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.
Shadid
M
M
Department of Pediatrics, Leiden University Medical Centre, The Netherlands.
Buonocore
G
G
Groenendaal
F
F
Moison
R
R
Ferrali
M
M
Berger
H M
HM
van Bel
F
F
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