Xanthine oxidoreductase and its inhibitors: relevance for gout

2016 ◽  
Vol 130 (23) ◽  
pp. 2167-2180 ◽  
Author(s):  
Richard O. Day ◽  
Bishoy Kamel ◽  
Diluk R.W. Kannangara ◽  
Kenneth M. Williams ◽  
Garry G. Graham
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidoreductase ◽  
Monosodium Urate ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Saturation Point ◽  
First Line Therapy ◽  
And Function ◽  
Rate Limiting ◽  
Over 40 Years ◽  
Urate Crystals

Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism and converts hypoxanthine to xanthine, and xanthine into uric acid. When concentrations of uric acid exceed its biochemical saturation point, crystals of uric acid, in the form of monosodium urate, emerge and can predispose an individual to gout, the commonest form of inflammatory arthritis in men aged over 40 years. XOR inhibitors are primarily used in the treatment of gout, reducing the formation of uric acid and thereby, preventing the formation of monosodium urate crystals. Allopurinol is established as first-line therapy for gout; a newer alternative, febuxostat, is used in patients unable to tolerate allopurinol. This review provides an overview of gout, a detailed analysis of the structure and function of XOR, discussion on the pharmacokinetics and pharmacodynamics of XOR inhibitors–allopurinol and febuxostat, and the relevance of XOR in common comorbidities of gout.

Biostatistical Analysis and Possible Forecasting of Relationship Between Uric Acid and Specific Laboratory Tests in Cases of Gouty Arthritis

2017 ◽  
Vol 68 (6) ◽  
pp. 1234-1241
Author(s):  
Adina Octavia Duse ◽  
Delia Berceanu Vaduva ◽  
Mirela Nicolov ◽  
Cristina Trandafirescu ◽  
Marcel Berceanu Vaduva ◽  
...  
Keyword(s):  
Uric Acid ◽  
Laboratory Tests ◽  
Gouty Arthritis ◽  
Main Diagnosis ◽  
Monosodium Urate ◽  
Glutamate Pyruvate ◽  
Metatarsophalangeal Joints ◽  
The Relationship ◽  
Biostatistical Analysis ◽  
Urate Crystals

Acute gouty arthritis represents an inflammatory response to microcrystals of monosodium urate that precipitate in joint tissues from supersaturated body fluids or are shed from preexisting articular deposits [1]. Gout is a metabolic disease characterized by recurrent episodes of arthritis associated with the presence of monosodium urate crystals in the tissue or synovial fluid during the attack.These forms of crystal-induced arthritis usually affect peripheral joints, including knee, ankle, wrist, and metacarpophalangeal and metatarsophalangeal joints. All of them may be associated with other inflammatory, endocrine diseases [2]. The present study was done to highlight the relationship between increased levels of uric acid and specific laboratory tests in order to possible forecast development of further disease in patients with gouty arthrithis.The present study was done on 34 patients hospitalized in Felix Hospital of Rehabilitation in 2015-2016, with age between 44 and 74, having the main diagnosis of gouty arthritis.We studied the following laboratory tests:urea and other related analysis, like uric acid, creatinine, cholesterol, glutamate pyruvate transaminase and glutamate oxalate transaminase.

scholarly journals Tu-Teng-Cao Extract Alleviates Monosodium Urate-Induced Acute Gouty Arthritis in Rats by Inhibiting Uric Acid and Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rongmei Yao ◽  
Zihan Geng ◽  
Xin Mao ◽  
Yanyan Bao ◽  
Shanshan Guo ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gouty Arthritis ◽  
Histological Evaluation ◽  
Therapeutic Effects ◽  
Monosodium Urate ◽  
Cell Degeneration ◽  
Acute Gouty Arthritis ◽  
Monosodium Urate Crystals ◽  
Potassium Oxonate ◽  
Urate Crystals

Gouty arthritis is an inflammatory joint disease closely related to hyperuricemia. It is characterized by deposition of monosodium urate crystals in the joints, resulting in an intense inflammatory process and pain. Control of hyperuricemia and anti-inflammation treatments are the main therapeutic approaches. However, the commonly used drugs for inhibiting uric acid and acute gouty arthritis have obvious gastrointestinal and renal toxicity; thus, there is an urgency to develop new alternative therapeutic drugs. An extract of Tu-Teng-Cao (TTC), a compound drug used in traditional Chinese medicine, has been widely applied to the clinical treatment of arthritis. In this study, we investigated the therapeutic effects of TTC on gouty arthritis. In this study, an animal model of acute gouty arthritis with hyperuricemia was established using potassium oxonate and monosodium urate crystals. After treatment with TTC, the results showed obvious therapeutic effects on the rat model of acute gouty arthritis. The treatment significantly attenuated the degree of ankle swelling, inflammation, and dysfunction index, and the levels of proinflammatory cytokines. In addition, TTC has significant antihyperuricemia activity in rats with hyperuricemia induced by potassium oxonate. Histological evaluation showed that TTC relieved pathological damage in rats with acute gouty arthritis induced by monosodium urate crystals. All the groups treated with TTC showed improvement in cartilage degeneration, cell degeneration, synovial hyperplasia, and inflammatory cell invasion in the ankle joint of rats. TTC significantly alleviated swelling, inflammation, and bleeding of the renal corpuscle and convoluted tubules of rats. The results of this study suggest that TTC is capable of treating gouty arthritis and decreasing ankle injury through the control of uric acid and inflammation.

