PLACENTAL MITOCHONDRIA AS A SOURCE OF OXIDATIVE STRESS IN PREECLAMPSIA

Pre-eclampsia is a hypertensive disorder of human pregnancy that is a leading cause of premature delivery and fetal growth retardation. It i s characterized by hypertension, reduced uteroplacental blood flow, pr oteinuria and oedema. Pre-eclampsia is associated with increased lipid peroxidation in the maternal circulation and in the placenta. Mitocho ndria are sources of oxygen radicals and are enriched with polyunsatur ated fatty acids that are susceptible to peroxidation. Therefore, the mitochondria could be an important source of oxidative stress and lipi d peroxidation. To study this, the level of lipid peroxidation in the mitochondrial fraction of placentae obtained from normally pregnant wo men (n = 8) and women with pre-eclampsia (n = 8) was examined. Placent al tissues were homogenized and the mitochondrial fraction was isolate d by ultracentrifugation. Mitochondrial lipid peroxides were estimated by malondialdehyde (MDA). NADPH and Fe++ were used to stimulate lipid peroxidation. Superoxide dismutase (SOD) was used to inhibit superoxi de radicals and mannitol to inhibit hydroxyl radicals. The following r esults were found: (1) MDA levels were significantly greater in the mi tochondrial fraction isolated from pre-eclamptic placentae than from n ormal placentae (27.4 +/- 3.0 versus 17.0 +/- 1.8 nmol/g tissue, mean +/- s.e., P<0.05); (2) the oxidative potential of the pre-eclamptic mi tochondrial fraction was also higher than normal as evidenced by the s ignificantly greater stimulation of lipid peroxidation by NADPH and Fe ++ (248 +/- 25 versus 164 +/- 35 nmol/g, P<0.05); (3) superoxide dismu tase, but not mannitol, attenuated the lipid peroxidation induced by N ADPH and Fe++ demonstrating that superoxide is the radical responsible for mitochondrial lipid peroxidation in this system; and (4) the amou nt of mitochondrial protein was 47 per cent greater and the activity o f the mitochondrial enzyme, citrate synthase, was 56 per cent greater in the pre-eclamptic placentae indicating an increase in the amount of mitochondria in the pre-eclamptic placentae. It is concluded that: (1 ) mitochondrial lipid peroxidation is increased in pre-eclampsia; (2) the amount of placental mitochondria is increased in pre-eclampsia; (3 ) placental mitochondria contribute to the abnormal increase in lipid peroxidation that occurs in pre-eclamptic placentae by both an increas e in their amount and an increase in their susceptibility to oxidation ; and (4) mitochondrial generation of superoxide could be an important source of oxidative stress in pre-eclampsia. (C) 1998 W. B. Saunders Company Ltd.