Complete arrest of maternal-fetal blood supply for up to 30 min caused a time-dependent increase in the endogenous levels of
lipid peroxides (LPO) in fetal brain and
liver extracts and fetal blood and amniotic fluids as indicated by the appearance of
thiobarbituric acid reactive substances (
TBARS). A steady increase of
TBARS from 48.0 +/- 2.2 pmol/g wet weight to 75.0 +/- 5.6 pmol/g wet weight up to 30 min restriction was noticed in the fetal brain. The fetal liver
TBARS values increased by approximately 69% after 5 min restriction and remained high, above the control level, for 30 min. After two days reperfusion following 30 min restriction, the
TBARS levels in the fetal brain were 1.8 fold higher above the control, while those of the liver returned to control values. The levels of the
lipid-soluble
antioxidant alpha-tocopherol were reduced by about 40% and 50% in the placenta and brain tissues after 5 min restriction, respectively. Slices of fetal brain incubated at 37 degrees C in DMEM under
oxygen in the presence of 50 microM Fe2+ were able to generate LPO in a time- and tissue concentration-dependent manner. After 15 min incubation, about 6.3 fold increase in total
TBARS levels could be measured in the presence of 50 microM Fe2+, most of which was released in the medium. The
iron chelator desferrioxamine (25 microM) and the
antioxidant alpha-tocopherol (10 microM) added to the incubation medium, each inhibited by about 88%
TBARS production. After 20 min episode of
ischemia, fetal brain slices released into the medium 138.5 +/- 9.8 nmol/15 min/mg
DNA compared to 75.9 +/- 4.5 nmol/15 min/mg
DNA released by the
sham preparations. After 3 h reperfusion, brain slices from fetuses exposed to 20 min
ischemia continued to produce
TBARS above control levels, whereas those of brief
ischemia (5 min) returned to control levels. The data indicate that the limited resistance of the fetal brain to brief, rather than prolonged, periods of
ischemia, is likely due to a lack of free FA for LPO generation, rather than the levels of tissue
lipid antioxidants.