Effect of deferoxamine and allopurinol on non-protein-bound iron concentrations in plasma and cortical brain tissue of newborn lambs following hypoxia-ischemia

Abstract

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.