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Possible role of increased oxidative stress in pulmonary hypertension in experimental diaphragmatic hernia

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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.

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Acknowledgments

We thank Dr Mercedes Salaices of Pharmacology Department from Autónoma University of Madrid for her assistance in measuring Nox activity and H2O2 production.

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Authors and Affiliations

  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

    R. Aras-López, J. A. Tovar & L. Martínez

  2. Department of Pediatric Surgery, Hospital Universitario La Paz, Madrid, Spain

    J. A. Tovar & L. Martínez

Authors
  1. R. Aras-López
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  2. J. A. Tovar
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  3. L. Martínez
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Corresponding author

Correspondence to R. Aras-López.

Additional information

This work was supported by a grant from the RETICS program from the Instituto de Salud Carlos III (RD12/0026/0011) and FEDER funds from the EU.

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Aras-López, R., Tovar, J.A. & Martínez, L. Possible role of increased oxidative stress in pulmonary hypertension in experimental diaphragmatic hernia. Pediatr Surg Int 32, 141–145 (2016). https://doi.org/10.1007/s00383-015-3826-5

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  • DOI: https://doi.org/10.1007/s00383-015-3826-5

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