Oral uricase eliminates blood uric acid in the hyperuricemic pig model

Abstract

An elevated level of serum uric acid—hyperuricemia, is strongly associated with the development of gout and chronic kidney disease (CKD) which is often accompanied by a significantly reduced glomerular filtration rate (GFR). In the present study, we investigated the extra-renal elimination of uric acid via the intestine in a healthy pig model and the effect of oral uricase therapy on plasma uric acid concentrations in pigs with induced hyperuricemia and CKD. The experiment was conducted on eleven, ten-week-old pigs (n = 11). The porcine model of CKD was developed by performing 9/10 nephrectomy surgery on eight pigs. A stable model of hyperuricemia was established in only five of the eight nephrectomized pigs by frequent injections of uric acid (UA) into the jugular vein. All pigs (three healthy pigs and five CKD pigs) were operated for implantation of jugular vein catheters and the three healthy pigs also had portal vein catheters inserted. Blood uric acid concentrations were measured spectrophotometrically, using the Uric Acid Assay Kit (BioAssay Systems, Hayward, USA). The piglets with CKD received orally administered uricase (treatment) and served as their own controls (without uricase supplementation). Oral uricase therapy significantly decreased plasma uric acid concentrations in pigs with CKD, whereas hyperuricemia was observed in the pigs whilst not being treated with uricase. Urinary uric acid excretion was similar during both the treatment and control periods during the first 8 h and 24 h after UA infusions in the CKD pigs. To demonstrate the elimination of UA via the intestine, the healthy pigs were infused with UA into the jugular vein. The blood collected from the jugular vein represents circulating UA concentrations and the blood collected from the portal vein represents the concentration of UA leaving the intestine. The final (after 2 h) concentration of UA was significantly lower in blood collected from the portal vein compared to that collected from the jugular vein (3.34 vs. 2.43 mg/dL, respectively, p = 0.024). The latter allows us to suggest that UA is eliminated from the blood via the gut tissue.

Construction and expression of recombinant uricase‑expressing genetically engineered bacteria and its application in rat model of hyperuricemia

“…The uric acid in the intestine primarily originates from both endogenous (SUA) and exogenous (food) sources. Endogenous uric acid is not only comprised of SUA (46,47), but also a small amount of uric acid secreted from liver (48). The penetration of SUA into the intestine occurs through passive diffusion (49), and may be associated with the organic ion transporter 10 (OAT10) in the intestinal mucosa (50).…”

Uricemia in juvenile pigs model: effect of nephrectomy and potassium oxonate

“…Moreover, these authors showed alterations in intestinal urate transport in rats with chronic renal failure in comparison to that of normal rats. In our previous study we also demonstrated that UA, after reaching a certain plasma urate threshold, can be eliminated via the intestine in pigs (Szczurek et al, 2017). In addition, Simmonds et al (1976) suggested that porcine kidneys handle urate as an organic acid, which can thus be eliminated very effectively by filtration and secretion.…”

“…Therefore, studies of metabolomics and proteomics with this model is a critical step in understanding physiology, pathophysiology and the development of therapies in both humans and animals (Malagrino et al, 2014). In our previous study we investigated the extra-renal elimination of uric acid via the intestine in a healthy pig model and the effect of oral uricase therapy on plasma uric acid concentrations in nephrectomized pigs with induced hyperuricemia (Szczurek et al, 2017). Many studies described development of hyperuricemia in human with chronic kidney disease (CKD) and obesity (de Oliveira and Burini, 2012).…”

Desempenho e características de carcaça de suínos em crescimento alimentados com torta de algodão e complexo enzimático

“…Ele é formado pelo fígado e excretado pelos rins e intestino (So e Thorens, 2010). Na maioria dos mamíferos, entre eles os suínos, ocorre atividade de urato oxidase, por meio da enzima uricase, que auxilia na degradação do ácido úrico (Szczurek et al, 2017). Devido à presença dessa enzima, as concentrações de ácido úrico em suínos são abaixo de 2mg/dL e dependerão do equilíbrio entre síntese e degradação de ácido úrico no organismo.…”