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Published on: October 19, 2013
Omeprazole does not Potentiate Acute Oxygen Toxicity in Fetal Human Pulmonary Microvascular Endothelial Cells Exposed
Ananddeep Patel1, Shaojie Zhang1, Bhagavatula Moorthy1
1Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Insights
Omeprazole does not worsen hyperoxia-induced lung injury in human fetal cells. This study found omeprazole did not increase cytotoxicity or ROS in pulmonary microvascular endothelial cells under hyperoxia.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Neonatology
Background:
- Bronchopulmonary dysplasia (BPD) involves impaired lung development in premature infants, exacerbated by hyperoxia.
- Omeprazole (OM), a proton pump inhibitor, previously showed protective effects against hyperoxia in adult models but potentially harmful effects in newborn mice.
Purpose of the Study:
- To investigate if omeprazole potentiates hyperoxia-induced cytotoxicity and reactive oxygen species (ROS) generation in primary human pulmonary microvascular endothelial cells (HPMEC) derived from fetal lungs.
Main Methods:
- Human pulmonary microvascular endothelial cells (HPMEC) were treated with omeprazole (OM) and exposed to hyperoxia or air.
- Assessed aryl hydrocarbon receptor (AhR) activation via CYP1A1 mRNA and NQO1 expression.
- Measured cytotoxicity and hydrogen peroxide (H₂O₂) levels.
Main Results:
- Omeprazole activated AhR and increased NQO1 expression, but hyperoxia decreased NQO1 protein in OM-treated cells.
- Hyperoxia increased cytotoxicity and H₂O₂ levels, but OM did not further augment these effects.
- Hyperoxia-induced oxygen toxicity was similar in both vehicle- and OM-treated cells.
Conclusions:
- Omeprazole does not potentiate acute hyperoxic injury in human pulmonary microvascular endothelial cells in vitro.
- Findings contradict the hypothesis and suggest OM may not exacerbate hyperoxia-related lung injury in this specific cellular model.
Abstract:
Hyperoxia contributes to the pathogenesis of broncho-pulmonary dysplasia (BPD), which is a developmental lung disease of premature infants that is characterized by an interruption of lung alveolar and pulmonary vascular development. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Earlier we observed that OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury in adult mice and oxygen toxicity in adult human lung cells. However, our later studies in newborn mice demonstrated that OM potentiates hyperoxia-induced developmental lung injury. Whether OM exerts a similar toxicity in primary human fetal lung cells is unknown. Hence, we tested the hypothesis that OM potentiates hyperoxia-induced cytotoxicity and ROS generation in the human fetal lung derived primary human pulmonary microvascular endothelial cells (HPMEC). OM activated AhR as evident by a dose-dependent increase in cytochrome P450 (CYP) 1A1 mRNA levels in OM-treated cells. Furthermore, OM at a concentration of 100 μM (OM 100) increased NADP(H) quinone oxidoreductase 1 (NQO1) expression. Surprisingly, hyperoxia decreased rather than increase the NQO1 protein levels in OM 100-treated cells. Exposure to hyperoxia increased cytotoxicity and hydrogen peroxide (H2O2) levels. Interestingly, OM 100-treated cells exposed to air had increased H2O2 levels. However, hyperoxia did not further augment H2O2 levels in OM 100-treated cells. Additionally, hyperoxia-mediated oxygen toxicity was similar in both vehicle- and OM-treated cells. These findings contradict our hypothesis and support the hypothesis that OM does not potentiate acute hyperoxic injury in HPMEC in vitro.
