BACKGROUND: Over the past two decades, the global incidence of gout has markedly increased, affecting people worldwide. Considering the side effects of xanthine oxidase (XO) inhibitor drugs (e.g. allopurinol and febuxostat) used in the treatment of hyperuricemia and gout, the potential application of phytochemicals has been widely studied. In addition, XO also takes part in the elimination of certain drugs, including 6-mercaptopurine. In the current explorative study, we aimed to examine the potential effects of tea catechins, resveratrol, silymarin flavonolignans and some of their conjugated metabolites on XO-catalyzed xanthine and 6-mercaptopurine oxidation, applying in vitro assays and modeling studies. RESULTS: Catechins, resveratrol and resveratrol conjugates exerted no or only weak inhibitory effects on XO. Silybin A, silybin B and isosilybin A were weak, silychristin was a moderate, while 2,3-dehydrosilychristin was a potent inhibitor of the enzyme. Sulfate metabolites of silybin A, silybin B and isosilybin A were considerably stronger inhibitors compared to the parent flavonolignans, and the sulfation of 2,3-dehydrosilychristin slightly increased its inhibitory potency. Silychristin was the sole flavonolignan tested, where sulfate conjugation decreased its inhibitory effect. CONCLUSION: 2,3-Dehydrosilychristin seems to be a promising candidate for examining its in vivo antihyperuricemic effects, because both the parent compound and its sulfate conjugate are highly potent inhibitors of XO. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
- MeSH
- Enzyme Inhibitors * chemistry pharmacology MeSH
- Catalysis MeSH
- Catechin * chemistry analogs & derivatives pharmacology MeSH
- Humans MeSH
- Mercaptopurine * chemistry pharmacology metabolism MeSH
- Oxidation-Reduction * MeSH
- Resveratrol * chemistry pharmacology MeSH
- Silymarin * pharmacology chemistry MeSH
- Xanthine chemistry metabolism pharmacology MeSH
- Xanthine Oxidase * antagonists & inhibitors metabolism chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Gout and hyperuricemia increase cardiovascular disease risk, highlighting the need for improved risk stratification. In this pilot study, we evaluated the Coronary Event Risk Test (CERT) in 94 hyperuricemic and 196 gout patients, and 53 controls. Plasma ceramides were determined by liquid chromatography-mass spectrometry. Elevated CERT scores (≥7) occurred in 11.7 % (2-fold increase) of hyperuricemic and 31.12 % (5.5-fold increase) of gout patients compared to controls. Additionally, both hyperuricemic and gout patients with increased CERT also exhibited higher levels of inflammation and atherogenic index of plasma, both of which were significantly associated with CERT. Incorporating CERT into routine care may enhance risk stratification and guide targeted interventions in this patient population.
- MeSH
- Biomarkers blood MeSH
- Ceramides * blood MeSH
- Chromatography, Liquid MeSH
- Gout * blood diagnosis complications MeSH
- Adult MeSH
- Risk Assessment MeSH
- Hyperuricemia * blood diagnosis complications MeSH
- Cardiovascular Diseases * diagnosis blood etiology epidemiology MeSH
- Uric Acid * blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Decision Support Techniques * MeSH
- Pilot Projects MeSH
- Predictive Value of Tests MeSH
- Prognosis MeSH
- Heart Disease Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Hyperurikemie se vyskytuje u 60 % pacientů s chronickým onemocněním ledvin (CKD) a dna asi u 25 % těchto pacientů. I přes častý společný výskyt není vliv kyseliny močové na progresi onemocnění ledvin jednoznačně objasněn. O indika- cích k léčbě asymptomatické urikemie u pacientů s CKD se vedou spory. Převaha důkazů naznačuje, že asymptomatická hyperurikemie je pravděpodobně škodlivá, ale může se týkat zejména určitých podskupin pacientů, a to pacientů se systémovými depozity urátu, urátovou krystalurií nebo urolitiázou a pacientů s vysokou intracelulární hladinou kyseliny močové. Současné důkazy nepodporují nasazení inhibitorů xantinoxidázy ke zmírnění progrese CKD u pacientů s asymp- tomatickou hyperurikemií.
