Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome

Abstract

Increased fructose consumption is associated with hyperuricemia, metabolic syndrome, and renal damage. This study evaluated whether febuxostat (Fx), an investigational nonpurine, and selective xanthine oxidase inhibitor, could alleviate the features of metabolic syndrome as well as the renal hemodynamic alterations and afferent arteriolopathy induced by a high-fructose diet in rats. Two groups of rats were fed a high-fructose diet (60% fructose) for 8 wk, and two groups received a normal diet. For each diet, one group was treated with Fx (5-6 mg.kg(-1).day(-1) in the drinking water) during the last 4 wk (i.e., after the onset of metabolic syndrome), and the other received no treatment (placebo; P). Body weight was measured daily. Systolic blood pressure and fasting plasma uric acid (UA), insulin, and triglycerides were measured at baseline and at 4 and 8 wk. Renal hemodynamics and histomorphology were evaluated at the end of the study. A high-fructose diet was associated with hyperuricemia, hypertension, as well as increased plasma triglycerides and insulin. Compared with fructose+P, fructose+Fx rats showed significantly lowered blood pressure, UA, triglycerides, and insulin (P < 0.05 for all comparisons). Moreover, fructose+Fx rats had significantly reduced glomerular pressure, renal vasoconstriction, and afferent arteriolar area relative to fructose+P rats. Fx treatment in rats on a normal diet had no significant effects. In conclusion, normalization of plasma UA with Fx in rats with metabolic syndrome alleviated both metabolic and glomerular hemodynamic and morphological alterations. These results provide further evidence for a pathogenic role of hyperuricemia in fructose-mediated metabolic syndrome.

Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury

“…In that study, the dehydration procedure was severe (34). We have also shown that a 60% fructose diet induces renal damage in the course of 8 wk (36). Moreover, rats that received a similar FG beverage ad libitum developed mild renal damage; however, those animals ingested ϳ80 ml of this fluid per day (39) in contrast to the present study in which rats had a limited consumption of this sweetened beverage (12 ml/day).…”

Regulation of the fructose transporter GLUT5 in health and disease

“…In rodents, fructose, unlike other sugars, induces hyperuricemia (115,132) which is a major risk factor for hypertension (50). Recent clinical studies using patient data from the Third National Health and Nutrition Examination Survey confirm the link not only between hyperuricemia and hypertension in particular but also between serum concentrations of uric acid and the prevalence of metabolic syndrome in general (29,53).…”

Plasma Urate and Risk of a Hospital Stay with AKI

“…In animal studies, lowering urate reduced glomerular hypertension, preserved renal function, and decreased tubulointerstitial fibrosis, supporting a potential causal role of hyperuricemia in kidney disease (35,38). If a causal relationship exists, urate might also be useful in identifying individuals at substantial risk for AKI, particularly AKI that occurs in the setting of hemodynamic instability or tubulointerstitial damage.…”