Fields M, Lewis C G, Lure M D
Laboratory of Metabolism and Nutrient Interactions, USDA, ARS, Beltsville Human Nutrition Research Center, MD, USA.
Free Radic Biol Med. 1996;20(4):595-600. doi: 10.1016/0891-5849(95)02056-x.
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.
本研究旨在关注黄嘌呤氧化酶在喂食果糖的缺铜大鼠中可能产生的潜在应激。由于核苷酸降解增加,摄入果糖会导致尿酸过量产生。黄嘌呤氧化酶催化次黄嘌呤和黄嘌呤的氧化。在氧化过程中会产生自由基,进而诱导脂质过氧化和过早死亡。别嘌呤醇——一种黄嘌呤氧化酶的竞争性抑制剂——可以减轻喂食果糖和缺铜的联合影响。25只雄性大鼠从断奶开始喂食含果糖的缺铜或正常饮食4周。12只大鼠每天口服5毫克别嘌呤醇/100克体重。在研究的第四周,两只未用别嘌呤醇治疗的缺铜大鼠过早死亡。用别嘌呤醇治疗的缺铜大鼠组未出现死亡。别嘌呤醇减轻了贫血,这反过来可能是生长速率提高的原因。通过尿酸产量的显著降低来衡量,别嘌呤醇在体内有效抑制了黄嘌呤氧化酶的活性。然而,脂质过氧化不受别嘌呤醇的影响。得出的结论是,别嘌呤醇在缺铜中的有益作用似乎与预防氧自由基无关,而是与防止嘌呤的分解破坏有关,这反过来又增加了核苷酸池。