Oxygen free radical generation during in-utero hypoxia in the fetal guineapig brain: the effects of maturity and of magnesium sulfate administration

Previous studies have shown, employing direct measurements with electron sp in resonance (ESR) spectroscopy, that hypoxia induces an increased producti on of oxygen free radicals (OFR) in the brain of the guinea pig fetus. The present study using the same approach, investigated the effects of maturity and Mg2+-pretreatment on hypoxia-induced OFR formation in the guinea pig f etal brain. The normoxic and the hypoxic groups were exposed for 60 min to 21% or 7% oxygen, respectively. The control group consisted of term fetuses exposed to normoxia (n = 7) and hypoxia (n = 7). The experimental groups c onsisted of the following: (a) for the investigation on maturity effect, pr eterm fetuses (40 days) exposed to normoxia (n = 6) or hypoxia (n = 6); and (b) for the Mg2+-pretreatment investigation, term fetuses (60 days) expose d to normoxia (n = 6) or hypoxia (n = 6) following maternal pretreatment wi th Mg2+ which consisted of an initial bolus of MgSO4 (600 mg/kg, i.p.) 1 h prior to hypoxia followed by a second dose (300 mg/kg, i.p.). Oxygen free r adicals were measured by ESR spectroscopy in the fetal cerebral cortical ti ssue utilizing phenyl-N-tert-butylnitrone (PBN) spin trapping. Fetal brain tissue hypoxia was documented biochemically by decreased tissue levels of A TP and phosphocreatine. In the control group of term fetuses, the cortical tissue from hypoxic fetuses showed a significant increase in spin adducts ( 71% increase, p < 0.01). In the preterm group, the cortical tissue from hyp oxic fetuses showed a 33% increase in spin adducts (p < 0.001). The baselin e free radical generation during normoxia was 22.5% higher at preterm than at term (41.4 +/- 3.5 units/g issue vs. 33.8 +/- 9.3 units/g tissue, p < 0. 05). In Mg2+-treated groups, spin adduct levels in cortical tissue from hyp oxic fetuses did not significantly differ from those of the normoxic group (30.2 +/- 9.9 units/g tissue, normoxic-Mg2+ vs. 30.6 +/- 8.1 units/g tissue , hypoxic-Mg2+). The results indicate that the fetal brain at term may be m ore susceptible to hypoxia-induced free radical damage than at preterm and that Mg2+ administration significantly decreased the hypoxia-induced increa se in oxygen free radical generation in the term fetal guinea pig brain in comparison with non-treated hypoxic group. (C) 1999 Elsevier Science B.V. A ll rights reserved.