THU0023 Soluble Uric Acid Exerts a Suppressive Effect on the Response of Macrophages to Monosodium Urate Crystals

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 201.1-201
Author(s):  
E. Garcia-Melchor ◽  
M. Guma ◽  
J. Yagüe ◽  
M. Juan ◽  
J. Harper
Keyword(s):  
Uric Acid ◽  
Suppressive Effect ◽  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Urate Crystals

scholarly journals Bilateral elbow indirect Cubital tunnel syndrome due to mass effect of Gouty tophi

2021 ◽  
Vol 13 (4) ◽  
pp. 70-73
Author(s):  
Akshay Lekhi
Keyword(s):  
Uric Acid ◽  
Case Reports ◽  
Surgical Excision ◽  
Mass Effect ◽  
Cubital Tunnel Syndrome ◽  
Pharmaceutical Drugs ◽  
Monosodium Urate ◽  
Tophaceous Gout ◽  
Tunnel Syndrome ◽  
Urate Crystals

Gout is an inflammatory arthritis associated with raised uric acid levels in blood. The pathology involves infiltration and destruction of ligament, cartilage, tendons, bone and skin by deposition of urate crystals. Our purpose of writing this case is to report rare bilateral neurological symptoms due to compression, by tophaceous gout around elbows. A 32-year-old male had presented with episodic tingling in bilateral ulnar nerve distributions for fourteen days. Surgical excision of the tophi around elbows that were causing the neural compression symptoms was done and symptoms relieved gradually over 6 weeks. Tophi are late presentations. They can present with symptoms from depositing at different sites that is evidenced in existing literature case reports. Controlling serum uric acid levels below deposition threshold either by dietary or pharmaceutical drugs is the mainstay of management, resulting in dissolution of monosodium urate crystals.

A case of severe gouty tophi-induced carpal tunnel syndrome: Operative finding and its outcome

2018 ◽  
Vol 50 (01) ◽  
pp. 19-21 ◽  
Author(s):  
Jun-Ku Lee ◽  
Ju Won Kim ◽  
Yoon Seok Kim ◽  
Bon San Koo
Keyword(s):  
Uric Acid ◽  
Severe Pain ◽  
Functional Disability ◽  
Soft Tissues ◽  
Joint Motion ◽  
Monosodium Urate ◽  
Joint Deformity ◽  
Tunnel Syndrome ◽  
Synovial Tissues ◽  
Urate Crystals

IntroductionGout is a disease featuring acute arthritis, joint deformity and severe pain caused through the deposition of monosodium urate crystals in and around synovial tissue 1. Tophi are stone-like deposits of monosodium urate in the soft tissues, synovial tissues, or bones adjacent to the joints. The tophi can compromise joint motion and deteriorate bony structure, finally leading to functional disability. Therefore, early treatment using uric acid lowering agents is standard practice in gout patients to prevent the formation of tophi through controlling uric acid levels.

scholarly journals HIPERURISEMIA DAN RESPONS IMUN

2013 ◽  
Vol 3 (2) ◽  
Author(s):  
Aaltje E. Manampiring
Keyword(s):  
Uric Acid ◽  
Essential Role ◽  
Adult Population ◽  
Monosodium Urate ◽  
Metabolic Disturbances ◽  
Monosodium Urate Crystals ◽  
Cytokines And Chemokines ◽  
Urate Crystal ◽  
Urate Crystals

Abstract: Hyperuricemia, a highly prevalent condition in adult population, is associated with hemodynamic and metabolic disturbances. Albeit, pathophysiological aspects of hyperuricemia are still not clearly understood. Uric acid plays an essential role in immunity by induction of some cytokines and chemokines, such as TNFα, Il-1β, IL-6, CXCL8 (IL-8), and CXCL1 (growth-related oncogene α). Deposits of monosodium urate crystals in joint cavities and periarticular tissues  are related to an autoinflammatory disturbance, namely gout. Keywords: hyperuricemia, monosodium urate crystal, immune responsse.   Abstrak: Hiperurisemia merupakan suatu keadaan yang umum dijumpai pada populasi dewasa dan berhubungan dengan kelainan metabolik dan hemodinamik. Aspek patofisiologik dari hiperurisemia belum sepenuhnya dipahami dengan jelas. Asam urat berperan penting dalam imunitas dengan menginduksi berbagai sitokin dan kemokin, antara lain TNFα, Il-1β, IL-6, CXCL8 (IL-8) dan CXCL1 (growth-related oncogene α). Deposit kristal monosodium urat di dalam rongga sendi dan jaringan periartikuler berkaitan dengan gangguan autoinflamasi yang dikenal sebagai gout. Kata kunci: hiperurisemia, kristal monosodium urat, respons imun.

