Contents lists available at ScienceDirect Archives of Biochemistry and Biophysics journal homepage: www.elsevier.com/locate/yabbi The ameliorative effect of angiotensin 1-7 on experimentally induced- preeclampsia in rats: Targeting the role of peroxisome proliferator-activated receptors gamma expression & asymmetric dimethylarginine Mervat H. El-Saka a,* , Nermin M. Madi a , Rowida Raafat Ibrahim b , Ghada Mahmoud Alghazaly c , Shereef Elshwaikh d , Manal El-Bermawy e a The Department of Physiology, Faculty of Medicine, Tanta University, Egypt b The Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Tanta University, Egypt c The Department of Internal Medicine, Faculty of Medicine, Tanta University, Egypt d The Department of Gynecology and Obstetric, Faculty of Medicine, Tanta University, Egypt e The Department of Anatomy, Faculty of Medicine, Tanta University, Egypt ARTICLE INFO Keywords: Angiotensin 1-7 Preeclampsia PPARs-γ Asymmetric dimethylarginine ABSTRACT This study was designed to explore the effect of angiotensin 1-7 (Ang 1–7) on experimentally induced-pre- eclampsia in Wistar rats targeting the role of peroxisome proliferator-activated receptors gamma expression (PPARs-γ) & asymmetric dimethylarginine (ADMA). 30 female Wistar rats were divided into three groups: Normal pregnant (NP), preeclampsia (PE), and preeclampsia treated with Ang 1–7 (PE + Ang 1–7) groups. Reduced uterine perfusion pressure (RUPP) model was induced on GD14. On GD18, protein in urine, urine volume and urinary sodium excretion were determined. On GD19, the systolic blood pressure (SBP) was mea- sured, and the gene expression of PPARs-γ were determined. The serum samples were separated for determi- nation of Ang 1–7, ADMA, soluble fms-like tyrosine kinase (sFlt-1), vascular endothelial growth factor (VEGF), nitric oxide (NO) products, endothelial nitric oxide synthase (eNOS) activity, interleukin-6 (IL-6), interleukin-10 (IL-10), malondialdehyde (MDA), and total anti-oxidant capacity (T-AOC). Compared to NP group, SBP, urine protein, serum levels of ADMA, sFlt-1, IL-6 and MDA significantly increased, while expression of PPARs-γ, serum levels of Ang 1–7, VEGF, NO products, eNOS, IL-10 and T-AOC significantly decreased in PE group, while treatment of Ang 1–7 significantly ameliorated all these studied parameters as compared to PE group. We concluded that Ang 1–7 attenuated the symptoms of preeclampsia, which might be via increasing the expression of PPARs-γ and reduction of ADMA levels which could explain its anti-hypertensive, anti-angiogenic, anti-in- flammatory and antioxidant effects. 1. Introduction Preeclampsia is one of the severe and major complications that occur during pregnancy. It commonly occurs after the 20th week of the pregnancy [1]. It can be clinically diagnosed by a new onset of in- creased systolic blood pressure (SBP) more than 140 mmHg (hy- pertension), edema and proteinuria [2]. Preeclampsia is still the main cause of fetal and maternal mortality and morbidity during the course of the pregnancy [3]. Although the exact cause of preeclampsia is not well settled, but it has been thought that the placenta might have a major role in the etiology of preeclampsia through decreased perfusion in the placenta, which may be due to defect in its blood supply [4]. The hypo-perfused placenta is characterized by production of pro- inflammatory cytokines [5], reactive oxygen species (ROS) [6] and anti-angiogenic factors as soluble fms-like tyrosine kinase (sflt-1) [7], with subsequent reduction of pro-angiogenic factors as vascular en- dothelial growth factor (VEGF) and placental growth factor (PGF) [8]. Preeclampsia can be induced by reduced uterine perfusion pressure (RUPP) [9]. RUPP has been an ideal model for studying preeclampsia in animals as it resembles the clinical picture of preeclampsia in human [10]. Despite preeclampsia is a major health problem however, no ef- fective therapy can be used to prevent or treat this disease [3]. Ter- mination of the pregnancy is the only treatment of this condition [11]. So, effective therapeutic agents have been needed for the treatment of this condition. https://doi.org/10.1016/j.abb.2019.07.006 Received 6 June 2019; Received in revised form 2 July 2019; Accepted 7 July 2019 * Corresponding author. Department of Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt. E-mail address: mervat.elsaka1@med.tanta.edu.eg (M.H. El-Saka). Archives of Biochemistry and Biophysics 671 (2019) 123–129 Available online 08 July 2019 0003-9861/ © 2019 Elsevier Inc. All rights reserved. T