Effects of Dietary Protein, Adenine, and Allopurinol on Growth and Metabolism of Rats

Abstract

The effects of dietary protein level, 4-hydroxypyrazolo-(3,4-d)pyrimidine (allopurinol), and adenine on kidney morphology, histology, and intracellular localization of adenine metabolites in rats are described. Rats fed semipurified diets containing 20% and 5% casein supplemented with 0.4% adenine alone, and in combination with 0.033% allopurinol, had a smaller growth rate, a greater urine volume, larger kidneys and greater plasma urea nitrogen concentration compared with rats fed the control and the allopurinol supplemented diets. The level of dietary protein and the presence of allopurinol in the diet did not affect kidney weight, urine volume or plasma urea nitrogen concentration. Approximately 4% of the dietary adenine consumed was recovered as 2,8-dioxyadenine in the kidneys which were enlarged and pallid with extensive crystalline occlusions in the cortical tubules, localized areas of inflammatory response, and a sloughing of the tubular epithelial lining. Kidney cells from adenine-fed rats were devoid of structural integrity and had accumulations of electron dense material within the mitochondria. Removal of adenine from the diet reversed the adverse effects of adenine on growth rate, kidney weight and plasma urea nitrogen levels, but did not reverse the changes in urine volume. These studies show that the metabolic effects of dietary adenine were independent of dietary protein and allopurinol and, with the exception of urine volume, the metabolic effects were reversed when adenine was removed from the diet.