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

Based on accumulating evidence of the role of xanthine oxidase (XO) in generating oxygen free radicals and causing tissue damage during ischemia, we examined the possible role of XO in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). After inducing SAH in dogs by two autologous blood injections 2 days apart, chronic vasospasm of the basilar artery was reliably produced. There was a 3.5-fold elevation in uric acid (UA), the product of XO, in the cerebrospinal fluid (CSF) of these animals. Parenteral administration of allopurinol (i.v., 25 mg/kg, every 6 hours), a specific blocker of XO, successfully abolished the elevation in CSF uric acid levels due to SAH. However, angiographic vasospasm measured on Day 7, morphological changes observed by electron microscope, and elevated CSF prostaglandin levels were not altered by the treatment. It can be concluded that the observed activation of the enzyme XO, which is a well-known source of oxygen free radicals in ischemia in various organs, is not playing a major role in the pathogenesis of chronic cerebral vasospasm in this animal.
 ...
PMID:Production of uric acid in cerebrospinal fluid after subarachnoid hemorrhage in dogs: investigation of the possible role of xanthine oxidase in chronic vasospasm. 361 2

Aneurismal subarachnoid haemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. The mortality is approximately 50%, with 30% of survivors having significant morbidity. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury and cerebral vasospasm following SAH. There are several sources for the excessive generation of free radicals following SAH, including disrupted mitochondrial respiration and extracellular hemoglobin. There is also the upregulation of free radical producing enzymes such as inducible nitric oxide synthase (iNOS), xanthine oxidase, NADPH oxidase (NOX), as well as enzymes involved in the metabolism of arachidonic acid. Additionally, intrinsic antioxidant systems such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are inhibited. Experiments have linked free radicals to the apoptosis of neurons and endothelial cells, BBB breakdown and the altered contractile response of cerebral vessels following SAH. Antioxidant therapy has provided neuroprotection and antispasmotic effects in experimental SAH and some therapies have demonstrated improved outcomes in clinical trials. These studies have laid a foundation for the use of antioxidants in the treatment of aneurismal SAH.
 ...
PMID:Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. 1845 95