Effect of fructose administration on serum urate levels in the uricase inhibited rat

Stavrić, B.; Johnson, Willard J.; Clayman, S.; Gadd, R. E. A.; Chartrand, A.

doi:10.1007/bf01940847

Cited by 32 publications

(22 citation statements)

References 9 publications

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“…After withdrawal of the diet, XOR-I may have inhibited renal XOR with a subsequent progression of renal damage. uric acid to allantoin, and, therefore, hyperuricemia rarely occurs (38). Renal toxicity in adenine-induced nephropathy, therefore, is induced by 2,8-dihydroxyadenine (DHA) (18), a metabolic product of adenine catalyzed by XOR (Fig.…”

Section: Discussionmentioning

confidence: 99%

Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury

Kamijo‐Ikemori

Sugaya

Hibi³

et al. 2016

American Journal of Physiology-Renal Physiology

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The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.

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Section: Discussionmentioning

confidence: 99%

Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury

Kamijo‐Ikemori

Sugaya

Hibi³

et al. 2016

American Journal of Physiology-Renal Physiology

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“…This latter finding is all the more relevant since humans lack uricase and hence develop hyperuricemia more readily than rodents in response to diet (16). Indeed, the administration of small doses of an uricase inhibitor to rats fed fructose dramatically increases the serum UA (34). Thus, while large doses (Ͼ60% caloric intake) of fructose were needed to observe the renal hemodynamic effects in these rats, it is likely that lower doses would be necessary in humans.…”

Section: Discussionmentioning

confidence: 99%

Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats

Sánchez‐Lozada

Tapia

Jiménez

et al. 2007

American Journal of Physiology-Renal Physiology

298

205

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Sá nchez-Lozada LG, Tapia E, Jiménez A, Bautista P, Cristó bal M, Nepomuceno T, Soto V, Á vila-Casado C, Nakagawa T, Johnson RJ, Herrera-Acosta J, Franco M. Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats. Am J Physiol Renal Physiol 292: F423-F429, 2007. First published August 29, 2006; doi:10.1152/ajprenal.00124.2006.-Fructose intake has been recently linked to the epidemic of metabolic syndrome and, in turn, the metabolic syndrome has been epidemiologically linked with renal progression. The renal hemodynamic effects of fructose intake are unknown, as well as the effects of different routes of administration. Metabolic syndrome was induced in rats over 8 wk by either a high-fructose diet (60%, F60, n ϭ 7) or by adding fructose to drinking water (10%, F10, n ϭ 7). Body weight and food and fluid intake of each rat were measured weekly during the follow-up. At baseline and at the end of wk 8, systolic blood pressure, plasma uric acid, and triglycerides were measured. At the end of week 8 glomerular hemodynamics was evaluated by micropuncture techniques. Wall thickening in outer cortical and juxtamedullary afferent arterioles was assessed by immunohistochemistry and computer image analysis. Fructose administration either in diet or drinking water induced hypertension, hyperuricemia, and hypertriglyceridemia; however, there was a progressive increment in these parameters with higher fructose intake (CϽF10ϽF60). In addition, the F60 rats developed kidney hypertrophy, glomerular hypertension, cortical vasoconstriction, and arteriolopathy of preglomerular vessels. In conclusion, fructoseinduced metabolic syndrome is associated with renal disturbances characterized by renal hypertrophy, arteriolopathy, glomerular hypertension, and cortical vasoconstriction. These changes are best observed in rats administered high doses (60% diet) of fructose. uric acid; obesity METABOLIC SYNDROME IS A PATHOPHYSIOLOGICAL entity characterized by insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and obesity (27). The risk for developing diabetes type 2, cardiovascular disease, and renal disease is increased with increasing manifestations of the various components of the syndrome within any individual.The macronutrient content of the diet has been linked to the metabolic syndrome. Recently, consumption of dietary fructose has been suggested to be one of the environmental factors contributing to the development of obesity and the accompanying abnormalities of the metabolic syndrome (7). In fact, a well-known experimental model of metabolic syndrome is induced by high consumption of fructose; this model induces hypertension, hypertriglyceridemia, hyperinsulinemia, and insulin resistance in rats (12). Fructose consumption is able to produce these effects because fructose is more lipogenic than glucose and usually causes greater elevations of triglycerides (10), which, in turn, increases intramyocellular triglyceride content in the skeletal muscle, causing...

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“…High concentrations of fructose (60%) can induce hyperuricemia in rats, which has been shown to have a causal role in the development of metabolic syndrome in rat 6 ; however, the effect of fructose to cause hyperuricemia in rats is markedly increased when uricase is inhibited. 28 Furthermore, rats given 20% fructose and a uricase inhibitor develop hypertension and hyperinsulinemia after several weeks. 29 In conclusion, we present the first evidence that fructose, at concentrations achieved in the current American diet, can induce inflammatory changes in human vascular cells.…”

Section: Discussionmentioning

confidence: 99%

Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells

Glushakova

Kosugi

Roncal

et al. 2008

Journal of the American Society of Nephrology

143

113

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Epidemiologic studies have linked fructose intake with the metabolic syndrome, and it was recently reported that fructose induces an inflammatory response in the rat kidney. Here, we examined whether fructose directly stimulates endothelial inflammatory processes by upregulating the inflammatory molecule intercellular adhesion molecule-1 (ICAM-1). When human aortic endothelial cells were stimulated with physiologic concentrations of fructose, ICAM-1 mRNA and protein expression increased in a time-and dosage-dependent manner, which was independent of NF-B activation. Fructose reduced endothelial nitric oxide (NO) levels and caused a transient reduction in endothelial NO synthase expression. The administration of an NO donor inhibited fructose-induced ICAM-1 expression, whereas blocking NO synthase enhanced it, suggesting that NO inhibits endothelial ICAM-1 expression. Furthermore, fructose resulted in decreased intracellular ATP; administration of exogenous ATP blocked fructose-induced ICAM-1 expression and increased NO levels. Consistent with the in vitro studies, dietary intake of fructose at physiologic dosages increased both serum ICAM-1 concentration and endothelial ICAM-1 expression in the rat kidney. These data suggest that fructose induces inflammatory changes in vascular cells at physiologic concentrations.

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Effect of fructose administration on serum urate levels in the uricase inhibited rat

Cited by 32 publications

References 9 publications

Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury

Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury

Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats

Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells

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