TY - JOUR
T1 - 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
AU - Groenendaal, Floris
AU - Shadid, Madjida
AU - McGowan, Jane E.
AU - Mishra, Om P.
AU - Van Bel, Frank
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11004251
AN - SCOPUS:0033794991
SN - 0031-3998
VL - 48
SP - 560
EP - 564
JO - Pediatric Research
JF - Pediatric Research
IS - 4
ER -