Superoxide dismutase, glutathione peroxidase and lipoperoxidation in Down's syndrome fetal brain.

Certain aspects of the metabolism of oxygen derivatives were investigated in the cerebral cortex from Down's syndrome (trisomy 21) fetuses. In comparison with controls of similar gestational age, the specific activity of the cytosolic Cu/Zn-dependent superoxide dismutase (SOD-I) was significantly elevated by 60 +/- 5%. This is consistent with a gene dosage effect, as the gene coding for SOD-I is on chromosome 21. In order to determine whether the increase in SOD-I activity is associated with an adaptive rise in glutathione peroxidase (GSHPx), as has been observed in other tissues, the activity of this enzyme was also estimated but was found not to be altered in the Down's syndrome brain. In addition, in vitro lipoperoxidation, estimated by the formation of malondialdehyde (MDA) on incubation of homogenates fortified with ascorbate and Fe2+, was significantly elevated (36 +/- 4%) in cerebral cortex of the Down's syndrome fetuses. The concentration of total combined polyunsaturated fatty acids (PUFA) was not significantly altered in the tissue, although there is evidence for differences in the composition of certain phospholipids. It is proposed that, on account of the evidence for a potential perturbation of oxygen free radical metabolism (notably an increased SOD-I activity not compensated by a rise in GSHPx) and for enhanced in vitro peroxidizability of PUFA, there may be increased lipoperoxidative damage in the Down's syndrome brain prenatally.