Uric Acid Formation Research Articles

Progress in modeling avian hyperuricemia and gout (Review).

Human organ tissue is vulnerable to hyperuricemia (HUA), which negatively impacts quality of life, particularly when it progresses to gout. Chicken uric acid formation and metabolism are similar to human uric acid metabolism; therefore, theoretically, the genesis and progression of human HUA and gout may be similar to those of poultry models. The present review explored HUA and gout and the progress of poultry-induced HUA and gout models. The present study reviewed procedures of modelling chicken gout and HUA and the detection indices and current concerns regarding these models. Notably, In the production of poultry hyperuricemia model, the combined method of water and food induction has a higher success rate and stability. Compared with mice induced HUA and gout models, poultry induced HUA and gout models had less kidney damage, and the models were stable and long-lasting.

Inhibitory mechanism of xanthine oxidase by 6-, 8- and 10-gingerol: Enzyme kinetics, multi-spectroscopy and molecular simulations

In this study, the inhibitory activity and mechanism of three gingerols (6-, 8- and 10-gingerol) on xanthine oxidase (XOD), a key enzyme responsible for the formation of uric acid, were evaluated. The three gingerols reversibly inhibited XOD activity in a mixed manner with IC50 values of (13.16 ± 0.41), (10.18 ± 0.22) and (6.88 ± 0.11) μM, respectively. 10-gingerol exhibited stronger inhibitory ability, which might contribute to its superior antioxidant properties, higher binding affinity and more significant conformational changes for XOD compared to other gingerols. Fluorescence quenching and molecular docking results indicated that gingerols acted in the vicinity of the flavin adenine dinucleotide in XOD, interacting with the surrounding key amino acid residues through hydrogen bonding and van der Waals forces, thereby preventing substrate entry and the release of catalytic products. Molecular dynamics simulations showed that the addition of gingerol decreased the stability and increased the structural density of XOD. These findings could provide valuable data for the application of gingerols in new XOD inhibitors and hypouricemic functional foods.

Chronic pyogenic spondylitis in patients with spinal gout: a case series and literature review

Background. Spinal gout is a rare and poorly described group of noninfectious inflammatory spinal lesions characterized by the deposition of monosodium urate crystals in the epidural space, paravertebral soft tissues, and by facet joints damage. There is no systematized data on the course of infectious spondylitis and spinal gout in the literature. The aim of the study — to present long-term outcomes of surgical treatment of chronic pyogenic spondylitis in patients with spinal gout and systematize the literature data on the issue. Methods. The clinical part of the study included 6 consecutively operated patients in the period from 2018 to 2021. The diagnosis of spinal gout and chronic pyogenic spondylitis was verified according to the results of histologic and bacteriologic studies of surgical material. Catamnesis accounted for at least 12 months. We studied the peculiarities of clinical and laboratory, radiological and histologic manifestations of the disease. Literature data systematization was carried out in the databases PubMed, Google Scholar, eLIBRARY from 2013 to 2023. Inclusion criteria: level of evidence II B-IV, catamnesis more or equal to 6 months, information on diagnostic and treatment measures. Results. The average age of the patients was 55±9 years. The duration of the diagnostic pause was 8±5 years. Multisegmented lesions of the lumbar (n = 6) spine prevailed. According to the classification of Pola E. et al. (2017) the following types of spondylitis were identified: B.3 (n = 1), C.1 (n = 1), C.3 (n = 2) and C.4 (n = 2). The clinical manifestation was dominated by chronic back pain with an intensity of 6,1±1,4 VAS scores. Neurologic disorders of the lower extremities and pelvic (ASIA scale) corresponded to types B (n = 1) and C (n = 4). The type of surgery: three-column reconstruction through combined approach in 2 cases and isolated anterior column reconstruction in 2 cases, 360° fusion in 1 case, and debridement of the epidural space and anterior column through posterior approach in 1 case. The follow-up results show the absence of recurrence of spondylitis in 4 cases, in 2 patients there were postoperative complications that required revision, after which no recurrence of spondylitis was noted. We selected 17 publications for literature review. Conclusion. The combination of chronic pyogenic spondylitis and spinal gout is a rare and poorly described pathology in the literature. Long therapeutic pause, chronic character of vertebrogenic pain syndrome in combination with increased uric acid level and formation of tophi of vertebral localization are distinctive features of the disease. Neurologic disorders with the combination of spondylitis and gout result from stenosis of the spinal canal due to two factors — epidural abscesses and tophi. Achieving local control of the combined pathology is possible with a combination of surgical intervention and long-term administration of hypouricemic drugs.