Hyperuricaemia occurs in 60% of patients with chronic kidney disease (CKD) and gout in about 25% of these patients. Despite the frequent co-occurrence, the influence of uric acid on the progression of kidney disease is not clearly understood. There is controversy over the indications for treatment of asymptomatic uricemia in patients with CKD. The preponderance of evidence suggests that asymptomatic hyperuricaemia is likely to be harmful, but may be particularly relevant to certain subgroups of patients, namely those with systemic crystal deposits, urate crystalluria or urolithiasis, and those with high intracellular uric acid levels. Current evidence does not support the deployment of xanthine oxidase inhibitors to ameliorate the progression of CKD in patients with asymptomatic hyperuricaemia.
- MeSH
- Acute Kidney Injury etiology therapy MeSH
- Renal Insufficiency, Chronic * diagnosis etiology drug therapy MeSH
- Hyperuricemia diagnosis drug therapy complications MeSH
- Clinical Studies as Topic MeSH
- Uric Acid blood MeSH
- Humans MeSH
- Kidney Diseases etiology MeSH
- Xanthine Oxidase antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
Kyselina močová (UA) se převážně tvoří v játrech, střevech a cévním endotelu jako konečný produkt metabolismu purinů získaných exogenně z potravy a endogenně z poškozených nebo mrtvých buněk. Ledviny hrají hlavní roli ve vylučování UA, eliminují asi 70 % denní produkce. Zbytek (přibližně 30 %) je vylučován střevem. Pokud tvorba UA překračuje její vylučování, vzniká hyperurikemie. Hyperurikemie je silně spojena s rozvojem a závažností metabolického syndromu. Nadměrná exprese urátového transportéru 1 (URAT1) a glukózového transportéru 9 (GLUT9) a narušení glykolýzy kvůli inzulinové rezistenci mohou souviset s rozvojem hyperurikemie u metabolického syndromu. Dříve se hyperurikemie po- važovala pouze za hlavní příčinu dny a dnavé artritidy. Také se předpokládalo, že hyperurikemie u pacientů s renálními onemocněními je důsledkem nedostatečného vylučování UA kvůli ledvinnému selhání, a proto nebyla cílem intenzivní léčby. Základní vědecké poznatky nyní naznačují, že hyperurikemie hraje patogenní roli při vzniku chronického onemocnění ledvin a kardiovaskulárních onemocnění, protože způsobuje endoteliální dysfunkci, proliferaci cévních hladkých svalových buněk a aktivaci renin-angiotenzinového systému. Další nashromážděné údaje naznačují, že léčba snižující hladinu UA zpomaluje progresi těchto onemocnění. Snížení hladiny UA je účinnou metodou pro zlepšení stavu, ale ne všechny látky snižující hladinu UA fungují stejně. V klinické praxi je třeba tyto látky používat s opatrností.
Uric acid (UA) is predominantly formed in the liver, intestine and vascular endothelium as an end product of the metabolism of purines derived from food and endogenously from damaged or dead cells. The kidneys play a major role in the excretion of UA, eliminating about 70 % of the daily production. The remainder (approximately 30 %) is excreted by the intestine. If the production of UA exceeds the capacity of its excretion, hyperuricaemia results. Overexpression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9) and impaired glycolysis due to insulin resistance may be related to the development of hyperuricaemia in metabolic syndrome. Hyperuricemia is associated with the development and severity of metabolic syndrome. Previously, hyperuricaemia was thought to be the main cause of gout and gouty arthritis only. It was also assumed that hyperuricemia in patients with renal disease was a consequence of inadequate UA excretion due to renal failure and therefore was not a target for intensive treatment. Basic scientific evidence now suggests that hyperuricemia plays a pathogenic role in the development of chronic kidney disease and cardiovascular disease by causing endothelial dysfunction, vascular smooth muscle cell proliferation, and activation of the renin- angiotensin system. Lowering UA levels is an effective method for improving the condition, but not all UA lowering agents work the same. In clinical practice, these agents should be used with caution. Further accumulating data suggest that UA-lowering therapy slows the progression of these diseases.
