2. Academic Validation
  3. Oxidative and Inflammatory Imbalance in Placenta and Kidney of sFlt1-Induced Early-Onset Preeclampsia Rat Model

Oxidative and Inflammatory Imbalance in Placenta and Kidney of sFlt1-Induced Early-Onset Preeclampsia Rat Model

  • Antioxidants (Basel). 2022 Aug 19;11(8):1608. doi: 10.3390/antiox11081608.
Álvaro Santana-Garrido 1 2,  Claudia Reyes-Goya 1,  Pablo Espinosa-Martín 1,  Luis Sobrevia 1 3 4 5 6 7,  Luis M Beltrán 2 8,  Carmen M Vázquez 1 2,  Alfonso Mate 1 2
Affiliations

Affiliations

  • 1 Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
  • 2 Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain.
  • 3 Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
  • 4 Medical School (Faculty of Medicine), São Paulo State University (UNESP), São Paulo 01049-010, Brazil.
  • 5 University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia.
  • 6 Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), 9713 GZ Groningen, The Netherlands.
  • 7 Tecnológico de Monterrey, Eutra, The Institute for Obesity Research (IOR), School of Medicine and Health Sciences, Monterrey 64710, Nuevo León, Mexico.
  • 8 Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain.
PMID: 36009326 DOI: 10.3390/antiox11081608
Abstract

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the new onset of hypertension plus proteinuria and/or end-organ dysfunction. Here, we investigate the role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system as a major component of Reactive Oxygen Species generation, in a rodent model of early-onset preeclampsia induced by excess sFlt1 (soluble fms-like tyrosine kinase 1). Placenta and kidney samples were obtained from normal pregnant and PE rats to measure the sFlt1/PLGF (placental growth factor) ratio in addition to oxidative stress-related parameters, including the activities and expressions of NADPH Oxidase isoforms (NOX1, NOX2, and NOX4), components of nitric oxide (NO) metabolism, and antioxidant Enzymes. Peroxisome proliferator-activated receptors (PPARα, PPARγ) and cytokines IL1β, IL3, IL6, IL10, and IL18 were also measured to evaluate the inflammation status in our experimental setting. Excessive O2●- production was found in rats that were treated with sFlt1; interestingly, this alteration appears to be mediated mainly by NOX2 in the placenta and by NOX4 in the kidney. Altered NO metabolism and antioxidant defense systems, together with mitochondrial dysfunction, were observed in this model of PE. Preeclamptic Animals also exhibited overexpression of proinflammatory biomarkers as well as increased Collagen deposition. Our results highlight the role of NADPH Oxidase in mediating oxidative stress and possibly inflammatory processes in the placenta and kidney of an sFlt1-based model of early-onset preeclampsia.

Keywords

NADPH oxidase; inflammation; kidney; nitric oxide; oxidative stress; placenta; preeclampsia; sFlt1.

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