R Aras-López1, J A Tovar2,3, L Martínez2,3. 1. Congenital Malformations Lab, Institute of Medicine and Molecular Genetic (INGEMM)-Institute for Health Research of La Paz Universitary Hospital (IdiPAZ), Universitary Hospital La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain. rosa.aras@hotmail.com. 2. Congenital Malformations Lab, Institute of Medicine and Molecular Genetic (INGEMM)-Institute for Health Research of La Paz Universitary Hospital (IdiPAZ), Universitary Hospital La Paz, Paseo de la Castellana 261, 28046, Madrid, Spain. 3. Department of Pediatric Surgery, Hospital Universitario La Paz, Madrid, Spain.
Abstract
PURPOSE: Congenital diaphragmatic hernia (CDH) is one of the causes of respiratory failure in newborns due to lung hypoplasia and pulmonary abnormalities leading to pulmonary hypertension (PH). NAD(P)H oxidase (Nox) is a family of isoenzymes that generate reactive oxygen species (ROS) which can contribute to PH-induced vascular dysfunction. On the other hand, superoxide dismutase (SOD) 1-2 and catalase are the antioxidant enzymes that eliminate the excess of ROS in pulmonary vascular cells. Our aim is to examine whether PH-associated with CDH is due to a dysregulation of ROS production in lungs from CDH fetuses. METHODS: Pregnant rats received either 100 mg nitrofen or vehicle on E9.5. Fetuses were recovered on E21. (1) Nox activity, (2) H2O2 production and (3) mRNA levels of Nox1, Nox2, Nox4, SOD1, SOD2 and catalase were analyzed in fetal lungs. RESULTS: Nox activity and Nox1 and Nox2 mRNA levels were increased in the lungs of fetuses with CDH. However, there were no changes in H2O2 production and Nox4 mRNA levels. SOD1, SOD2 and catalase were decreased. CONCLUSIONS: The raised oxidative stress due to increase in ROS generation by Nox isoenzymes and dysfunction of antioxidant enzymes seems to be a potential mechanism responsible on PH-associated with CDH.
PURPOSE:Congenital diaphragmatic hernia (CDH) is one of the causes of respiratory failure in newborns due to lung hypoplasia and pulmonary abnormalities leading to pulmonary hypertension (PH). NAD(P)H oxidase (Nox) is a family of isoenzymes that generate reactive oxygen species (ROS) which can contribute to PH-induced vascular dysfunction. On the other hand, superoxide dismutase (SOD) 1-2 and catalase are the antioxidant enzymes that eliminate the excess of ROS in pulmonary vascular cells. Our aim is to examine whether PH-associated with CDH is due to a dysregulation of ROS production in lungs from CDH fetuses. METHODS: Pregnant rats received either 100 mg nitrofen or vehicle on E9.5. Fetuses were recovered on E21. (1) Nox activity, (2) H2O2 production and (3) mRNA levels of Nox1, Nox2, Nox4, SOD1, SOD2 and catalase were analyzed in fetal lungs. RESULTS: Nox activity and Nox1 and Nox2 mRNA levels were increased in the lungs of fetuses with CDH. However, there were no changes in H2O2 production and Nox4 mRNA levels. SOD1, SOD2 and catalase were decreased. CONCLUSIONS: The raised oxidative stress due to increase in ROS generation by Nox isoenzymes and dysfunction of antioxidant enzymes seems to be a potential mechanism responsible on PH-associated with CDH.
Authors: Zachary Van Rheen; Cheryl Fattman; Shannon Domarski; Susan Majka; Dwight Klemm; Kurt R Stenmark; Eva Nozik-Grayck Journal: Am J Respir Cell Mol Biol Date: 2010-06-10 Impact factor: 6.914
Authors: Salome Gonzalez-Reyes; Leopoldo Martinez; Wenceslao Martinez-Calonge; Virginia Fernandez-Dumont; Juan A Tovar Journal: Biol Neonate Date: 2006-02-20
Authors: W Sluiter; A P Bos; F Silveri; R Tenbrinck; R Kraakslee; D Tibboel; J F Koster; J C Molenaar Journal: Pediatr Res Date: 1992-10 Impact factor: 3.756
Authors: Maria Del Mar Romero-Lopez; Marc Oria; Miki Watanabe-Chailland; Maria Florencia Varela; Lindsey Romick-Rosendale; Jose L Peiro Journal: Metabolites Date: 2021-03-18