Response of Purine Metabolism and Cortical Oxygen Pressure to Hypoxia and Reoxygenation in Newborn Piglets

Abstract

It has been proposed that the level of purine metabolites (particularly hypoxanthine) reflects the intracellular energy metabolism and can be used as sensitive, specific markers of response of tissue to hypoxic/ischemic conditions.26,27 Several studies have shown that hypoxic conditions cause breakdown of cellular nucleotides resulting in accumulation of hypoxanthine and xanthine4,7,8,28 and these metabolites can serve as oxidizable purine sub-strates for xanthine dehydrogenase and oxidase. One of the possible mechanisms of tissue damage during reoxygenation following hypoxic/ischemic conditions is through genera-tion of free radicals by the hypoxanthine-xanthine oxidase reactions.1,5,615,16,24,29 Under hy-poxic/ischemic conditions the elevated cytosolic calcium concentration can activate a protease, calpain, which converts xanthine dehydrogenase to xanthine oxidase.32 During posthypoxic reoxygenation xanthine oxidase catalyzes oxidation of xanthine to uric acid with formation of Superoxide radical O2 4,15,28. The Superoxide radical can further react with hydrogen peroxide produced in the same reaction and form hydroxyl radicals. Contribution of toxic oxygen metabolites from xanthine oxidase to tissue injury during reoxy-genation has been based particularly on studies showing that the inhibitors of xanthine oxidase, such as allopurinol, decrease the postischemic injury of different tissues.9,19,20,21,24 KeywordsUric AcidHypoxic ConditionXanthine OxidasePurine MetabolismNewborn PigletThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.