The effects of ecdysterone and enalapril on nitric oxide synthesis and the markers of oxidative stress in streptozotocin-induced diabetes in rats: a comparative study.

Cardiovascular functions in diabetes greatly depend on constitutive NOS (cNOS) activity. A comparative study of the effects of a steroid hormone ecdysterone and enalapril, an ACE inhibitor widely used to treat cardiac disorders on cNOS, inducible NOS (iNOS), xanthine oxidoreductase (XOR) activity, RNS, ROS, and lipid peroxidation in heart tissue in experimental diabetes was conducted. The rat model of diabetes was established by streptozotocin injection. NOS activity, NO2-, NO3-, uric acid, nitrosothiols, hydroperoxide, superoxide, and diene conjugate formation were studied spectrophotomerically. In diabetes, cNOS downregulation correlated with a dramatic fall of NO2- production and ~4.5-fold elevation of nitrosothiols, which agreed with a steep rise of iNOS activity, while NO3- remained close to control. Dramatic activation of XOR was observed, which correlated with the elevation of both superoxide production and nitrate reductase activity and resulted in strong lipid peroxidation. Ecdysterone and enalapril differently affected RNS metabolism. Ecdysterone moderately restored cNOS but strongly suppressed iNOS, which resulted in the reduction of NO3-, but full restoration of NO2- production. Enalapril better restored cNOS but less effectively suppressed iNOS, which promoted NO3- formation. Both drugs similarly inhibited XOR, which equally alleviated oxidative stress and lipid peroxidation. The synergistic action of iNOS and XOR was a plausible explanation for strong lipid peroxidation, abolished by the inhibition of iNOS and XOR by ecdysterone or enalapril. Complementary effects of ecdysterone and enalapril on cNOS, iNOS, and RNS are a promising basis for their combined use in the treatment of cardiovascular disorders caused by cNOS dysfunction in diabetes.

Features of formation of uric acid by Tribolium confusum Duv. (Tenebrionidae) in stored grain

Features of formation of uric acid by Tribolium confusum Duv. (Tenebrionidae) in stored grain

Xanthine Oxidoreductase in the Pathogenesis of Endothelial Dysfunction: An Update.

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the formation of uric acid (UA) and is involved in the generation of reactive oxygen species (ROS). Overproduction of ROS has been linked to the pathogenesis of hypertension, atherosclerosis, and cardiovascular disease, with multiple studies over the last 30 years demonstrating that XOR inhibition is beneficial. The involvement of XOR and its constituents in the advancement of chronic inflammation and ROS, which are responsible for endothelial dysfunction, is the focus of this evidence-based review. An overabundance of XOR products and ROS appears to drive the inflammatory response, resulting in significant endothelium damage. It has also been demonstrated that XOR activity and ED are connected. Diabetes, hypertension, and cardiovascular disease are all associated with endothelial dysfunction. ROS mainly modifies the activity of vascular cells and can be important in normal vascular physiology as well as the development of vascular disease. Suppressing XOR activity appears to decrease endothelial dysfunction, probably because it lessens the generation of reactive oxygen species and the oxidative stress brought on by XOR. Although there has long been a link between higher vascular XOR activity and worse clinical outcomes, new research suggests a different picture in which positive results are mediated by XOR enzymatic activity. Here in this study, we aimed to review the association between XOR and vascular endothelial dysfunction. The prevention and treatment approaches against vascular endothelial dysfunction in atherosclerotic disease.

