An immunohistochemical examination for oxidative modification products and related enzymes was performed on the developing rat brain, because oxidative stress in the developing brain has not been fully studied. 4-hydroxy-2-nonenal-histidine (4-HNEH) and 8-hydroxy-2´-deoxyguanosine (8-OHdG) were positive in some immature neurons of the telencephalon, during embryonic stages, suggesting a unique metabolism of the fetal brain. In immature neurons of the human fetus, 4-HNEH was positive, but 8-OHdG was negative. This discrepancy between the rat and human might be derived from difference in species. Cyclooxygenase-2 and inducible nitric oxide synthase were expressed in immature neurons in the present study. These enzymes are found to be required for brain development, but their induction is known to produce reactive oxygen and nitrogen species. The accumulation of 4-HNEH and 8-OHdG may result from the induction of these enzymes, at least in part.
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