Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome.
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.
Sánchez-Lozada
Laura G
LG
Dept. of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Juan Badiano 1, 14080 Mexico City, Mexico. lgsanchezlozada@gmail.com
Tapia
Edilia
E
Bautista-García
Pablo
P
Soto
Virgilia
V
Avila-Casado
Carmen
C
Vega-Campos
Iliana P
IP
Nakagawa
Takahiko
T
Zhao
Lin
L
Franco
Martha
M
Johnson
Richard J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002149:Energy Intake; D000069465:Febuxostat; D005632:Fructose; D006074:Gout Suppressants / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D005632:Fructose; D014969:Xanthine Oxidase