Uric acid formation is driven by crosstalk between skeletal muscle and other cell types.

Hyperuricemia is implicated in numerous pathologies, but the mechanisms underlying uric acid production are poorly understood. Using a combination of mouse studies, cell culture studies, and human serum samples, we sought to determine the cellular source of uric acid. In mice, fasting and glucocorticoid treatment increased serum uric acid and uric acid release from ex vivo-incubated skeletal muscle. In vitro, glucocorticoids and the transcription factor FoxO3 increased purine nucleotide degradation and purine release from differentiated muscle cells, which coincided with the transcriptional upregulation of AMP deaminase 3, a rate-limiting enzyme in adenine nucleotide degradation. Heavy isotope tracing during coculture experiments revealed that oxidation of muscle purines to uric acid required their transfer from muscle cells to a cell type that expresses xanthine oxidoreductase, such as endothelial cells. Last, in healthy women, matched for age and body composition, serum uric acid was greater in individuals scoring below average on standard physical function assessments. Together, these studies reveal skeletal muscle purine degradation is an underlying driver of uric acid production, with the final step of uric acid production occurring primarily in a nonmuscle cell type. This suggests that skeletal muscle fiber purine degradation may represent a therapeutic target to reduce serum uric acid and treat numerous pathologies.

The Effect of Soursop Leaf Extract in Reducing Pain in Gout Arthritis

Gout arthritis is a disease characterized by pain caused by deposits of monosodium crystals that accumulate in the joints due to high levels of uric acid in the blood. Currently, pain management treatment for gout arthritis patients focuses on pharmacological treatment by providing analgesics to relieve pain. Soursop leaf extract has been proven to have an effect in reducing pain, but there has been no research regarding the effect of boiled soursop leaves to reduce it. The aim of this study was to analyze the effect of giving soursop leaf decoction on reducing pain in gout arthritis patients. The research used a quasi-experimental design with a one group pre-posttest design. The sample selected by using purposive sampling technique, totaling 18 people. The independent variable was soursop leaf decoction. The dependent variable was the pain in gout arthritis. The data analysis used the Wilcoxon Signed Ranks Test statistical test. The compounds contained in soursop leaves function as a strong analgesic (pain reliever) and have antioxidant properties. The antioxidant properties contained in soursop leaves can reduce the formation of uric acid by inhibiting the production of the enzyme xanthine oxidase. This combination of analgesic and anti-inflammatory properties can reduce gout. This study found that there was an effect of giving soursop leaf decoction on reducing pain in gout arthritis patients.

Prevalence of Hyperuricemia at a Tertiary Care Centre of Jumla, Nepal: A Retrospective Study

Background: Purines after its metabolism, gives rise to the formation of uric acid as an end product. More than 70% of its excretion is done by the renal system and lesser portion by intestinal and biliary system. Hyperuricemia is caused by the abnormalities in serum uric acid (SUA) metabolism and its impairment in renal function leading to the urate retention. Methods: Observational descriptive cross sectional study (retrospective chart review) done from 16th July 2021 to 15th July 2022 to determine the prevalence of hyperuricemia. The data entered in Microsoft Excel 2007 and analyzed in SPSS (statistical package for social sciences) version 16. Results: In this study, total participants were 1491 of which male was 553 (37.08%), and female was 938 (62.91%). Prevalence of hyperuricemia was 9.99% in the total population. 16.09% male and 6.39% female population were hyperuricemic. Conclusions: Besides various factors of the health hazards, hyperuricemia is also one of them and sometimes may go undiagnosed. Timely diagnosis and its treatment may protect against cardiovascular events, hypertension, renal disorders, etc.

