Therapeutic targets for gout

Sorbera, L. A.; Sharanya, S.; Dulsat, C.; Rosa, Eduardo Augusto Silva

doi:10.1358/dof.2010.035.04.1502253

Cited by 5 publications

(6 citation statements)

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“…Between 1 and 2% of the population in industrial countries suffers from gout, a painful result of hyperuricemia [Burns and Wortmann, 2011;Eggebeen, 2007;Sorbera et al, 2010]. In symptomless intervals between gout attacks, uricostatic or uricosuric agents and in some cases recombinant urate oxidase are given to reduce the uric acid content of serum [Eggebeen, 2007;Jordan, 2012;Leinmüller, 2001;Schlesinger et al, 2011;Tausche et al, 2009;Terkeltaub, 2010;Wittköpper et al, 2011].…”

Section: Discussionmentioning

confidence: 99%

“…A minority of patients with hyperuricemia develop microscopic and macroscopic monosodium urate crystals, which cause swelling, inflammation and/or pain in joints and results in painful gout attacks [Sorbera et al, 2010;Terkeltaub, 2010]. Between 1 and 2% of the population in industrial countries are affected by this disease [Burns and Wortmann, 2011;Eggebeen, 2007;Sorbera et al, 2010].…”

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confidence: 99%

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Arxula adeninivorans Recombinant Guanine Deaminase and Its Application in the Production of Food with Low Purine Content

Trautwein-Schult

Jankowska²,

Cordes³

et al. 2014

Microb Physiol

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Purines of exogenous and endogenous sources are degraded to uric acid in human beings. Concentrations >6.8 mg uric acid/dl serum cause hyperuricemia and its symptoms. Pharmaceuticals and the reduction of the intake of purine-rich food are used to control uric acid levels. A novel approach to the latter proposition is the enzymatic reduction of the purine content of food by purine-degrading enzymes. Here we describe the production of recombinant guanine deaminase by the yeast Arxula adeninivorans LS3 and its application in food. In media supplemented with nitrogen sources hypoxanthine or adenine, guanine deaminase (AGDA) gene expression is induced and intracellular accumulation of guanine deaminase (Agdap) protein occurs. The characteristics of the guanine deaminase isolated from wild-type strain LS3 and a transgenic strain expressing the AGDA gene under control of the strong constitutive TEF1 promoter were determined and compared. Both enzymes were dimeric and had temperature optima of 55°C with high substrate specificity for guanine and localisation in both the cytoplasm and vacuole of yeast. The enzyme was demonstrated to reduce levels of guanine in food. A mixture of guanine deaminase and other purine degradation enzymes will allow the reduction of purines in purine-rich foods.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Arxula adeninivorans Recombinant Guanine Deaminase and Its Application in the Production of Food with Low Purine Content

Trautwein-Schult

Jankowska²,

Cordes³

et al. 2014

Microb Physiol

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“…Hyperuricemia, and its symptoms, gout, tophi and acute uric acid nephropathy, is widespread in industrial countries (1-2% of adults) [Sorbera et al, 2010]. Reduced renal uric acid excretion and increased uric acid synthesis result in increased serum uric acid concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…A minority of patients with hyperuricemia develop symptoms of gout, tophi and acute uric acid nephropathy [Wortmann, 2002], which are caused by the formation of micro-and macroscopic monosodium urate crystals. These crystals cause swelling, inflammation and pain in the joints of the lower extremities [Sorbera et al, 2010] and worldwide, between 1 and 2% of adults, mostly male, and often in industrialized countries, are affected by gout [Sorbera et al, 2010].…”

Section: Introductionmentioning

confidence: 99%

“…In the case of acute gout attacks, patients are often treated with nonsteroidal anti-inflammatory drugs and glucocorticoids for reduction of pain and treatment of inflammation [Sorbera et al, 2010] or recombinant urate oxidase-like rasburicase (Fasturtec ® ; Sanofi-Aventis) [Leinmüller, 2001] or pegloticase (Krystexxa ® ; Savient Pharmaceuticals) [Schlesinger et al, 2011] to rapidly reduce uric acid levels by converting it to allantoin which is 5-10 times more soluble. Common prophylaxis and long-term therapies are made with the xanthine oxidase inhibitors allopurinol and febuxostat or uricosuric agents such as probenecid or benzbromarone [Burns and Wortmann, 2011;Wittköpper et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

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Arxula adeninivorans Recombinant Urate Oxidase and Its Application in the Production of Food with Low Uric Acid Content

Trautwein-Schult

Jankowska

Cordes³

et al. 2013

Microb Physiol

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Hyperuricemia and its symptoms are becoming increasingly common worldwide. Elevated serum uric acid levels are caused by increased uric acid synthesis from food constituents and reduced renal excretion. Treatment in most cases involves reducing alcohol intake and consumption of meat and fish or treatment with pharmaceuticals. Another approach could be to reduce uric acid level in food, either during production or consumption. This work reports the production of recombinant urate oxidase by Arxula adeninivorans and its application to reduce uric acid in a food product. The A. adeninivorans urate oxidase amino acid sequence was found to be similar to urate oxidases from other fungi (61-65% identity). In media supplemented with adenine, hypoxanthine or uric acid, induction of the urate oxidase (AUOX) gene and intracellular accumulation of urate oxidase (Auoxp) was observed. The enzyme characteristics were analyzed from isolates of the wild-type strain A. adeninivorans LS3, as well as from those of transgenic strains expressing the AUOX gene under control of the strong constitutive TEF1 promoter or the inducible AYNI1 promoter. The enzyme showed high substrate specificity for uric acid, a broad temperature and pH range, high thermostability and the ability to reduce uric acid content in food.

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Anti-Hyperuricemic and Nephroprotective Effects of Rhein in Hyperuricemic Mice

et al. 2015

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Hyperuricemia has been considered to be a key risk factor for kidney disease. The formation of uric acid crystals in the kidney further stimulates an intensive inflammatory response. Rhein possesses various pharmacological activities, including anti-inflammatory, antioxidative, antitumor, purgative effects, and so on. To our knowledge, no previous work has been reported about the therapeutic effect of rhein on urate nephropathy. In this study, a model of hyperuricemia and nephropathy induced by adenine and ethambutol in mice was established. Meanwhile, the potential beneficial effects and mechanisms of rhein on hyperuricemia and nephropathy were also investigated. The results demonstrated that rhein significantly decreased the serum uric acid level by inhibiting the xanthine oxidase activity and increasing the excretion of urinary uric acid. In addition, rhein also markedly improved kidney damage related to hyperuricemia. Further investigation indicated that rhein improved the symptoms of nephropathy through decreasing the production of proinflammatory cytokines, including interleukin 1β, prostaglandin E2, and tumor necrosis factor-α and inhibiting the expression of transforming growth factor-β1. The present study suggests that rhein may have a considerable potential for development as an anti-hyperuricemic and nephroprotective agent for clinical application.

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Therapeutic targets for gout

Cited by 5 publications

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<b><i>Arxula adeninivorans</i></b> Recombinant Guanine Deaminase and Its Application in the Production of Food with Low Purine Content

<b><i>Arxula adeninivorans</i></b> Recombinant Guanine Deaminase and Its Application in the Production of Food with Low Purine Content

<b><i>Arxula adeninivorans</i></b> Recombinant Urate Oxidase and Its Application in the Production of Food with Low Uric Acid Content

Anti-Hyperuricemic and Nephroprotective Effects of Rhein in Hyperuricemic Mice

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