prognosis (OR 2.51, 95% CI 1.47–3.31, P = 0.001). The nomogram models including XO to predict the onset, progression and prognosis of AIS had good prediction and differentiation abilities. The findings of this study show that the serum level of XO on admission was an independent risk factor for AIS and had certain clinical predictive value for stroke progression and prognosis in patients with AIS.

Impact of Activity of Xanthine Oxidase on Some Biomarkers in Patients with Kidney Stones in Iraqi Patients

Objective: Kidney stones are crystalline concrete that often develops inside the kidneys. Urinary tract problems are getting worse and worse for human health. The risk of end-stage kidney failure has been associated with increase the level of a new biomarker (like xanthine oxidase) to assess severity of kidney injury. Methods: The eighty patients, who attended the government clinics in Yarmouk Teaching Hospital, and the forty healthy people were used as a control group. Colorimetric assays were used to assess serum xanthine oxidase (XO) and other biochemical parameters. Using an enzyme-linked immunosorbent assay was determined. Results: The mean serum XO activity (8.8525 IU/L) was significantly greater than the corresponding values for the controls (6.5825 IU/L). Patients with kidney stones showed abnormal activity of uric acid levels in 78.33% of cases, while XO activity showed highly sensitive (70%) and high specificity (79%). XO has been found to be an excellent biomarker for detecting damage of the kidney in people suffering from kidney stones.

Association of serum xanthine oxidase levels with hypertension: a study on Bangladeshi adults

Xanthine oxidase (XO) is a metalloflavoenzyme associated with the uric acid formation in purine metabolism. Serum XO has been suggested to be associated with liver and kidney dysfunction, diabetes and cardiovascular diseases. However, there is limited information on the relationship between serum XO levels and hypertension. This study aimed to assess the relationship between serum XO levels and hypertension in Bangladeshi adults. In this study, fasting blood samples were collected from 312 participants (225 males and 87 females), aged ≥ 20 years. Serum levels of XO were determined by ELISA and other biochemical parameters including serum uric acid (SUA) were measured by colorimetric methods. Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or self-reported recent use of anti-hypertensive medications. Association between serum XO levels and hypertension was evaluated by multinomial logistic regression analysis. The mean level of XO was significantly higher (p < 0.001) in females (5.8 ± 3.2 U/L) than in males (3.9 ± 2.5 U/L). When the participants were divided by blood pressure levels, the mean level of serum XO was significantly higher (p < 0.01) in the hypertensive group (5.0 ± 2.7 U/L) compared to the normotensive control group (4.0 ± 2.7 U/L). An increasing trend for SBP and DBP levels was observed across the XO quartiles (at least p < 0.01 for both cases). A significant positive correlation was found for XO with SBP and DBP (p < 0.01). In regression analysis, the serum levels of XO showed a significant and independent association with hypertension prevalence. In conclusion, the mean level of serum XO was significantly higher in hypertensive individuals and XO was independently associated with the prevalence of hypertension. Our results indicate that XO may have a potential role in the pathophysiology of elevated blood pressure through generating of reactive oxygen species. Further large-scale longitudinal studies are needed to determine the underlying mechanisms between XO and hypertension.

Assessment of the relationship between serum xanthine oxidase levels and type 2 diabetes: a cross-sectional study

Xanthine oxidase (XO) is an enzyme associated with purine metabolism. The relationship between XO levels and type 2 diabetes (T2D) is not clear yet or little is known so far. Therefore, we conducted a cross-sectional study to determine the association of XO levels with T2D in a Bangladeshi adult cohort. A total of 325 participants (234 males and 91 females) were enrolled in the study. The participants were divided into three groups; diabetic (n = 173), prediabetic (n = 35), and non-diabetic control (n = 117). Serum levels of XO were measured by enzyme-linked immunosorbent assay (ELISA) and other biochemical parameters including fasting blood glucose (FBG), serum uric acid (SUA), and lipid profile markers measured by colorimetric methods. Participants with T2D were confirmed according to the definition of the American Diabetic Association. The association between serum XO levels and T2D was determined by logistic regression models. The mean level of serum XO was significantly higher in females (6.0 ± 3.7 U/L) compared to male (4.0 ± 2.8 U/L) participants (p < 0.001). In contrast, males had a higher mean level of SUA (6.1 ± 1.9 mg/dL) than female (4.4 ± 1.9 mg/dL) participants (p < 0.001). The mean level of XO was significantly higher in the diabetic group (5.8 ± 3.6 U/L) compared to the prediabetic (3.7 ± 1.9 U/L) and control (2.9 ± 1.8 U/L) groups (p < 0.001). On the other hand, the mean SUA concentration was significantly lower in the diabetic group than in the other two groups (p < 0.001). A significant increasing trend was observed for FBG levels across the XO quartiles (p < 0.001). A decreasing trend was found for SUA levels in the XO quartiles (p < 0.001). Serum levels of XO and SUA showed a positive and negative correlation with FBG, respectively. In regression analysis, serum XO levels showed an independent association with T2D. In conclusion, this study reports a positive and independent association between XO levels and T2D in Bangladeshi adults. Monitoring serum levels of XO may be useful in reducing the risk of T2D. Further research is needed to determine the underlying mechanisms of the association between elevated XO levels and T2D.