Inhibitory capacity of extracts and main constituents of hop flowers

BackgroundHops (Humulus lupulus Linn.) produce flowers that are used on an industrial scale to impart sensory properties to beer and have some pharmacologic properties already published in the literature. Gout, type 2 diabetes and Alzheimer’s are diseases the appearance/aggravation of which is related to the action of enzymes such as xanthine oxidase, α-glucosidase and acetylcholinesterase, respectively, which are associated with oxidative stress. Our hypothesis is that the extracts and chemical constituents isolated from the flowers of hops act as enzyme inhibitors and scavenge free radicals. Hexane and methanol extracts were obtained from flowers of different cultivars produced in Brazil and from commercial pellets, with the contents of bitter acids and xanthohumol determined by high-performance liquid chromatography (HPLC), after QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction and were evaluated for their pharmacologic properties.ResultsThe extracts and analytical standards showed a significant capacity against oxidative stress in all evaluated methods (DPPH·, ABTS·+, HO·). Xanthohumol and extracts with a high concentration of this compound demonstrated a strong capacity to inhibit the xanthine oxidase and significantly reduce the formation of uric acid. The results with the α-glucosidase revealed promising pharmacologic action for all samples, even more effective than the commercial drug (acarbose). The acetylcholinesterase inhibition assays were effective for hexane extracts and ICE-4, with values obtained close to the eserine.ConclusionIt can be concluded with the results obtained that extracts and patterns of hop flowers showed promising potential to combat oxidative stress and complementary treatment of gout, type 2 diabetes and Alzheimer’s disease.

Amelioration of hyperuricemia by Lactobacillus acidophilus F02 with uric acid-lowering ability via modulation of NLRP3 inflammasome and gut microbiota homeostasis

Hyperuricemia is a metabolic disease caused by disturbances in purine metabolism and imbalances in the formation and excretion of uric acid. It is closely related to the gut microbiota, which is considered a therapeutic target. Some lactic acid bacteria with a uric acid lowering effect have the potential to ameliorate hyperuricemia in the host. However, the mechanism of action remains unclear. Here, we screened a strain of Lactobacillus acidophilus F02 that efficiently degrades uric acid precursors (inosine and guanosine) and further investigated its underlying mechanism on the alleviation of hyperuricemia in high fructose-adenine induced mice. Results showed that L. acidophilus F02 administration reduced serum uric acid levels in hyperuricemia mice by inhibiting xanthine oxidase and adenosine deaminase activity, while protecting hepatorenal injury and systemic inflammation by regulating the relative expression of NLRP3 inflammasome. Most importantly, it restored gut microbial homeostasis and the abundance of bacterial taxa (i.e., a balance in the relative abundance of Firmicutes and Actinobacteria and an increase in the abundance of Bacteroides, Ruminococcus and Lactobacillus). Furthermore, the ability of L. acidophilus F02 to lower uric acid and suppress NLRP3 inflammasome expression was confirmed in the HK-2 cell model, as well as the multiple immunomodulatory effects on RAW264.7 cells. Taken together, we speculate that fructose-adenine induced hyperuricemia triggers hepatorenal injury and gut microbiota dysbiosis, which is ameliorated by L. acidophilus F02. Collectively, the results suggest that lowering uric acid synthesis, increasing uric acid excretion and reducing NLRP3-related IL-1β levels are effective strategies to ameliorate hyperuricemia. Such information could inform future studies on the ecology of L. acidophilus and guide the use of this species for dietary applications in the food industry.

Uji Efektivitas Ekstrak Etanol Daun Kersen (Muntingia calabura L.) Sebagai Antihiperurisemia Pada Tikus Putih Jantan Yang Di Induksi Kalium Oksonat

