ASPIRIN INHIBITS BOTH LIPID PEROXIDES AND THROMBOXANE IN PREECLAMPTICPLACENTAS

Preeclampsia is a hypertensive disorder of human pregnancy that is a l eading cause of premature delivery and fetal growth retardation. It is characterized by hypertension, reduced uteroplacental blood flow, pro teinuria, and edema. Preeclampsia is associated with an imbalance of i ncreased thromboxane and decreased prostacyclin, as well as with an im balance of increased lipid peroxides and decreased antioxidants. Low-d ose aspirin (ASA) therapy (60-150 mg/day) is being evaluated for the p revention of preeclampsia. The rationale for this is that low-dose ASA selectively inhibits thromboxane synthesis without affecting prostacy clin synthesis. We hypothesized that ASA might also inhibit the synthe sis of lipid peroxides. The purpose of this study was to examine the e ffects of aspirin on lipid peroxide, thromboxane, and prostacyclin pro duction rates in placentas obtained from women with preeclampsia. Plac entas were obtained from five preeclamptic women. Placental tissues (3 50 mg) were incubated in Dulbecco's Modified Eagles Medium (DMEM) for 48 h, alone and with varying concentrations of aspirin: 1 X 10(-6) M, 1 X 10(-5) M, 5 X 10(-5) M, 1 X 10(-4) M, and 5 X 10(-4) M. Samples we re collected at 0, 2, 6, 16, 28, and 48 h of incubation, and analyzed for thromboxane and prostacyclin by RIA of their stable metabolites, t hromboxane B-2 and 6-keto-PGF(1 alpha), and for lipid peroxides by per oxide equivalents. As compared to control, an aspirin concentration of 5 X 10(-5) M significantly inhibited (p < 0.05) both lipid peroxides (3.15 +/- 0.49 vs. 1.90 +/- 0.31 pmol/mu g/h) and thromboxane (0.66 +/ - 0.11 vs. 0.32 +/- 0.10 pg/mu g/h), but nor prostacyclin (0.24 +/- 0. 05 vs. 0.17 +/- 0.02 pg/mu g/h, p > 0.05). Lower aspirin doses (1 X 10 (-6) M, 1 X 10(-5) M) had no effect, whereas higher doses (1 X 10(-4) M and 5 X 10(-4) M) inhibited all three compounds. We conclude that as pirin inhibits lipid peroxides, as well as thromboxane and prostacycli n, in preeclamptic placentas. The inhibitory effects are dose dependen t. Low-dose aspirin (5 X 10(-5) M) selectively inhibits lipid peroxide s and thromboxane without affecting prostacyclin. We speculate that th e selective inhibitory effect of low-dose aspirin may account for its effectiveness in the prevention of preeclampsia.