Studies on the Effect of Probenecid (`Benemid') in Gout

Mason, R. M.

doi:10.1136/ard.13.2.120

Cited by 28 publications

(18 citation statements)

References 19 publications

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“…The UA-lowering drugs that are used to prevent of attacks of gout include xanthine oxidase inhibitors, URAT1 inhibitors, and uricosuric drugs. The xanthine oxidase inhibitors (such as febuxostat) and URAT1 inhibitors (such as lesinurad, pegloticase and allopurinol, AL) inhibit UA production (Jordan et al 2007), while uricosuric drugs (such as probenecid) (Mason 1954) increase the excretion of uric acid in urine. However serious side-effects limit the use of these drugs (Rizzuto et al 1965;Bohm et al 2016;Chung et al 2016;Guttmann et al 2017;Sanchez-Nino et al 2017) and therefore, the development of a comprehensive and safe alternative medication for managing both the acute attack of gout as well as the hyperuricemia is still needed.…”

Section: Introductionmentioning

confidence: 99%

“…The xanthine oxidase inhibitors (such as febuxostat) and URAT1 inhibitors (such as lesinurad, pegloticase and allopurinol, AL) inhibit UA production (Jordan et al. 2007 ), while uricosuric drugs (such as probenecid) (Mason 1954 ) increase the excretion of uric acid in urine. However serious side-effects limit the use of these drugs (Rizzuto et al.…”

Section: Introductionmentioning

confidence: 99%

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N -Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

Wang

et al. 2019

Pharmaceutical Biology

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Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion. Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia. Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 lg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n ¼ 10/ group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6-8 in the model. Results: In the gouty arthritis rat model, BHA at a higher dosage (50 lg) demonstrated a strong antiinflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1b, IL-8, IFN-c, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 lg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%. Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N -Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

Wang

et al. 2019

Pharmaceutical Biology

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“…Probenecid was introduced in 1950 as “Benemid” and suggested as an adjunct to chemotherapy [ 61 ]. It was later used to study the effects of uric acid secretion and associated changes of blood levels in gout patients [ 62 ]. Furthermore, Verapamil was used to improve angina pectoris pain [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Reporter Dyes Demonstrate Functional Expression of Multidrug Resistance Proteins in the Marine Flatworm Macrostomum lignano: The Sponge-Derived Dye Ageladine A Is Not a Substrate of These Transporters

et al. 2013

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The marine plathyhelminth Macrostomum lignano was recently isolated from Adriatic shore sediments where it experiences a wide variety of environmental challenges, ranging from hypoxia and reoxygenation, feeding on toxic algae, to exposure to anthropogenic contaminants. As multidrug resistance transporters constitute the first line of defense against toxins and toxicants we have studied the presence of such transporters in M. lignano in living animals by applying optical methods and pharmacological inhibitors that had been developed for mammalian cells. Application of the MDR1 inhibitor Verapamil or of the MRP1 inhibitors MK571 or Probenecid increased the intracellular fluorescence of the reporter dyes Fura-2 am, Calcein am, Fluo-3 am in the worms, but did not affect their staining with the dyes Rhodamine B, CMFDA or Ageladine A. The marine sponge alkaloid Ageladine A remained intracellularly trapped for several days in the worms, suggesting that it does not serve as substrate of multidrug resistance exporters. In addition, Ageladine A did not affect multidrug resistance-associated protein (MRP)-mediated dye export from M. lignano or the MRP1-mediated glutathione (GSH) export from cultured rat brain astrocytes. The data obtained demonstrate that life-imaging is a useful tool to address physiological drug export from intact marine transparent flatworms by using multiphoton scanning microscopy.

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“…Probenecid can be started by 250 mg twice daily for 1 week and may increase to a maximum of 2 g/day. Moreover, Probenecid is avoided use in patients with eGFR <30 mL/min ( 20 , 21 ). Sulfinpyrazone is started at a dose of 50 mg twice daily, with increments over several weeks to 100 to 200 mg three or four times daily as needed.…”

Section: Introductionmentioning

confidence: 99%

Association Between Use of Anti-gout Preparations and Dementia: Nested Case–Control Nationwide Population-Based Cohort Study

et al. 2021

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Objectives: Gout is the most common form of inflammatory arthritis and was found to be independently associated with incident dementia in the elderly. However, the associations between anti-gout preparations and dementia were not well-studied.Methods: Data were collected from Taiwan's National Health Insurance Research Database (NHIRD). A 2005–2013 retrospective cohort study was conducted, and all investigated subjects were identified by International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Clinical Modification. Conditional logistic regression was used to evaluate the odds ratio of dementia in relation to different gout preparations (benzbromarone, allopurinol, sulfinpyrazone, probenecid) and number of days of anti-gout preparation use, after adjustment for potential confounding variables.Results: A total of 3,242 gout patients with and without dementia were selected from the NHIRD and included in the final analysis after 1:1 matching for age, gender, and diagnosis year of gout. In the anti-gout preparations, only use of Benzbromarone decreased the risk of dementia (adjusted OR, 0.81; 95% CI, 0.68–0.97). The result of the subgroup analysis revealed a trend toward a lower risk of dementia with longer use of benzbromarone. Use of benzbromarone for ≥180 days showed a significantly lower risk of dementia (adjusted OR, 0.72; 95% CI, 0.58–0.89). Moreover, the protective effect was more pronounced in males compared with females.Conclusion: This cohort study reveals that gout patients taking benzbromarone are at a decreased risk of developing incident dementia, especially with longer use and in male. Further prospective trials are warranted to confirm our findings.

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Studies on the Effect of Probenecid (`Benemid') in Gout

Cited by 28 publications

References 19 publications

N -Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

N -Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

Reporter Dyes Demonstrate Functional Expression of Multidrug Resistance Proteins in the Marine Flatworm Macrostomum lignano: The Sponge-Derived Dye Ageladine A Is Not a Substrate of These Transporters

Association Between Use of Anti-gout Preparations and Dementia: Nested Case–Control Nationwide Population-Based Cohort Study

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