Effects of allopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal hypoxia-ischemia

Pediatr Res. 2003 Oct;54(4):516-22. doi: 10.1203/01.PDR.0000081297.53793.C6. Epub 2003 Jun 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / metabolism
  • Allopurinol / pharmacology*
  • Animals
  • Animals, Newborn
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Caspase 3
  • Caspases / metabolism
  • Deferoxamine / metabolism
  • Deferoxamine / pharmacology*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Hypoxia-Ischemia, Brain / pathology*
  • In Situ Nick-End Labeling
  • Iron / metabolism
  • Iron Chelating Agents / metabolism
  • Iron Chelating Agents / pharmacology*
  • Magnetic Resonance Imaging
  • Reperfusion Injury / pathology*
  • Swine


  • Enzyme Inhibitors
  • Iron Chelating Agents
  • Allopurinol
  • Iron
  • Caspase 3
  • Caspases
  • Deferoxamine