- MeSH
- Allopurinol administration & dosage therapeutic use MeSH
- Gout Suppressants antagonists & inhibitors pharmacology therapeutic use MeSH
- Febuxostat administration & dosage therapeutic use MeSH
- Hyperuricemia drug therapy complications MeSH
- Cardiovascular Diseases prevention & control MeSH
- Uric Acid blood MeSH
- Humans MeSH
- Metabolic Syndrome * diagnosis etiology therapy MeSH
- Check Tag
- Humans MeSH
Předložený text stručně charakterizuje základní možnosti farmakoterapeutického ovlivnění hyperurikemie. Stále nejčastěji využívanou léčivou látkou v dané indikaci je alopurinol působící jako kompetitivní inhibitor xanthinoxidázy s potenciálem využití přesahujícím rámec pouhého ovlivnění urikemie. Stručně zmíněny jsou rovněž další látky, jakkoliv mnohé z nich nejsou aktuálně v ČR dostupné.
The presented text briefly characterizes the basic possibilities of pharmacotherapeutic treatment of hyperuricemia. Allopurinol acting as a competitive xanthine oxidase inhibitor with a potential for use beyond the mere influence of uricemia is still the most commonly used active substance in this indication. Other substances are also briefly mentioned, although many of them are not currently available in the Czech Republic.
- MeSH
- Allopurinol administration & dosage pharmacology adverse effects MeSH
- Gout Suppressants * administration & dosage pharmacology adverse effects MeSH
- Febuxostat administration & dosage pharmacology adverse effects MeSH
- Hyperuricemia drug therapy MeSH
- Uric Acid MeSH
- Humans MeSH
- Uricosuric Agents MeSH
- Check Tag
- Humans MeSH
Krystaly indukované artropatie vznikají ukládáním depozit krystalů v kloubních strukturách. Nejčastěji se v klinické praxi setkáváme s ukládáním krystalů urátu sodného, což je příčinou dnavé artritis. Dnavá artritis v dospělosti představuje jedno z nejčastějších zánětlivých kloubních postižení. Zejména pak v rozvinuté části světa, kde v posledních letech vidíme trend k nárůstu tohoto onemocnění. Hlavní rizikový faktor pro vznik dnavé artritis představuje hyperurikemie, tedy patologické zvýšení hladiny kyseliny močové v krvi. Dnavá artritis ovlivňuje kvalitu života pacientů nejenom výraznou bolestivostí, ale i poměrně úzkým vztahem ke kardiovaskulárním komplikacím. V terapii využíváme jak farmakologické, tak nefarmakolo- gické postupy. Do komplexní terapie je nutno zahrnout i kontrolu systémových rizik choroby.
Crystal-induced arthropathy is caused by the deposition of crystal deposits in joint structures. Most often in clinical practice we encounter the deposition of sodium urate crystals, which is the cause of gouty arthritis. Gouty arthritis in adulthood is one of the most common inflammatory joint disorders. Especially in the developed part of the world, where in recent years we have seen a trend towards an increase in this disease. The main risk factor for the development of gouty arthritis is hyperuricemia, i.e. a pathological increase in the level of uric acid in the blood. Gouty arthritis affects the quality of life of patients not only by significant pain, but also by a relatively close relationship to cardiovascular complications. In therapy, we use both pharmacological and non-pharmacological procedures. Control of the systemic risks of the disease must also be included in the comprehensive therapy.
Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies.
- MeSH
- Genome-Wide Association Study * MeSH
- Gout * genetics MeSH
- Genetic Predisposition to Disease * MeSH
- Hyperuricemia genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Uric Acid * MeSH
- Humans MeSH
- Mendelian Randomization Analysis MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Child MeSH
- Lesch-Nyhan Syndrome * nursing MeSH
- Humans MeSH
- Respite Care MeSH
- Children with Disabilities MeSH
- Social Work MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Medication Adherence * MeSH
- Allopurinol * therapeutic use MeSH
- Gout Suppressants * therapeutic use MeSH
- Gout drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Oxypurinol * therapeutic use MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Letter MeSH
- MeSH
- ATP Binding Cassette Transporter, Subfamily G, Member 2 genetics MeSH
- Blood Group Antigens * MeSH
- Cell Membrane metabolism MeSH
- Humans MeSH
- Neoplasm Proteins genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Letter MeSH
