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Differences in Uricogenic Effects of Dietary Purine Bases, Nucleosides and Nucleotides in Rats

Danielle Brulé^*,, Ghulam Sarwar^*,1, Laurent Savoie, James Campbell and Murray van Zeggelaar^*,

^* Bureau of Nutritional Sciences Bureau of Chemical Safety, Food Directorate, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario, Canada K1A OL2 Centre de Recherche en Nutrition, Université Laval, Ste-Foy, Québec, Canada G1K 7P4 Animal and Poultry Science Department, University of Guelph, Guelph, Ontario, Canada N1G 2W1

The uricogenic effects of dietary free purines (adenine, guanine, hypoxanthine and xanthine), their nucleosides (adenosine, guanosine and inosine) and nucleotides (adenosine monophosphate, guanosine monophosphate and inosine monophosphate) were studied in rats. Casein-based diets (20% protein) supplemented with 30 mmol/kg diet of each of the free purine base, nucleoside or nucleotide were fed to male Sprague-Dawley rats (100 ± 5 g) for 14 d. Addition of adenine resulted in less weight gain than in controls, greater kidney weight, greater urine volume and higher levels of blood urea nitrogen, serum uric acid, creatinine and allantoin but lower urinary levels of allantoin, uric acid and creatinine. The adenine diet also caused nephropathy characterized by nephromegaly and deposition of crystals. A microscopic examination of the kidneys revealed deposition of crystals mainly in the lumen of convoluted tubules of the cortex. Feeding of diets containing other purine bases, nucleosides and nucleotides had no adverse effects on kidney weight or structure, urine volume, serum uric acid or creatinine. Urinary allantoin excretion, however, was greater in rats fed hypoxanthine, xanthine, nucleoside and nucleotide diets than in control rats. Adenine produced adverse effects only when fed in the free form and not when fed as the nucleoside or nucleotide, suggesting a metabolic significance for free adenine in predicting hyperuricemic effects of foods.

KEY WORDS: • dietary purines • nucleosides • nucleotides • uric acid • allantoin • kidney histopathology • rat

¹ To whom correspondence and reprint requests should be addressed.

Manuscript received 30 November 1987. Revision accepted 3 February 1988.