Kersen plant (Muntingia calabura L.) is a plant that has many properties and is useful as medicine. Hyperuricemia is a condition where there is an increase in uric acid levels above normal. The leaf part of this plant is widely used by the community as a traditional medicine because of its metabolite compounds. Flavonoid compounds in cherry leaves can reduce uric acid levels through inhibition of the xanthine oxidase enzyme, an enzyme that acts as a catalyst in the oxidation process of hypoxanthine to xanthine and then to uric acid. By inhibiting the work of the xanthine oxidase enzyme, the formation of uric acid will also be inhibited. This study aims to determine the effectiveness of cherry leaf ethanol extract in reducing uric acid levels in male white rats induced by potassium oxonate. This study used an experimental method using 25 male white rats induced by potassium oxonate. The test animals were divided into 5 groups: negative control (CMC Na 1%), positive control (Allopurinol), EEDK dose of 300 mg/kgBB, EEDK dose of 400 mg/kgBB, EEDK dose of 500 mg/kgBB. Measurement of uric acid levels in rats using the point of care testing (POCT) method. All data obtained were analyzed statistically using the One Way Anova test. The results of the analysis showed that there were significant differences between the negative control, positive control, EEDK 300 mg/kg, EEDK 400 mg/kg, and EEDK 500 mg/kg (P<0.05). The most effective dose of cherry leaf ethanol extract as an antihyperuricemia is the EEDK dose of 500 mg/kg BW. There was no significant difference between EEDK 400 mg/kgBW, EEDK 500 mg/kgBW and positive control (P>0.05). Based on the results of the analysis that has been done, it can be concluded that the ethanol extract of cherry leaves has an antihyperuricemia effect in rats. Keywords: Cherry leaves, Hyperuricemia, Potassium oxonate

Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice

Backgroundα-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PurposeThe current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. MethodsThe effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. Resultsα-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. Conclusionsα-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Association between serum uric acid concentration and radiographic axial spondylarthritis: a cross-sectional study of 202 patients.

Association between serum uric acid concentration and radiographic axial spondylarthritis: a cross-sectional study of 202 patients.

Investigations on melamine-based uric acid kidney stone formation and its prevention by inhibitors.

Melamine (Mel) as a milk powder adulterant came to light in September 2008, when a kidney stone disease (KSD) outbreak struck China. The mechanism of the formation of Mel-associated uric acid (UA) stones is relatively unknown. Therefore, in the present study, Mel's influence was explored at comparatively higher and lower concentrations in artificial urine. The parameter optimization performed when the Mel concentration in artificial urine was low, which revealed that higher pH values and lower UA concentration considerably delayed the induction of UA crystallization. When Mel concentration was increased relative to UA concentration, the induction time of UA crystallization decreased dramatically. At the highest concentration of Mel investigated (at UA-Mel molar ratio 1:1), PXRD analysis and SEM revealed a change in crystalline structure of the samples. Based on FTIR analysis, it was determined that UA-Mel interactions are essentially physical, because no new characteristic bands developed. Two inhibitors, namely tri-potassium citrate (TPC) and 3, 7-dimethylxanthine (DMX), were investigated for their inhibitory action on UA crystallization in the presence of Mel. DMX was observed to be more promising than TPC in delaying the induction of crystallisation and hence inhibiting crystal formation.

Probing the Interactions of 31 Mycotoxins with Xanthine Oxidase: Alternariol, Alternariol-3-Sulfate, and α-Zearalenol Are Allosteric Inhibitors of the Enzyme.

Mycotoxins are frequent toxic contaminants in foods and beverages, causing a significant health threat. Interactions of mycotoxins with biotransformation enzymes (e.g., cytochrome P450 enzymes, sulfotransferases, and uridine 5'-diphospho-glucuronosyltransferases) may be important due to their possible detoxification or toxic activation during enzymatic processes. Furthermore, mycotoxin-induced enzyme inhibition may affect the biotransformation of other molecules. A recent study described the strong inhibitory effects of alternariol and alternariol-9-methylether on the xanthine oxidase (XO) enzyme. Therefore, we aimed to test the impacts of 31 mycotoxins (including the masked/modified derivatives of alternariol and alternariol-9-methylether) on XO-catalyzed uric acid formation. Besides the in vitro enzyme incubation assays, mycotoxin depletion experiments and modeling studies were performed. Among the mycotoxins tested, alternariol, alternariol-3-sulfate, and α-zearalenol showed moderate inhibitory actions on the enzyme, representing more than tenfold weaker impacts compared with the positive control inhibitor allopurinol. In mycotoxin depletion assays, XO did not affect the concentrations of alternariol, alternariol-3-sulfate, and α-zearalenol in the incubates; thus, these compounds are inhibitors but not substrates of the enzyme. Experimental data and modeling studies suggest the reversible, allosteric inhibition of XO by these three mycotoxins. Our results help the better understanding of the toxicokinetic interactions of mycotoxins.

