Synergistic effect of uricase blockade plus physiological amounts of fructose-glucose on glomerular hypertension and oxidative stress in rats.

Abstract

Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders, and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n = 7/group) were studied during 8 wk: water + vehicle (V), water + oxonic acid (OA; 750 mg/k BW), sweetened beverage (SB; 11% fructose-glucose combination) + V, and SB + OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase, and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia, and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension, and SB alone induced insulin resistance. SB + OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic TG, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose.

• Authors: Edilia Tapia, Magdalena Cristóbal, Fernando E García-Arroyo, Virgilia Soto, Fabiola Monroy-Sánchez, Ursino Pacheco, Miguel A Lanaspa, Carlos A Roncal-Jiménez, David Cruz-Robles, Takuji Ishimoto, Magdalena Madero, Richard J Johnson, Laura-Gabriela Sánchez-Lozada
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 304 Issue 6 Pg. F727-36 (Mar 15 2013) ISSN: 1522-1466 [Electronic] United States
• PMID: 23303409 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Uric Acid
• Fructose
• Oxonic Acid
• Urate Oxidase
• Fructokinases
• ketohexokinase
• Glucose

Topics

• Animals
• Beverages (adverse effects)
• Fatty Liver (etiology)
• Fructokinases (metabolism)
• Fructose (adverse effects)
• Glucose (adverse effects)
• Hypertrophy (etiology)
• Hyperuricemia (chemically induced)
• Insulin Resistance
• Kidney (drug effects, pathology)
• Kidney Diseases (enzymology, etiology, pathology)
• Liver (drug effects, metabolism)
• Male
• Metabolic Syndrome (etiology)
• Oxidative Stress (drug effects)
• Oxonic Acid
• Rats
• Rats, Sprague-Dawley
• Renal Circulation (drug effects)
• Urate Oxidase (antagonists & inhibitors, metabolism)
• Uric Acid (metabolism)
• Vasoconstriction (drug effects)