S W Walsh1, Y Wang, H H Kay, M C McCoy. 1. Department of Obstetrics and Gynecology, Medical College of Virginia, Richmond 23298-0034.
Abstract
OBJECTIVE: Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin and an abnormal increase of lipid peroxides. Lipid peroxides are toxic compounds that damage cells and inhibit prostacyclin synthesis. Low-dose aspirin therapy reduces the incidence of preeclampsia, presumably by selective inhibition of thromboxane to restore a balance between thromboxane and prostacyclin. However, the effectiveness of low-dose aspirin might also relate to inhibition of lipid peroxides. STUDY DESIGN: To test this hypothesis, 10 women at risk of preeclampsia were placed on low-dose aspirin therapy (81 mg/day) between 9 and 34 weeks of gestation. Plasma samples were collected before and after 3 to 4 days and 3 to 4 weeks of aspirin therapy. Samples were analyzed for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, and for lipid peroxides by hydrogen peroxide equivalents. RESULTS: Low-dose aspirin significantly decreased (p < 0.05) both lipid peroxides (130 +/- 18 vs 92 +/- 11 and 68 +/- 9 nmol/ml, mean +/- SE) and thromboxane (502 +/- 67 vs 138 +/- 67 and 8 +/- 5 pg/ml), but it did not affect prostacyclin (55 +/- 10 vs 41 +/- 8 and 40 +/- 11 pg/ml, p > 0.1). CONCLUSION: Low-dose aspirin selectively inhibits both lipid peroxides and thromboxane without affecting prostacyclin. Inhibition of both lipid peroxides and thromboxane by low-dose aspirin reveals a new mechanism of action and may account for its effectiveness in the prevention of preeclampsia.
OBJECTIVE: Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin and an abnormal increase of lipid peroxides. Lipid peroxides are toxic compounds that damage cells and inhibit prostacyclin synthesis. Low-dose aspirin therapy reduces the incidence of preeclampsia, presumably by selective inhibition of thromboxane to restore a balance between thromboxane and prostacyclin. However, the effectiveness of low-dose aspirin might also relate to inhibition of lipid peroxides. STUDY DESIGN: To test this hypothesis, 10 women at risk of preeclampsia were placed on low-dose aspirin therapy (81 mg/day) between 9 and 34 weeks of gestation. Plasma samples were collected before and after 3 to 4 days and 3 to 4 weeks of aspirin therapy. Samples were analyzed for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, and for lipid peroxides by hydrogen peroxide equivalents. RESULTS: Low-dose aspirin significantly decreased (p < 0.05) both lipid peroxides (130 +/- 18 vs 92 +/- 11 and 68 +/- 9 nmol/ml, mean +/- SE) and thromboxane (502 +/- 67 vs 138 +/- 67 and 8 +/- 5 pg/ml), but it did not affect prostacyclin (55 +/- 10 vs 41 +/- 8 and 40 +/- 11 pg/ml, p > 0.1). CONCLUSION: Low-dose aspirin selectively inhibits both lipid peroxides and thromboxane without affecting prostacyclin. Inhibition of both lipid peroxides and thromboxane by low-dose aspirin reveals a new mechanism of action and may account for its effectiveness in the prevention of preeclampsia.
Authors: Scott W Walsh; Daniel T Reep; S M Khorshed Alam; Sonya L Washington; Marwah Al Dulaimi; Stephanie M Lee; Edward H Springel; Jerome F Strauss; Daniel J Stephenson; Charles E Chalfant Journal: Reprod Sci Date: 2020-06-17 Impact factor: 3.060