Aspirin inhibits both lipid peroxides and thromboxane in preeclamptic placentas

Abstract

Preeclampsia is a hypertensive disorder of human pregnancy that is a leading cause of premature delivery and fetal growth retardation. It is characterized by hypertension, reduced uteroplacental blood flow, proteinuria, and edema. Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin, as well as with an imbalance of increased lipid peroxides and decreased antioxidants. Low-dose aspirin (ASA) therapy (60–150 mg/day) is being evaluated for the prevention of preeclampsia. The rationale for this is that low-dose ASA selectively inhibits thromboxane synthesis without affecting prostacyclin synthesis. We hypothesized that ASA might also inhibit the synthesis of lipid peroxides. The purpose of this study was to examine the effects of aspirin on lipid peroxide, thromboxane, and prostacyclin production rates in placentas obtained from women with preeclampsia. Placentas were obtained from five preeclamptic women. Placental tissues (350 mg) were incubated in Dulbecco's Modified Eagles Medium (DMEM) for 48 h, alone and with varying concentrations of aspirin: 1 × 10 −6 M, 1 × 10 −5 M, 5 × 10 −5 M, 1 × 10 −4 M, and 5 × 10 4 M. Samples were collected at 0, 2, 6, 16, 28, and 48 h of incubation, and analyzed for thromboxane and prostacyclin by RIA of their stable metabolites, thromboxane B 2 and 6-keto-PGF 1α, and for lipid peroxides by peroxide equivalents. As compared to control, an aspirin concentration of 5 × 10 −5 M significantly inhibited ( p < 0.05) both lipid peroxides (3.15 ± 0.49 vs. 1.90 ± 0.31 pmol/μg/h) and thromboxane (0.66 ± 0.11 vs. 0.32 ± 0.10 pg/μg/h), but not prostacyclin (0.24 ± 0.05 vs. 0.17 ± 0.02 pg/μg/h, p > 0.05). Lower aspirin doses (1 × 10 6 M, 1 × 10 −5 M) had no effect, whereas higher doses (1 × 10 −4 M and 5 × 10 −4 M) inhibited all three compounds. We conclude that aspirin inhibits lipid peroxides, as well as thromboxane and prostacyclin, in preeclamptic placentas. The inhibitory effects are dose dependent. Low-dose aspirin (5 × 10 −5 M) selectively inhibits lipid peroxides and thromboxane without affecting prostacyclin. We speculate that the selective inhibitory effect of low-dose aspirin may account for its effectiveness in the prevention of preeclampsia.