Effects of deferoxamine, a chelator of free iron, on Na+,K+-ATPase activity of cortical brain cell membrane during early reperfusion after hypoxia-ischemia in newborn lambs

Floris Groenendaal, Madjida Shadid, Jane E. McGowan, Om P. Mishra, Frank Van Bel

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Abstract

Free iron chelation after hypoxia-ischemia can reduce free radical-induced damage to brain cell membranes and preserve electrical brain activity. We investigated whether chelation of free iron with deferoxamine (DFO) preserved cortical cell membrane activity of Na+,K+-ATPase and electrocortical brain activity (ECBA) of newborn lambs during early reperfusion after severe hypoxia-ischemia. Hypoxia was induced in 16 lambs by decreasing the fraction of inspired oxygen to 0.07 for 30 min, followed by a 5-min period of hypotension (mean arterial blood pressure +,K+-ATPase activity was measured in the P2 fraction of cortical tissue. Na+,K+-ATPase activity was 35.1 ± 7.4, 42.0 ± 7.6, and 40.7 ± 1.4 μmol inorganic phosphate/mg protein per hour in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p <0.05: DFO versus PLAC). ECBA was 11.2 ± 6.1, 14.8 ± 4.8, and 17.5±.0.5 μV in PLAC-treated, DFO-treated, and sham-operated lambs, respectively (p = 0.06: DFO versus PLAC). Na+,K+-ATPase activity correlated with ECBA at 180 min of reperfusion (r = 0.85, p <0.001). We conclude that Na+,K+-ATPase activity of cortical brain tissue was higher in DFO-treated lambs compared with PLAC-treated animals during the early reperfusion phase after severe hypoxiaischemia, suggesting a reduction of free radical formation by DFO. Furthermore, a positive relationship was found between Na+,K+-ATPase activity and ECBA.

Original languageEnglish (US)
Pages (from-to)560-564
Number of pages5
JournalPediatric Research
Volume48
Issue number4
StatePublished - 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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