Effect of deferoxamine and allopurinol on non-protein-bound iron concentrations in plasma and cortical brain tissue of newborn lambs following hypoxia-ischemia.
Reduction of non-protein-bound iron (NPBI) using iron chelators may attenuate hypoxia-ischemia-induced reperfusion injury of the brain. This study investigated whether administration of low-dose deferoxamine and allopurinol, both having NPBI-chelating properties, reduced hypoxia-ischemia-induced NPBI formation in plasma effluent from the brain and in cerebral cortical tissue. Twenty-one newborn lambs underwent severe hypoxia-ischemia. Upon reperfusion and reoxygenation the lambs received either a placebo (n = 7), or deferoxamine 2.5 mg/kg (n = 7) or allopurinol 20 mg/kg (n = 7). The post-hypoxic-ischemic NPBI levels in plasma were significantly lower after deferoxamine but not after allopurinol as compared to placebo-treated lambs. Cortical NPBI levels in both deferoxamine and allopurinol-treated lambs were significantly lower than NPBI levels in placebo-treated lambs. We conclude that deferoxamine effectively lowers NPBI in plasma effluent from the brain, and that both, deferoxamine and allopurinol, lower NPBI in cortical brain tissue.
Department of Pediatrics, Leiden University Medical Centre, The Netherlands.
M
M
Shadid
G
G
Buonocore
F
F
Groenendaal
R
R
Moison
M
M
Ferrali
H M
HM
Berger
F
F
van Bel
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000378:metabolism*; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012756:Sheep
D007502:Iron Chelating Agents; D009419:Nerve Tissue Proteins; D000493:Allopurinol; D007501:Iron; D003676:Deferoxamine