Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several experimental models on adult and newborn animals showed that in cerebral hypoxic-ischemic conditions similar to clinical states the main source of the excessive production of free oxygen radicals is the highly activated xanthine oxidase (XO) enzyme reaction. Long before this data were available, it became known that the main role of allopurinol (AP) is the inhibition of XO. On the basis of these results, many therapeutic trials with AP were performed both in experimental and clinical studies of ischemia and reperfusion. However, it has been shown that only preventive administration of AP has favorable effects. The explanation for the poor results of AP treatment in human fetal brain damage (FBD) cases is that the drug was applied postnatally. The clinical studies performed in healthy laboring mothers whose deliveries were complicated with FBD showed that placental transfer after prenatal administration of AP may be effective in protecting newborns at increased risk of hypoxic-ischemic cerebral damage. Further controlled trials are required to determine if the prophylactic use of the drug might prevent hypoxic-ischemic injuries when the drug is administered immediately prior to impending fetal hypoxia, or even in deliveries at risk of developing hypoxia.
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PMID:Results of and further prevention of hypoxic fetal brain damage by inhibition of xanthine oxidase enzyme with allopurinol. 2141 Apr 9

Hypoxia is a common challenge to the fetus, promoting a physiological defence to redistribute blood flow towards the brain and away from peripheral circulations. During acute hypoxia, reactive oxygen species (ROS) interact with nitric oxide (NO) to provide an oxidant tone. This contributes to the mechanisms redistributing the fetal cardiac output, although the source of ROS is unknown. Here, we investigated whether ROS derived from xanthine oxidase (XO) contribute to the fetal peripheral vasoconstrictor response to hypoxia via interaction with NO-dependent mechanisms. Pregnant ewes and their fetuses were surgically prepared for long-term recording at 118 days of gestation (term approximately 145 days). After 5 days of recovery, mothers were infused i.v. for 30 min with either vehicle (n = 11), low dose (30 mg kg(-1), n = 5) or high dose (150 mg kg(-1), n = 9) allopurinol, or high dose allopurinol with fetal NO blockade (n = 6). Following allopurinol treatment, fetal hypoxia was induced by reducing maternal inspired O2 such that fetal basal P aO 2 decreased approximately by 50% for 30 min. Allopurinol inhibited the increase in fetal plasma uric acid and suppressed the fetal femoral vasoconstrictor, glycaemic and lactate acidaemic responses during hypoxia (all P < 0.05), effects that were restored to control levels with fetal NO blockade. The data provide evidence for the activation of fetal XO in vivo during hypoxia and for XO-derived ROS in contributing to the fetal peripheral vasoconstriction, part of the fetal defence to hypoxia. The data are of significance to the understanding of the physiological control of the fetal cardiovascular system during hypoxic stress. The findings are also of clinical relevance in the context of obstetric trials in which allopurinol is being administered to pregnant women when the fetus shows signs of hypoxic distress.
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PMID:Xanthine oxidase and the fetal cardiovascular defence to hypoxia in late gestation ovine pregnancy. 2448 71