Abstract 11586: Therapeutic Potential of Alpha Lipoic Acid in a Rat Model of Superimposed Preeclampsia: Effect on Maternal Signs, Placental Development and Fetal Growth

IntroductionSuperimposed preeclampsia (SPE) occurs in 25-40% of pregnant women affected by chronic hypertension and is associated with adverse maternal and neonatal outcomes. In previous studies, we have demonstrated that pregnant Stroke-prone Spontaneously Hypertensive Rat represent a spontaneous S...

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Published in:Circulation (New York, N.Y.) Vol. 146; no. Suppl_1; p. A11586
Main Authors: Barrientos, Gabriela, Incardona, Claudio A, Giardina, Graciela, Uceda, Ana M, Sgariglia, Ma Alejandra, Galleano, Monica, Garcia, Silvia I
Format: Journal Article
Language:English
Published: Lippincott Williams & Wilkins 08-11-2022
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Summary:IntroductionSuperimposed preeclampsia (SPE) occurs in 25-40% of pregnant women affected by chronic hypertension and is associated with adverse maternal and neonatal outcomes. In previous studies, we have demonstrated that pregnant Stroke-prone Spontaneously Hypertensive Rat represent a spontaneous SPE model, characterized by defective trophoblast invasion and placental oxidative stress, asymmetric fetal growth restriction and worsening maternal hypertension with renal dysfunction towards term. Here, we sought to evaluate the therapeutic potential of alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy in this model. MethodsCongenic timed breedings were established using SHRSP and Wistar Kyoto (WKY) females (10-12 weeks old, 200-250 g body weight, N = 10 animals/day analyzed). Upon vaginal plug detection (gestation day (GD)1), dams were assigned to two groupsALA treatment, injected 25mg/kg body weight ALA i.p. on GD1, GD8 and GD12 and controls, receiving saline following the same protocol. Systolic blood pressure (SBP) profiles throughout pregnancy were recorded using a noninvasive volume pressure recording device. On GD20, animals were euthanized and fetoplacental specimens isolated for morphological and molecular analyzes. Statistical analysis was run on GraphPad Prism v 8.0, using 2 way ANOVA. Statistical significance was set at p˂ 0.05. ResultsTreatment with ALA prevented the pregnancy-dependent SBP increase typical of the SHRSP model (SBP GD14 SHRSP169.3±2.1 mmHg vs. SHRSP+ALA146.1±3.4, p˂0.001). Furthermore, fetuses carried by ALA-treated SHRSP displayed increased weights (SHRSP1.75±0.05g vs. SHRSP+ALA1.99±0.01g, p˂0.05) and decreased cephalization indexes on GD20, indicating an improvement in the asymmetric growth restriction pattern. Treated dams also presented increased numbers of glycogen trophoblasts (PAS+ cells) in the junctional zone and an enhanced vessel density on Isolectin B4+ staining, suggesting an improved placental function. ConclusionsALA administration during early pregnancy in the SHRSP model ameliorated maternal signs and improved placental function and fetal growth, emerging as a novel therapeutic intervention in pregnancies affected by chronic hypertension
ISSN:0009-7322
1524-4539
DOI:10.1161/circ.146.suppl_1.11586