TY - JOUR
T1 - Oxidative and Inflammatory Imbalance in Placenta and Kidney of sFlt1-Induced Early-Onset Preeclampsia Rat Model
AU - Santana-Garrido, Álvaro
AU - Reyes-Goya, Claudia
AU - Espinosa-Martín, Pablo
AU - Sobrevia, Luis
AU - Beltrán, Luis M.
AU - Vázquez, Carmen M.
AU - Mate, Alfonso
N1 - Funding Information:
This research was funded by Consejería de Salud, Junta de Andalucía (PI-0456-2018); Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía (2020/275 and 2021/188; CTS-584). Á.S.-G. is recipient of an FPU predoctoral fellowship from Ministerio de Universidades (FPU17/03465). C.R.-G. and P.E.-M. were supported by Ministerio de Ciencia e Innovación, Ayudas para la Promoción de Empleo Joven e Implantación de la Garantía Juvenil en I+D+i 2017-2020 (PEJ2018-004474-A and PEJ5-2020-662, respectively). L.S. is funded by the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT, grant number 1190316), Chile; International Sabbaticals (University Medical Centre Groningen, University of Groningen, The Netherlands) from the Vice rectorate of Academic Affairs, Academic Development Office of the Pontificia Universidad Católica de Chile; and the Thematic Project-Diamater, São Paulo Research Foundation (FAPESP, grant number 16/01743-5), Brazil.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - inflammation
KW - kidney
KW - NADPH oxidase
KW - nitric oxide
KW - oxidative stress
KW - placenta
KW - preeclampsia
KW - sFlt1
U2 - 10.3390/antiox11081608
DO - 10.3390/antiox11081608
M3 - Article
AN - SCOPUS:85137354426
SN - 2076-3921
VL - 11
JO - Antioxidants
JF - Antioxidants
IS - 8
M1 - 1608
ER -