| Effects of allopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal hypoxia-ischemia. | |
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MedLine Citation:
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PMID: 12815112 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hypothesis was tested that treatment with allopurinol, a xanthine oxidase inhibitor, or deferoxamine, a chelator of nonprotein-bound iron, preserved cerebral energy metabolism, attenuated development of edema, and improved histologic outcome in the newborn piglet at 24 h after hypoxia-ischemia. Thirty-two newborn piglets were subjected to 1 h of hypoxia-ischemia by occluding both carotid arteries and reducing the fraction of inspired oxygen; five newborn piglets served as sham-operated controls. The depth of hypoxia-ischemia was controlled by phosphorous magnetic resonance spectroscopy. Upon reperfusion and reoxygenation, piglets received vehicle (n= 12), allopurinol (30 mg/kg/d, n = 10), or deferoxamine (12.5 mg/kg/d, n = 10). The cerebral energy status was determined with phosphorous magnetic resonance spectroscopy. The presence of vasogenic edema was assessed by T2-weighted magnetic resonance imaging. Brain cell injury was assessed with caspase-3 activity, histology, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end (TUNEL)-labeling. At 24 h after hypoxia-ischemia, the phosphocreatine/inorganic phosphate ratios were significantly decreased in vehicle-treated, but not in allopurinol- or deferoxamine-treated piglets. Water T2 values were significantly increased at 24 h after hypoxia-ischemia in cerebral cortex, thalamus, and striatum of vehicle-treated piglets, but not in allopurinol- and deferoxamine-treated piglets. No differences in caspase-3 activity, histologic outcome, or TUNEL-labeling were demonstrated between the three treatment groups. We suggest that allopurinol and deferoxamine may have an additional value in the treatment of perinatal hypoxia-ischemia with other neuroprotective agents or in combination with hypothermia. |
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Authors:
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Cacha Peeters-Scholte; Kees Braun; Johanna Koster; Nicole Kops; Klas Blomgren; Giuseppe Buonocore; Sylvia van Buul-Offers; Henrik Hagberg; Klaas Nicolay; Frank van Bel; Floris Groenendaal |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-06-18 |
Journal Detail:
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Title: Pediatric research Volume: 54 ISSN: 0031-3998 ISO Abbreviation: Pediatr. Res. Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-09-29 Completed Date: 2004-07-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 516-22 Citation Subset: IM |
Affiliation:
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Department of Neonatology, Image Sciences Institute, University Medical Center, 3584 EA Utrecht, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Allopurinol
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metabolism,
pharmacology* Animals Animals, Newborn Brain / drug effects*, metabolism, pathology Caspase 3 Caspases / metabolism Deferoxamine / metabolism, pharmacology* Enzyme Inhibitors / metabolism, pharmacology* Hypoxia-Ischemia, Brain / pathology* In Situ Nick-End Labeling Iron / metabolism Iron Chelating Agents / metabolism, pharmacology* Magnetic Resonance Imaging Reperfusion Injury / pathology* Swine |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Iron Chelating Agents; 315-30-0/Allopurinol; 70-51-9/Deferoxamine; 7439-89-6/Iron; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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