An Overview on the Role of Xanthine Oxidase Inhibitors in Gout Management

Alghamdi, Adnan Ali; Althumali, Jameel Sami; Almalki, M Meshal Mohammed; Almasoudi, Ahmad Saeed; Almuntashiri, Ali Hussain; Almuntashiri, Abdulaziz Hassan; Mohammed, Alkhrizi Ibrahim; Alkinani, Ashraf Ali; Almahdawi, Meshari Saeed; Mahzari, M Ali Hussain

doi:10.51847/rkcpaycprc

Cited by 5 publications

(4 citation statements)

References 49 publications

(61 reference statements)

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“…It is known that XO can also directly oxidize ascorbate [ 27 ]; however, ascorbate supplementation significantly protects the organism against XO hyperactivity [ 28 ]. Moreover, the latest studies show that due to the possibility of continuous supplementation with ascorbate, the resulting inhibition of XO activity in plasma significantly contributes to the improvement in gout treatment [ 29 , 30 , 31 , 32 ]. On the other hand, ascorbate has no effect on the activity of XO under physiological conditions, as found with skin cells (fibroblasts and keratinocytes).…”

Section: Antioxidant Propertiesmentioning

confidence: 99%

Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid

2022

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Ascorbic acid, as a one of the basic exogenous vitamins, occurs in the body in the form of ascorbate, known for its strong antioxidant and anti-inflammatory properties. The presented review shows not only the importance of ascorbate as a free radical scavenger but also summarizes its antioxidant action based on other mechanisms, including the activation of intracellular antioxidant systems and its effect on the NFκB/TNFα pathway and apoptosis. Ascorbate interacts with small-molecule antioxidants, including tocopherol, glutathione, and thioredoxin; it can also stimulate biosynthesis and the activation of antioxidant enzymes, such as superoxide dismutase, catalase, or glutathione peroxidase. Moreover, ascorbate promotes the activity of transcription factors (Nrf2, Ref-1, AP-1), which enables the expression of genes encoding antioxidant proteins. Additionally, it supports the action of other exogenous antioxidants, mainly polyphenols. In this regard, both DNA, proteins, and lipids are protected against oxidation, leading to an inflammatory reaction and even cell death. Although ascorbate has strong antioxidant properties, it can also have pro-oxidant effects in the presence of free transition metals. However, its role in the prevention of DNA mutation, inflammation, and cell apoptosis, especially in relation to cancer cells, is controversial.

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Section: Antioxidant Propertiesmentioning

confidence: 99%

Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid

2022

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“…However, to minimize the potential risk of AHS, the initial doses of allopurinol as monotherapy should not be over 100mg/day for any gout patient and 50mg/day for acute gout patients with either stage 4 or, worse, chronic kidney disease. As such, progressive titration every 2 to 5 weeks is recommended to ensure that dosages over 300mg/day may be utilized in acute gout patients with renal disease and impairment in cases accompanied by adequate monitoring and education of the patients [ 24 ]. Moreover, Ruoff and Edwards maintain that allele HLA-B5801 testing is vital before allopurinol initiation, particularly in patients with either stage 3 or worse chronic kidney disease, and that the use of allopurinol must be avoided in individuals who tested positive for the HLA-B5801 allele, owing to the increased risk of AHS [ 1 ].…”

Section: Reviewmentioning

confidence: 99%

“…Consequently, febuxostat does not need any adjustment or escalation of the renal dose, even as its usage has been reported not to have a comparable risk for AHS as allopurinol. Nonetheless, safety trials' preliminary outcomes have indicated an increment in cardiovascular mortality in instances where a febuxostat was compared against allopurinol [ 24 , 25 ]. The trial design was aimed at comparing the cardiovascular mortality rates, non-fatal stroke, non-fatal myocardial infarction, and unstable angina that needs critical coronary revascularization between allopurinol 200 to 600mg/daily and febuxostat 40 and 80mg/daily over a five-year duration [ 25 ].…”

Section: Reviewmentioning

confidence: 99%

“…Subsequently, another pivotal study that delved into the comparative effectiveness of monotherapy versus combination therapy for acute gout treatment was carried out by Dalbeth et al This 12-month investigation also sought to assess the safety and efficacy of the combined approach involving lesinurad and febuxostat in managing acute gout. Initial trials focusing on the combination therapy of lesinurad and febuxostat had already revealed more substantial reductions in serum urate levels compared to febuxostat monotherapy [ 24 ]. Consequently, the study enrolled adult patients experiencing acute gout who had previously been treated with serum urate-reducing agents or were treatment-naive.…”

Section: Reviewmentioning

confidence: 99%

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The Stiff Joint: Comparative Evaluation of Monotherapy and Combination Therapy With Urate Lowering Agents in Managing Acute Gout

Okobi,

Oletu,

Chukwuedozie-Echeazu

et al. 2023

Cureus

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Gout, an extremely painful form of arthritis, is triggered by the innate immune system's response to the accumulation of monosodium urate crystals in specific joints and surrounding tissues. This condition is characterized by recurring episodes of excruciating arthritis flares, interspersed with periods of disease quiescence. Over time, gout can result in disability, tophi formation, and severe pain. The treatment of gout is centered around two main objectives: alleviating inflammation and pain during acute gout attacks and long-term management to reduce serum urate levels and mitigate the risk of future attacks. Addressing inflammation and pain during acute attacks is often complicated by various factors, including underlying health conditions commonly associated with gout, such as hypertension, chronic kidney disease, cardiovascular disease, and diabetes mellitus. Moreover, gout patients are frequently older and have multiple coexisting health issues, necessitating complex medication regimens. Given the rising prevalence of gout and its associated comorbidities, there's a growing demand for improved treatment options. While existing treatments effectively manage gout in some patients, a significant portion, particularly those with comorbidities, face contraindications to these treatments and require alternative approaches. Innovative medications are required to enhance gout treatment, especially for individuals with concurrent health conditions. These considerations underscore the importance of reviewing both monotherapy and combination therapy approaches for acute gout treatment.

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