Aspirin inhibits both lipid peroxides and thromboxane in preeclamptic placentas. 1995

Y Wang, and S W Walsh
Department of Obstetrics and Gynecology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.

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 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 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 B2 and 6-keto-PGF1 alpha, and for lipid peroxides by peroxide 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/microgram/h) and thromboxane (0.66 +/- 0.11 vs. 0.32 +/- 0.10 pg/microgram/h), but not prostacyclin (0.24 +/- 0.05 vs. 0.17 +/- 0.02 pg/microgram/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 aspirin inhibits lipid peroxides, as well as thromboxane and prostacyclin, in preeclamptic placentas. The inhibitory effects are dose dependent. Low-dose aspirin (5 x 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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008054 Lipid Peroxides Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D011225 Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Toxemias, Pregnancy,EPH Complex,EPH Gestosis,EPH Toxemias,Edema-Proteinuria-Hypertension Gestosis,Gestosis, EPH,Hypertension-Edema-Proteinuria Gestosis,Preeclampsia,Preeclampsia Eclampsia 1,Pregnancy Toxemias,Proteinuria-Edema-Hypertension Gestosis,Toxemia Of Pregnancy,1, Preeclampsia Eclampsia,1s, Preeclampsia Eclampsia,EPH Toxemia,Eclampsia 1, Preeclampsia,Eclampsia 1s, Preeclampsia,Edema Proteinuria Hypertension Gestosis,Gestosis, Edema-Proteinuria-Hypertension,Gestosis, Hypertension-Edema-Proteinuria,Gestosis, Proteinuria-Edema-Hypertension,Hypertension Edema Proteinuria Gestosis,Of Pregnancies, Toxemia,Of Pregnancy, Toxemia,Pre Eclampsia,Preeclampsia Eclampsia 1s,Pregnancies, Toxemia Of,Pregnancy Toxemia,Pregnancy, Toxemia Of,Proteinuria Edema Hypertension Gestosis,Toxemia Of Pregnancies,Toxemia, EPH,Toxemia, Pregnancy,Toxemias, EPH
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D005260 Female Females
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001241 Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5) Acetylsalicylic Acid,2-(Acetyloxy)benzoic Acid,Acetysal,Acylpyrin,Aloxiprimum,Colfarit,Dispril,Easprin,Ecotrin,Endosprin,Magnecyl,Micristin,Polopirin,Polopiryna,Solprin,Solupsan,Zorprin,Acid, Acetylsalicylic

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