Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies the signs associated with copper deficiency in rats fed fructose.
This study was designed to focus on the potential stress that xanthine oxidase could produce in copper-deficient rats fed fructose. Fructose consumption results in an excess production of uric acid due to an increased degradation of nucleotides. The enzyme xanthine oxidase catalyzes the oxidation of both hypoxanthine and xanthine. During the oxidation process free radicals are generated, which in turn, induce lipid peroxidation and premature death. Allopurinol -- a competitive inhibitor of xanthine oxidase -- could alleviate the combined effects of fructose feeding and copper deficiency. Twenty-five male rats were fed for 4 weeks from weaning a copper-deficient or adequate diet containing fructose. Twelve rats were given a daily oral dose of 5 mg allopurinol/100 g b.wt. Two copper-deficient rats that were not treated with allopurinol died prematurely during the fourth week of the study. No mortality occurred in the group of copper-deficient rats that had been treated with allopurinol. Anemia was alleviated by allopurinol, which in turn, could be responsible for improved growth rate. Allopurinol was effective in inhibiting xanthine oxidase activity in vivo as measured by the dramatic reduction of uric acid production. Lipid peroxidation, however, was not affected by allopurinol. It is concluded that the beneficial effects of allopurinol in copper deficiency do not appear to be related to prevention of oxygen radicals, but rather, to the protection against the catabolic destruction of purines, which in turn, increases nucleotide pool.
Laboratory of Metabolism and Nutrient Interactions, USDA, ARS, Beltsville Human Nutrition Research Center, MD, USA.
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D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D003300:Copper / Q000172:deficiency*; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005609:Free Radicals; D005632:Fructose / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005609:Free Radicals; D014527:Uric Acid; D005632:Fructose; D000493:Allopurinol; D003300:Copper; D014969:Xanthine Oxidase