In vitro inhibition of xanthine oxidase by hydroalcoholic extracts of Corynaea crassa Hook. F

Corynaea crassa is a hemiparasitic plant native to America, used for the treatment of erectile dysfunction and has been shown to have antimicrobial properties. However, it lacks other biological studies to justify its use in traditional medicine. The objective was to examine the in vitro inhibitory activity of xanthine oxidase in hydroalcoholic extracts of the species from Ecuador and Peru. The extracts obtained by maceration and the Allopurinol used as the reference drug, at concentrations of 10, 30, 40, 50 and 60 µg/mL, were tested to measure the degree of in vitro inhibition of xanthine oxidase employing spectrophotometric determination at 295nm, which is associated with the formation of uric acid. The two extracts showed significant inhibitory activity on xanthine oxidase in a concentration-dependent manner, with the highest percentages being observed at the highest concentrations, being higher for the extract from the Ecuadorian species with enzyme inhibition percentages comparable to Allopurinol. Median inhibitory concentration (IC50) values ​​of 15.35µg/mL and 17.42µg/mL were observed for the extracts from Ecuador and Peru, respectively, although the activity was more notable for the reference drug, which was shown to be an IC50 of 12.21 µg/mL. The results concluded the basis for the potential use of C. crassa in the treatment of hyperuricemia. Keywords: xanthine oxidase, hydroalcoholic extracts, Allopurinol

In vivo anti-hyperuricemia and anti-gouty arthritis effects of the ethanol extract from Amomumvillosum Lour.

The incidence of hyperuricemia and gout has been increasing year by year, and it is showing a younger trend. However, the first-line drugs currently used for hyperuricemia and gouty arthritis have serious side effects that limit their clinical application. Amomum villosum Lour. has been widely used in China for thousands of years as a traditional medical and edible plant, and previous screening showed that the ethanol extract of Amomum villosum Lour. could effectively inhibit the activity of xanthine oxidase. Based on this discovery, this paper had achieved in-depth mechanism research. The results showed that the ethanol extract of Amomum villosum Lour. could treat hyperuricemia by reducing the production of uric acid via inhibition of xanthine oxidase and increasing the excretion of uric acid via regulation of urate transporters. Meanwhile, the extract also showed a certain protective effect on hepatic and renal damage caused by hyperuricemia. With the formation of extensive uric acid, gouty arthritis will be induced by the deposition of monosodium urate in the joint. The extract could also relieve the inflammation by reducing the expression of inflammatory cytokines. In conclusion, the extract deserves focused research and development as a potential medicine, health care product or supplemented food for the prevention and treatment of hyperuricemia and gouty arthritis.

Potential Activity of Caryophyllene Derivatives as Xanthine Oxidase Inhibitor: An in silico Quantitative Structure-Activity Relationship Analysis

As the enzyme responsible for the uric acid formation, Xanthine oxidase was considered to be a therapeutic target for hyperuricemic treatment. This study was carried out to assess the potential of caryophyllene, and its derivates usually present in the natural product to inhibit Xanthine oxidase. The molecular docking using Autodock Tool and Biovia Discovery Studio was conducted to visualize the molecular interaction and to reveal the structure-activity relationship of those compounds. The results showed that the derivates of caryophyllene showed a higher affinity to Xanthine Oxide than Allopurinol. Among those all, caryophyllene oxide has the most stable bonding to xanthine oxide. Structure-activity relationship analysis showed that the chemical properties of the compound affected the affinity and molecular interaction to the enzyme as the target site in this study. The number of double bonds, substituents position, conformational structure related to steric hindrance, and the presence of lactone ring were assumed to influence the xanthine oxide inhibitory activity of caryophyllene derivates.

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.