scholarly journals Modified Chuanhu anti-gout mixture, a traditional Chinese medicine, protects against potassium oxonate-induced hyperuricemia and renal dysfunction in mice

2019 ◽  
Vol 47 (5) ◽  
pp. 1927-1935 ◽  
Author(s):  
Wenjun You ◽  
Jie Wang ◽  
Yaowu Zou ◽  
Kui Che ◽  
Xu Hou ◽  
...  
Keyword(s):  
Uric Acid ◽  
Underlying Mechanism ◽  
Joint Space ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Acute Gout ◽  
Mrna Levels ◽  
Monosodium Urate ◽  
Potassium Oxonate ◽  
Urate Crystals

Objective Acute gout is a painful, inflammatory arthritis that features a rapidly escalating inflammatory response resulting from the formation of monosodium urate crystals in the affected joint space. Previously, we found that Chuanhu anti-gout mixture (CAGM) had similar effects as colchicine against gout in the clinic. Subsequently, to improve its effectiveness and efficacy, we modified the original formulation of CAGM. The current study evaluated the effectiveness of the modified formulation in mice. Methods Potassium oxonate (PO) was used to establish a mouse model of hyperuricemia. Plasma levels of uric acid and creatine were determined using the respective test kits. Hepatic xanthine oxidase (XOD) expression was examined by enzyme-linked immunosorbent assay. To explore the underlying mechanism, renal urate transporter 1 (URAT1) mRNA levels were evaluated by quantitative real-time PCR. Allopurinol and benzbromarone were used as reference drugs. Results The original CAGM and its modified high-dose formulation significantly reduced serum uric acid and creatine levels in hyperuricemic mice. In addition, the CAGM-treated groups displayed lower mRNA levels of hepatic XOD and renal URAT1. Conclusions CAGM and its modified formulation significantly ameliorated PO-induced hyperuricemia in mice, which might be partially attributable to reductions of hepatic XOD and renal URAT1 levels.

Monosodium urate crystals inhibit tenocyte viability and function: implications for periarticular involvement in chronic gout

2013 ◽  
Author(s):  
Ashika Chhana ◽  
Karen Callon ◽  
Michael Dray ◽  
Bregina Pool ◽  
Dorit Naot ◽  
...  
Keyword(s):  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Chronic Gout ◽  
And Function ◽  
Urate Crystals

Management of Vatarakta w.s.r. to Gout through Panchakarma

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Dr. Chandramohan Arya ◽  
Dr.Sanjay Gupta
Keyword(s):  
Metabolic Disorders ◽  
Molecular Level ◽  
Modern Science ◽  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Predominant Symptom ◽  
Essential Components ◽  
Unique Approach ◽  
Ayurvedic Treatment ◽  
Urate Crystals

Vatarakta is more distressing and common metabolic disorder prevalent in present era. It is Vatapradhana Tridoshaja Vatavyadhi where Rakta is main Dushya. Vata is a predominant Dosha in Vatarakta, when it is excessively aggravated with vitiated Rakta is called Vatarakta. Vatarakta is correlated with gout in modern science. Gout is an abnormality of purine metabolism causes hyperuricemia and deposition of monosodium urate crystals in joints. Pain is predominant symptom of gout, which disturbs day-today life of the patients. The Panchakarma is not only a important component of Ayurvedic treatment but it is also forms the fundamental basis of Ayurveda therapy. The different procedures like Swedana, Vamana, Virechana, Basti, Sirovirechana, Raktamokshana focus on the purification which detoxifies the human body, i.e. the correction of the metabolism at molecular level. These detoxification procedures are essential components of the management in various metabolic disorders. So Panchakarma is an unique approach in the management of Vatarakta.

scholarly journals Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease

2021 ◽  
Author(s):  
Vitalii Kryvenko ◽  
Olga Vagin ◽  
Laura A. Dada ◽  
Jacob I. Sznajder ◽  
István Vadász
Keyword(s):  
Endoplasmic Reticulum ◽  
Intracellular Signaling ◽  
Loss Of Function ◽  
Α Subunit ◽  
Rate Limiting Step ◽  
Atpase Subunits ◽  
A Cell ◽  
Health And Disease ◽  
And Function ◽  
Rate Limiting

Abstract The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+ and K+ ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions. Graphic Abstract

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